- Positive Phase 3 data in 2nd/3rd line NSCLC (Dublin-3): Superior efficacy benefit in plinabulin and docetaxel combination in overall survival, 2-year and 3-year OS rate, PFS, ORR, and significant reduction of grade 4 neutropenia vs. docetaxel alone
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BeyondSpring Announces Third Quarter 2021 Financial Results and Provides a Corporate Update
Company now expects to release topline 52-week results from MAESTRO-NAFLD-1 in January 2022 Company now expects to release topline 52-week results from MAESTRO-NAFLD-1 in January 2022
WOBURN, Mass., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Biofrontera Inc. (Nasdaq: BFRI), a biopharmaceutical company specializing in the commercialization of dermatological products, announced that through the exercise of outstanding warrants the majority ownership of Biofrontera AG was diluted below 50%. Biofrontera AG’s shareholding in Biofrontera Inc. of 8,000,000 shares is unchanged, but now represents approximately 47% of the currently outstanding shares. As a result, Biofrontera Inc. is no longer considered a subsidiary of Biofrontera AG. Biofrontera Inc.’s common stock and warrants are traded on the Nasdaq Capital Market under the ticker symbols “BFRI” and “BFRIW,” respectively.
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Biofrontera Inc. announces reduction of Biofrontera AG shareholding to less than 50% through warrant exercises
MALVERN, Pa., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Ocugen, Inc. (Nasdaq: OCGN), a biopharmaceutical company focused on discovering, developing, and commercializing novel therapeutics and vaccines, announced today that its partner, Bharat Biotech, posted results from a Phase 2/3 trial conducted in India of candidate vaccine, COVAXIN™ (BBV152), in children, aged 2 – 18 years, demonstrating a robust neutralizing antibody response and favorable safety profile on the pre-print server, medRXiv. Using a two-dose regimen administered 28-days apart, antibody responses in subjects were comparable to adult data from a previous phase 3 study. Those results demonstrated a greater than 93% reduction in severe disease. These pediatric data were the basis of Ocugen’s pediatric Emergency Use Authorization (EUA) submission in the United States for children 2-18 on November 5, 2021.
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Ocugen Partner, Bharat Biotech, Announces Positive Immunogenicity and Safety Data From COVAXIN™ (BBV152), COVID-19 Candidate Vaccine, in Children 2...
Company announcement – No. 78 / 2021
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Total number of shares and voting rights in Zealand Pharma at December 30, 2021
NEW YORK and LONDON, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX) (“Akari” or the “Company”), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, today announced that it has entered into definitive agreements with institutional investors and accredited investors, led by existing investors of the Company, including Dr. Ray Prudo, the Company’s Chairman, to receive gross proceeds of approximately $6.0 million.
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Akari Therapeutics, Plc Announces $6.0 Million Registered Direct Offering
THE WOODLANDS, Texas, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that it has submitted a New Drug Application to the U.S. Food and Drug Administration seeking approval for the marketing and sale of sotagliflozin to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure irrespective of left ventricular ejection fraction. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.
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Lexicon Submits New Drug Application for Sotagliflozin for the Treatment of Heart Failure in Adults With Type 2 Diabetes
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Mesoblast Provides Update Following Meeting With FDA’s OTAT on Remestemcel-L for Children With Acute Graft Versus Host Disease
HALIFAX, Nova Scotia, Dec. 30, 2021 (GLOBE NEWSWIRE) -- MedMira Inc. (MedMira) (TSXV: MIR), reported today on its financial results for the quarter ended October 31, 2021.
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MedMira Reports First Quarter Results FY2022
DURHAM, N.C., Dec. 31, 2021 (GLOBE NEWSWIRE) -- Humacyte, Inc. (Nasdaq: HUMA), a clinical-stage biotechnology platform company developing universally implantable bioengineered human tissue at commercial scale, today announced the appointment of Surgical Key Opinion Leaders (KOLs) Alan P. Kypson, M.D., FACS; Luigi Pascarella, M.D., FACS; and Todd E. Rasmussen, M.D., FACS, (Col, ret. USAF MC), to new advisory positions. In these roles, the KOLs will lend their expertise and support to guide the education and clinical advancement efforts of the Human Acellular VesselTM (HAV) and help identify opportunities to advance the Company's early stage complex tissue constructs pipeline and platform.
The Phase 1 Study Will be Comprised of Two Parts: Phase 1a Dose-escalation that will Evaluate the Safety and Tolerability of NXP800 in Patients with Advanced Solid Tumors, Followed by a Phase 1b to Evaluate Preliminary Efficacy in Specific Populations The Phase 1 Study Will be Comprised of Two Parts: Phase 1a Dose-escalation that will Evaluate the Safety and Tolerability of NXP800 in Patients with Advanced Solid Tumors, Followed by a Phase 1b to Evaluate Preliminary Efficacy in Specific Populations
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Nuvectis Pharma Initiates Phase 1 Clinical Trial of NXP800
– Growing body of evidence validates Vir’s approach of targeting a highly conserved region of the spike protein –
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Vir Biotechnology Announces New Research Describing the Structural Basis of SARS-CoV-2 Omicron Immune Evasion and Receptor Engagement
VANCOUVER, British Columbia, Dec. 31, 2021 (GLOBE NEWSWIRE) -- Franciosi Consulting Ltd. is currently tracking the number of falls involving seniors and that have been reported in the public domain during this COVID-19 pandemic. In particular, government sites such as the Canadian Institute for Health Information, online media reports and survey portals from various countries are being searched to determine these numbers as well as the nature and location of the falls in designated senior housing such as long term care, assisted living and independent living. Lui Franciosi states, “During this pandemic, seniors have likely not had the same level of exercise and therefore their body core strength is not as optimal to prevent injury. It is known that falls are the leading cause of injuries among seniors, accounting for 61 per cent of injury-related deaths and 81 per cent of injury-related hospitalizations in Canada. There are close to 5,000 deaths each year linked to seniors’ falls and nearly 100,000 hospitalizations.” The aim of this work is to better understand how many of these falls are actually predictable and whether an algorithm could be developed to help healthcare staff and families prevent falls, especially in frequent fallers.
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Lui Franciosi Tracking Published Fall Numbers of Seniors During this COVID-19 Pandemic
TORONTO, Dec. 31, 2021 (GLOBE NEWSWIRE) -- Cronos Group Inc. (NASDAQ: CRON) (TSX: CRON) (“Cronos Group” or the “Company”) is providing a default status report in accordance with the alternative information guidelines set out in National Policy 12-203 – Management Cease Trade Orders (“NP 12-203”).
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Cronos Group Provides Bi-Weekly MCTO Status Update
Continuing Education Activity
Bone marrow transplant, also known as hematopoietic stem cell transplant (HPSCT) involves the administration of healthy hematopoietic stem cells to patients with dysfunctional or depleted bone marrow. This helps to augment bone marrow function and, depending on the disease being treated, leads to either destruction of malignant tumor cells or to generation of functional cells that can replace the dysfunctional ones, as is the case of immune-deficiency syndromes, hemoglobinopathies, and other diseases. This activity reviews the indications, contraindications, and complications associated with hematopoietic stem cell transplants and highlights the role of the interprofessional team in the management of patients requiring this treatment.
Objectives:
Describe the indications for hematopoietic stem cell transplants.
Review the contraindications to hematopoietic stem cell transplants.
Outline the potential complications of hematopoietic stem cell transplants.
Describe the need for a well-integrated, interprofessional team approach to improve care for patients undergoing hematopoietic stem cell transplants.
Bone marrow transplant (hematopoietic stem cell transplant) (HPSCT) involves the administration of healthy hematopoietic stem cells in patients with dysfunctional or depleted bone marrow. This helps to augment bone marrow function and allows, depending on the disease being treated, to either destroy tumor cells with malignancy or to generate functional cells that can replace the dysfunctional ones in cases like immune deficiency syndromes, hemoglobinopathies, and other diseases.
History and Evolution
Hematopoietic stem cell transplantation (HSCT) was first explored in humans in the 1950s and was based on observational studies in mice models which showed that infusion of healthy bone marrow components into a myelosuppressed bone marrow could induce recovery of its function in the recipient.[1]These animal-based studies soon found their clinical application into humans when the first successful bone marrow transplant was performed in monozygotic twins in New York in 1957 (syngeneic transplant) in a patient with acute leukemia.[2]As a result, the physician Dr. Thomas who performed the procedure continued his research on the development of bone marrow transplantation and later received the Nobel Prize of physiology and medicine in appreciation of his work. The first successfulallogeneicbone marrow transplant was reported in Minnesota in 1968 for a pediatric patient with severe, combined immunodeficiency syndrome.[3]Since then, allogeneic and autologous stem cell transplant has increased in the United States and worldwide. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported over 8000 allogenic transplants performed in the United States in 2016 with a higher number of autologous transplants with a steady and higher increase of autologous compared to allogenic.[4]
Definitions
Major Histocompatibility Complex (MHC)
The group of genes on the short arm of chromosome 6 (p6) that encodes human leukocyte antigens (HLA) which are considered being highly polymorphic leading to a large difference in the resultant expressed proteins on human cells. They are divided into MHC I and MHC II
Human Leukocyte Antigens (HLA)
These are the proteins expressed on the cellular surface and play an important role in alloimmunity. HLA can be divided into (HLA-A, B, and C) which are encoded by class I MHC and are expressed on all cell types and present peptides derived from the cytoplasm and are recognized by CD8+ T cells. The other HLA type is classified as (HLA- DP, DQ, and DR) which are encoded by MHC II and can be found on antigen-presenting cells (APCs) and this class is recognized by CD4+ T cells.
Syngeneic Bone Marrow Transplantation
The donor and the recipient are identical twins. The advantages include no graft versus host disease (GVHD) and no graft failure. However, only a tiny number of transplant patients will have the ability to have an identical twin for transplantation.
Autologous Bone Marrow Transplantation
The bone marrow products are collected from the patient and are reinfused after purification methods. The advantages include no GVHD. The disadvantage is that the bone marrow products may contain abnormal cells that can cause relapse in the case of malignancy hence; theoretically, this method cannot be used in all cases of abnormal bone marrow diseases.
Allogenic Transplantation
The donor is an HLA matched family member, unrelated matched donor or mismatched family donors (haploidentical).
Engraftment
The process of which infused transplanted hematopoietic stem cells produce mature progeny in the peripheral circulation
Preparative Regimen
This is a regimen that comprises high-dose chemotherapy and/or total body irradiation (TBI) which are administered to the recipient prior to stem cell infusion to eliminate the largest number of malignant cells and to allow for immunosuppression in the recipient so that engraftment can occur.
Malignant Disease
Multiple Myeloma
Autologous stem cell transplant accounts for most hematopoietic stem cell transplants according to CIBMTR in 2016 in the United States. Studies have shown increased overall survival and progression free survival in patients younger than 65 years old when consolidation therapy with melphalan is initiated followed by autologous stem cell transplantation and lenalidomide maintenance therapy.[5]The study showed a favorable outcome of high-dose melphalan plus stem-cell transplantation when compared with consolidation therapy with melphalan, prednisone, lenalidomide (MPR). It also showed a better outcome in patients who received a maintenance therapy with lenalidomide.
Hodgkin and Non-Hodgkin Lymphoma
Studies have shown that chemotherapy followed by autologous stem cell transplantation in cases of recurrent lymphomas (HL and NHL) that do not respond to initial conventional chemotherapy have better outcomes. A randomized controlled trial by Schmitz N et al. showed a better 3-year outcome of high-dose chemotherapy with autologous stem cell transplant compared to aggressive conventional chemotherapy in relapsed chemosensitive Hodgkin lymphoma. However, the overall survival was not significantlydifferent between the two groups.[6]The number of hematopoietic stem cell transplant recipient comes second after multiple myeloma according to CIBMTR.
Acute Myeloid Leukemia
Allogenic stem cell transplant has shown to improve outcome in patients with AML who fail primary induction therapy and do not achieve compete response and may prolong overall survival.[7]The study recommended that early HLA typing for patients with AML can help if they fail induction therapy and are considered for bone marrow transplant.
Acute Lymphocytic Leukemia
Allogenic stem cell transplant is indicated in refractory and resistant cases when induction therapy fails for a second time in inducing remission. Some studies suggest an increased benefit of allogenic hematopoietic stem cell transplant in patients with high risk ALL including patients with Philadelphia chromosome and those with t(4, 11).[8]
Myelodysplastic Syndrome
Allogenic stem cell transplant is considered being curative in cases of disease progression and is only indicated in intermediate- or high-risk patients with MDS.
Chronic Myeloid Leukemia/Chronic Lymphocytic Leukemia
Recipients with these two diseases come at the bottom of the list of patients who received allogeneic stem cell transplant in 2016. Hematopoietic stem cell transplantation has shown high cure rates but with availabletreatments like tyrosine kinase inhibitors and high success rates with low adverse risk profile, HSCTis reserved for patients with the refractory disease to first-line agents in CML.
Myelofibrosis, Essential Thrombocytosis, and Polycythemia Vera
Allogenic stem cell transplant has shown to improve outcomes in patients with myelofibrosis and those who had a diagnosis of myelofibrosis that was preceded by essential thrombocytosis and polycythemia vera.[9]
Solid Tumors
Autologous stem cell transplant is consideredthestandard of care in patients with germ cell tumor (testicular tumors) that are refractory to chemotherapy (after the third recurrence with chemotherapy).[10]HSCT has also been studied in medulloblastoma, metastatic breast cancer, and other solid tumors.
Non-Malignant Diseases
Aplastic Anemia
Systematic and retrospective studies have suggested an improved outcome with hematopoietic stem cell transplant in acquired aplastic anemia when compared with conventional immunosuppressive therapy.[11]Allogenic stem cell transplant has shown better outcomes when it was collected from bone marrow compared to peripheral blood in a study that involved 1886 patients with acquired aplastic anemia.[12]Patients with aplastic anemia need preparative regimen given they still can develop immune rejection to the graft.
Severe Combined Immune Deficiency Syndrome (SCID)
Large retrospective studies have shown increased overall survival in infants with SCID when they received the transplant early at birth before the onset of infections.[13]
Thalassemia
Allogenic stems transplant from a matched sibling donor is considered an option to treat Thalassemia and has shown 15-year survival reaching 80%. However, recent retrospective data showed similar overall survival compared with conventional treatment that consists of multiple transfusions in the case of thalassemia.[14]
Sickle Cell Anemia
Allogenic stem cell transplant is recommended for the treatment of sickle cell disease.[15]
Other Nonmalignant Diseases
Stem cell transplant has been used in the treatment of chronic granulomatous disease, leukocyte adhesion deficiency, Chediak-Higashi syndrome, Kostman syndrome, Fanconi anemia, Blackfan-Diamond anemia, and enzymatic disorders. Moreover, the role of stem cell transplant is being explored in autoimmune diseases including systemic sclerosis, systemic lupus erythematosus and has already shown promising results in cases like relapsing-remitting multiple sclerosis.[16]
There are no absolute contraindications for hematopoietic stem cell transplant.
Special equipment exists for the collection, preservation, and administration of stem cell products.
An interprofessional team approach is amainstay of ensuring the high-quality collection and infusion of stem cell products.
Preparation includes:
Mechanism of Action
The mechanism of action of stem cell transplant against malignancy in leukemia is based on the effect of the graft and donor immunity against malignant cells in recipients. These findings were demonstrated in a study that involved over 2000 patients with different leukemia. These patients received stem cell transplantation and showed that the lowest rate of relapses was in patients who received non-T-cell-depleted bone marrow cells and in those who developed GVHD compared to patients who received T-cell-depleted stem cells, those who did not develop GVHD, and patients who received syngeneic grafts. These findings support the notion that donor cellular immunity plays a central role in the engraftment's efficacy against tumor cells.[17]
The mechanism of action in autoimmune diseases is believed to be secondary to the increase in T-cell regulatory function which promotes immune tolerance. However, more studies are still needed to determine the exact pathophysiology.
In hemoglobinopathies, the transplanted stem cells produce functional cells after engraftment that replaces the diseased cells.
Administration
HLA Typing
HLA typing is an important step to determine the best donor suitable for stem cell collection. In theory, matched, related donors are the best candidates, followed by matched unrelated donors, cord blood, and then haploidentical donors. HLA typing is analyzed at either an intermediate-resolution level, which entails the detection of a small number of matched alleles between the donor serum and the recipient, or at a high-resolution level to determine the specific number of polymorphic alleles at a higher level. PCR and next-generation sequencing are used for HLA typing, and the results are reported as a score correlating with a match of two alleles for a specific HLA type. Different institutions use a different number of HLA subtypes for eligibility of donors but according to studies that showed matching for HLA-A, B, C, and DRB1 at a high-resolution level were associated with improved survival and outcomes.[18]Recommendations about donor HLA assessment and matching have been proposed by the Blood and Marrow Transplant Clinical Trials Network (BM CTN).[19]
The process may vary depending on the source of the stem cell site collection, whether it is bone marrow, peripheral blood, or cord blood. Moreover, there is a slight difference based on whether it is autologous, allogeneic, or syngeneic. For example, the procedure consists of initial mobilization of stem cells, in which peripheral blood stem cells are collected given the low number and the need for high levels of progeny cells, and then this is followed by preparative regimen and finally, infusion.
Mobilization and collection involved the use of medication to increase the number of stem cells in the peripheral blood given that there are not enough stem cells in the peripheral blood. The agents used include granulocyte colony-stimulating factors (G-CSF) or chemokine receptor 4 (CXCR4) blockers like plerixafor. G-CSF is believed to enhance neutrophils to release serine proteases which lead to a break of vascular adhesion molecules and the release of hematopoietic stem cells from the bone marrow. Plerixafor blocks the binding of stromal cell-derived factor-1-alpha (SDF-1) to (CXCR4) which leads to the mobilization of stem cells to the peripheral blood.[20]CD34+ is considered the marker for progenitor hematopoietic stem cells in the peripheral blood, and usually, a dose of 2 to 10 x 10/kg CD34+ cells/kg is needed for proper engraftment. Chemotherapy can be used in some instances for mobilization of hematopoietic stem cells; this process is termed chemoembolization.
The usual site of bone marrow collection is the anterior or posterior iliac crest. The procedure can be performed under local or general anesthesia. Complications include pain, fever, and serious iatrogenic complications can occur in less than 1% of cases. Multiple aspirations are done with each aspirate containing 15 mL. The goal is to collect up to 1 to 1.5 L of bone marrow product from the aspirations. The dose of nucleated cells from bone marrow should range between 2 to 4 x 10 cells/kg as studies showed that overall survival and long-term engraftment is strongly influenced by cell dose in allogeneic hematopoietic stem cell transplantation.[21]
The preparative regimen consists of administration of chemotherapy with or without total body irradiation for the eradication of malignant cells and induction of immune tolerance for the transfused cells to engraft properly. This process is not only limited to patients with malignancies but also extends to cases like aplastic anemia and hemoglobinopathies given that these patients have an intact immune system that could cause graft failure if there is no conditioning.
The preparative regimen is divided into myeloablative conditioning and reduced intensity conditioning. The preparative regimen depends on the disease being treated, existing comorbidities, and the source of the harvested hematopoietic stem cells. The preparative regimen consists of chemotherapy, total body irradiation, or both. There are different combination regimens used in the preparative period, and the choice of the regimen depends on the disease being treated, existing comorbidities, and previous exposure to radiation.
In the special case of SCID, there is no need for preparative regimen in patients receiving from HLA-matched siblings given that there are no abnormal cells that are needed to be eliminated and because immunosuppression caused by SCID can prevent graft rejection. Reduced-intensity conditioning is preferred in patients with prior radiotherapy, older age, the presence of comorbidities, and history extensive chemotherapy before BMT.[22]The advantages of using reduced-intensity conditioning include less need for transfusion due to the transient post-transplant pancytopenia and less damage to the liver in cases of chemotherapy and lung due to radiation.[23]However, the relapse rates are higher, but these regimens are more tolerated with a better safety profile in a specific patient population. Most of the chemotherapies used in preparative regimens consist of either potent immunosuppressive agents (high doses of cyclophosphamide 60 mg/kg IV), alkylating agents especially busulfan 130 mg/m2 IV, nucleoside analogs (fludrabine 40 mg/m2) and other agents like melphalan, antithymocyte globulin, rituximab, gemcitabine, and many others. Totalbodyirradiation (TBI) is performed using fractionated doses because it has shown less pulmonary toxicity when compared with one dose regimen.[24]The administration of the preparative regimen should immediately precede the bone marrow transplantation, and as a general rule, the effect of the regimen should produce bone marrow suppression within 1 to 3 weeks of administration.
Reinfusion of either fresh or cryopreserved stem cells can occur in an ambulatory setting and takes up to 2 hours. Before the infusion begins, quality measures are performed to ensure the number of CD34+ cells is sufficient.
Advantages and Disadvantages of Different Hematopoietic Stem Cells
The advantages of peripheral blood stem cells transplant (PBSCTs) include more rapid engraftment rate compared to bone marrow where it takes about 2 weeks of recovery in the former and is delayed for 5 days more in the latter,[25]but the use of post-transplant immunosuppressive regimen to prevent GVHD can prolong the increase in bone marrow products. Moreover, the rate of acute GVHD appears to be similar when compared with bone marrow transplantation in HLA- identical matched related donors.[25]However, chronic GVHD appears to be encountered more after peripheral blood stem cell transplant which could lead to more complications.[26]In the study by Anasetti et al., the primary endpoint was the difference in the 2-year overall survival seemed to be non-significant in the two groups. However, secondary end points showed more stable grafts with decreased graft failure in the group which received peripheral blood stem cell transplant but also this group had a higher incidence of chronic GVHD.[26]Other similar studies comparing both bone marrow transplant and peripheral blood SCTs concluded that the psychological burden due to chronic GVHD and the 5-year ability to restore normal activities including going back to work were better in the bone marrow transplanted group.[27]
The advantages of cord blood transplant include the rapid collection and administration which serves in treating urgent conditions, less frequency of infections, lower rates of GVHD with the same rate of GVT, less need for a stringent identical HLA. The disadvantages include delayed engraftment with a higher possibility of graft rejection and higher rates of disease relapses. The cord blood transplant is most used in patients without matched related or unrelated donors. A major study by Locatelli et al. demonstrated the utility of cord blood transplant in patients with thalassemia major and sickle cell anemia and showed similar 6-year overall survival in the CBT and BMT groups.[28]The most important factors that affect the outcome of CBT are the total nucleated cell dose and HLA matching with a recommended minimum dose of total nucleated cells of 2 x 10*7 cells/kg for successful engraftment. Theoretically, strict HLA matching is not required in the case of cord blood transplant given it is devoid of mature T cells but studies have shown better outcomes when matching recipients at HLA-A, HLA-B, HLA-C, and HLA-DRB1.[29]Given that a single blood cord unit might not contain the required amount of nucleated cells an approach using double cord transplant is used to overcome this problem. However, only one cord blood transplant product will predominate within 3 months of infusion. Further, randomized controlled trials failed to show a significant difference in terms of outcome benefits or risks between double cord blood and a single cord blood transplant.[30][31]
Haploidentical stem cell transplantation refers to the administration of bone marrow products from a first degree related haplotype-mismatched donor.[32]This helps in non-white patients like African American, Hispanics, and patients from countries where there is no wide access to resources as they have fewer chances of having a matched unrelated donor.[33]The advantages include lower cost and rapid availability of the hematopoietic cell products. However, the disadvantages include hyperacute GVHD which increases mortality and graft rejection.[34]This has been overcome by depletion of T cells responsible for the reaction mentioned above, but this also leads to delayed immune recovery and decreased graft versus tumor effect. Recently strategies including selective depletion of subsets of T cells including alpha-beta have shown improved outcomes when compared to conventional ex vivo depletion of large T-cell populations.[35]
Complications after bone marrow transplant can be divided into acute and chronic. Many factors can affect the occurrence of these adverse events including the age of the patient, baseline performance status, the source of stem cell transplant the type and intensity of the preparative regimen. Acute complications can occur in the first 90 days and include myelosuppression with neutropenia, anemia, thrombocytopenia, sinusoidal obstruction syndrome (SOS), mucositis, acute graft versus host disease, gram-positive/gram-negative infections, HSV, CMV, Candida, and Aspergillus. Chronic complications include chronic GVHD, infection with encapsulated bacteria and VZV. Levofloxacin is usually given by mouth or intravenously (IV) at day 1 post-transplant and is continued until absolute neutrophil count (ANC) is more than 1000 cells/uL or until the discontinuation of prednisonein cases of GVHD.[36]PCP prophylaxis is warranted given the immunosuppression following hematopoietic stem cell transplant.[37]Trimethoprim-sulfamethoxazole(TMP-SMX) is usually used, and several dosing regimens have been proposed. TMP-SMXis given 2 days per week until the patient is off immunosuppression.[38]Antifungal infection prophylaxis with fluconazole is recommended for 1 month following transplant as it has shown to decrease the incidence of fungal infections and no difference was seen when fluconazole was compared to voriconazole.[39][40]However, voriconazole is used in patients with a high-risk profile of developing severe forms of antifungal infection. Prevention against HSV and VZV is achieved with acyclovir that is continued for 1 month for the prevention against HSV and for 1 year for preventions against VZV.[41]Prophylaxis against CMV is only recommended in patients who test positive for CMV by PCR, and the treatment of choice is ganciclovir.
One unique syndrome encountered with cord stem cell transplant is cord colitis which involves diarrhea in recipients of cord blood and is believed to be secondary to Bradyrhizobium enterica[42]which usually responds to a course of metronidazole or levofloxacin.
Sinusoidal Obstruction Syndrome (SOS)
Also known as veno occlusive disease (VOD) is the result of chemotherapy during preparative regimen and occurs within 6 weeks of hematopoietic stem cell transplant. This syndrome consists of tender hepatomegaly, jaundice due to hyperbilirubinemia, ascites, and weight gain due to fluid retention. The incidence is reported to be 13.6% in an analysis study assessing the existing literature on the incidence of the disease.[43]The pathophysiology consists of endothelial damage to the hepatic sinusoids leading to obstruction and necrosis of the centrilobular liver.[44]The destruction of the sinusoids leads to hepatic failure and hepatorenal syndrome which areresponsible for the related mortality. The agents most commonly implicated in causing this syndrome are oral busulfan and cyclophosphamide. The use of IV busulfan has shown to decrease the occurrence of SOS.[45]The diagnosis is clinical and is based on hyperbilirubinemia greater than 2 mg/dL with the other clinical findings of tender hepatomegaly and fluid retention. Treatment consists of ursodeoxycholic acid (UDCA) which has shown to significantly decrease the occurrence of SOS when given pre and post-transplant.[46]Another medication, defibrotide, has shown efficacy in the treatment of SOS when it occurs.[47][48]
Idiopathic Pneumonia Syndrome (IPS)
This usually happens in the first 90 days post-transplant. The incidence is low and is related to direct chemotoxicity due to preparative regimen. Treatment with steroids is usually used although no randomized controlled clinical trials have been done to support their efficacy. Recently, etanercept has been studied in a randomized control trial in patients who develop this syndrome. The study assessed the addition of soluble TNF inhibitors to steroids in the treatment and has not shown added efficacy with combination therapy.[49]
Graft Rejection
The process of which there is a loss of bone marrow function after reconstitution following infusion of hematopoietic stem cells or if there is no gain of function after infusion and is termed graft failure or rejection. The incidence of failure is highest when there is a high HLA disparity that usually occurs in the case of cord blood and haploidentical donors and is lowest with autologous and matched donor siblings. Factors responsible for graft failure include but are not limited to functional residual host immune response to the donor cells, a low number of infused cells, in vitro damage during collection and cryopreservation, inadequate preparative regimen and infections.
Chimerism refers to the presence ofa cell population from a person in the blood of a different person. Checking for chimerism is an important step in ensuring engraftment and success of the transplantation. The physician does this by checking the expression of CD33 which indicates the presence ofgranulocytes and CD3 which indicate the presence ofT cells and confirming that most of the present cells are from the donor. The importance of effective chimerism has beendemonstrated in many studies that showed decreased relapse rates and increased survival in allogeneic transplantation.[50]
Graft Versus Host Disease
The graft versus host disease (GVHD) consists of the reaction between T-cells from the donor in allogeneic transplant and recipients HLA polymorphic epitopes that leads to a constellation of symptoms and manifestations. GVHD canbe categorized into acute and chronic which are both sub-categorized into classic and late onset, classic, and chronic overlap respectively.[51]Acute GVHD usually develops within three months. However, it can develop after 3 months and is termed delayed acute GVHD. Prophylaxis is usually achieved with calcineurin inhibitors, methotrexate, and anti-thymocyte globulins. Severity is estimated based on Glucksberg scale which classifies acute GVHD from grade I to VI, and treatment with either high dose prednisone or methylprednisolone isindicated in higher grades.[52]
Chronic GVHD occurs after three months and is represented by the involvement of multiple organs in a similar fashion to collagen vascular diseases. Grading has been developed by NIH (Global Grading System) to assess the severity of GVHD which determines the treatment modality and predicts survival [53]. Treatment is similar to that of acute GVHD, but the duration is usually over 2two years.[54]
Toxicity
Chemotherapy and radiation of preparative regimen along with post-transplant immunosuppression can induce severe pancytopenia in the first week following infusion of hematopoietic stem cells which can lead to life-threatening infection.This depends on the type and the dose of chemotherapy administered and factors related to the recipients. Chemotherapy causes a destruction of healthy,normal bone marrow products including neutrophils, macrophages, monocytes, and lymphocytes. Also, mucositis toxicity due to chemotherapy disrupts the barriers protecting against infectious agents, and use of indwelling intravenous catheters provides another mean of the entrance of infectious agents. Vaccination is recommended for the following agents according to the guidelines: pneumococcal conjugate (PCV), TDaP, Haemophilus influenzae, meningococcal conjugate, onactivated polio, recombinant hepatitis B, inactivated influenza, and MMR.[36]Several regimens of prophylaxis have been proposed to prevent infections depending on the risk stratification of patients (low-risk, high-risk, treatment of ongoing GVHD.
Many risk scoring tools exist for the evaluation of recipients of hematopoietic stem cell transplant and stratification of risks so that proper preparation and treatment can be established tominimize the risks and toxicities before, during, and after transplantation. Some of the most commonly utilized scores in clinical practice are the European Group for Blood and Marrow Transplantation (EBMT) risk score,[55]hematopoietic cell transplantation-comorbidity index/age,[56]and Armand disease risk index (DRI).[57]
Hematopoietic stem cell transplant use in clinical practice has been expanding in the last decade, and many clinical trials are still ongoing to assess its efficacyin different medical conditions.
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Hematopoietic Stem Cell Transplantation - StatPearls ...
The standard of care for fit multiple myeloma patients is to receive high-dose chemotherapy (HDT) with autologous stem cell rescue otherwise known as autologous stem cell transplant (ASCT) after completion of induction therapy. Autologous stem cell transplant can provide significant remission that is both long and deep, extending survival.
"Autologous" refers to the blood-making stem cells that are harvested from the patient to be a source of new blood cells after high-dose chemotherapy with melphalan. "Allogeneic" transplant, in which donor stem cells are used instead of the patient's own cells, is not performed in myeloma outside the context of a clinical trial.
High-dose therapy with stem cell rescue is a treatment option for many multiple myelomapatients, but several factors must be taken into consideration.
Age is the first factor to consider. Transplant is usually recommended for patients under age 65. Since high-dose chemotherapy is an intensive regimen, the patient must be medically fit enough to withstand it, with no major underlying medical issues. Some older patients are in excellent physical health and can be considered fit and transplant-eligible. Transplant eligibility is evaluated on an individual basis.
These risk-related factors include the type andthe stage of the disease, its aggressiveness and responsiveness to treatment, the levels of serum albumin and beta-2 microglobulin, and the presence or absence of certain chromosomal abnormalities in the patients myeloma cells. While there are similarities between patients, each patients disease has its own distinct characteristics. Therefore, general statements regarding patient outcomes both during the transplant procedure and post-transplant are inappropriate.
There is no conclusiveclinical data to suggest that transplantation earlier in the treatment regimen is better than waiting until later. Clinical trial results suggest that frontline therapy that includes an immunomodulatory drug and a proteasome inhibitor in combination may result in response rates and duration of response comparable to those of stem cell transplant, allowing some patients to postpone transplant until later in the course of the disease. This hypothesis is undergoing continued investigation.
Its important to remember that even if someone is a good transplant candidate, it is ultimately the patients decision whether or not to have a transplant. It is possible to have stem cells harvested and saved for a later treatment if the hospital has the storage capacity and the patient's insurance company will agree to pay for harvesting for later use leaving the patient open to other more immediate treatment options. Discuss these options with your physician and insurer.
Blood cell-making (hematopoietic) stem cells are located in the bone marrow*. Stem cell growth factors (also known as colony-stimulating factors) are injected to trigger the release of bone marrow stem cells into the bloodstream. These peripheral blood stem cells are then harvested and frozen for use within days, weeks, or years in the future. There are three main methods for stimulating the growth of blood cell-producing stem cells before they are harvested:
1. giving growth factors alone2. giving growth factors with chemotherapy3. using a stem cell mobilization agent with growth factors.
*You may also hear stem cell transplant referred to as hematopoietic stem cell transplant.
The medical term for removal of hematopoietic stem cells from the circulating blood (harvesting stem cells) is apheresis, a procedure whereby blood from the patient passes through a machine that separates and then removes stem cells. The rest of the blood is immediately returned to the patient. The procedure lasts 3 to 4 hours each day for 1 to 5 days, and is usually done on an outpatient basis.
Side effects of apheresis are temporary and are caused by changes in the volume of the patients blood as it circulates in and out of the apheresis machine, as well as by the blood thinners added to keep the blood from clotting during the procedure. The most common side effects experienced during apheresis are slight dizziness and tingling sensations in the hands and feet. Less common side effects include chills, tremors, and muscle cramps.
After collection, the peripheral blood is taken to the processing laboratory for freezing (cryopreservation). The stem cells are mixed with a solution containing dimethyl sulfoxide (DMSO), then frozen and stored in liquid nitrogen. The stem cells can be stored frozen for as long as necessary until the time they are transplanted. Excellent function of stems cells is retained for at least 10 years.
A number of studies have been completed to determine the number of stem cells you need to safely undergo high-dose therapy. The number is quantified by a laboratory technique called CD34+ cell analysis by flow cytometry. A minimum number of stem cells to safely complete a transplant is 2 million CD34+ cells per kilogram of body weight. The stem cell collection process continues daily until the planned number of stem cells is collected. Most transplant physicians collect enough stem cells for two transplants (at least 4 million CD34+ cells per kilogram of body weight).
After the harvested stem cells are frozen, the patient is ready to receive high-dose chemotherapy to destroy the myeloma cells. High-dose chemotherapy kills these cells inside the patients body more effectively than standard-dose chemotherapy.
Since high-dose treatment destroys the normal bone marrow in addition to the myeloma cells, the collected stem cells are unfrozen andgiven back into the bloodstream through an intravenous (into a vein) catheter one to two days after administration of the high-dose chemotherapy. This infusion is often referred to as the transplant. It is not a surgical procedure and usually takes place in the patients room over the course of 1 to 4 hours. Infused stem cells travel through the bloodstream to the bone marrow, where they begin to produce new blood cells, a process called engraftment. It takes 10 to 14 days for the newly produced blood cells to enter the bloodstream in substantial numbers, and the patient may be given growth factors to speed up this process. The average time for the chemotherapy, transplant, and recovery is approximately 3 weeks. Not all transplant centers require that patients remain in the hospital after the infusion of stem cells.
In addition to obliterating the bone marrow, high-dose chemotherapy can cause other severe side effects, which may require a stay in the hospital fortreatment during this period. Some of the more common side effects include nausea, vomiting, diarrhea, mouth sores, skin rashes, hair loss, fever or chills, and infection. Medications are given to prevent or lessen some of the expected side effects, and patients are closely monitored during and after the administration of high-dose chemotherapy.
Until engraftment of the stem cells takes place, the bodys immune system is weakened by the effects of the high-dose chemotherapy, and patients are very susceptible to developing infections. Even a minor infection like the common cold can lead to serious problems. Therefore, special precautions are necessary during recovery. Patients may remain in the hospital until the white blood cell counts reach a level safe enough for the patient to be discharged. The following supportive care measures may be required:
Patients and their caregivers are given instructions for maintaining a safe environment at home to help prevent infection while the immune system continues to recover.
After the stem cells have been infused, many transplant centers use white blood cell growth factors (e.g., Neupogen, Neulasta, Leukine) to help stimulate the bone marrow to produce normal blood cells. These injections continue until the white blood cell count returns to normal. During this time, a blood transfusion(s)may be necessary. Once symptoms resolve and the risk of serious infections is reduced, transfusions will no longer be needed. Although patients may be well enough to leave the hospital, the recovery process will continue at home for 1 to 4 months, and patients usually cannot resume normal activities for up to 3 to 6 months, although this varies from individual to individual. Having a support network is very important during this time. Waiting for the transplanted stem cells to engraft, for blood counts to return to safe levels, and for side effects to disappear is often the most difficult time for both patients and their loved ones. It is important to take things one day at a time: one day a patient may feel much better, but the next day feel too weak to do much more than sleep.
High-dose chemotherapy with stem cell rescue can place physical, psychological, emotional, and financial stresses on patients and their families. Patients may experience feelings of anger, depression, and anxiety over an unknown future and a lack of control. We urge you to take advantage of support services offered through the hospital and other organizations, including myeloma support groups, or to seek a referral from your oncologist for psychological counseling or psychiatric consultation.
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Autologous Stem Cell Transplant for Multiple Myeloma
DUARTE, Calif.--(BUSINESS WIRE)--City of Hope doctors presented data on an investigational bispecific antibody for multiple myeloma and the CMVPepVax, a City of Hope-developed vaccine against the cytomegalovirus, at this years ASH Annual Meeting.
City of Hope continues to be a leader in innovative research on investigational immunotherapies for blood cancers and improving stem cell transplants, said Eileen Smith, M.D., City of Hopes Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. New research at this years ASH conference includes promising investigational immunotherapies for lymphoma, multiple myeloma, leukemia and other blood cancers and an update on a City of Hope-developed vaccine to prevent a virus that can cause serious complications in stem cell transplant recipients.
Here are highlights of City of Hope research presented at the ASH conference:
Investigational bispecific antibody for multiple myeloma is well-tolerated and effective
Bispecific antibodies are an emerging immunotherapy against blood cancers. City of Hopes Elizabeth Budde, M.D., Ph.D., presented at this years ASH conference on mosunetuzumab. The research demonstrated that mosunetuzumab is a safe and effective investigational bispecific antibody for follicular lymphoma.
Talquetamab is an investigational therapy that is also demonstrating encouraging results for the treatment of relapsed multiple myeloma, according to a study led by Amrita Krishnan, M.D., director of the Judy and Bernard Briskin Center for Multiple Myeloma Research at City of Hope and chief, Division of Multiple Myeloma.
Talquetamab targets the G protein-coupled receptor family C group 5 member (GPRC5D) that has a high expression on malignant plasma cells and is limited on normal human tissue. The first-in-class bispecific antibody directs T cells to kill multiple myeloma cells by binding to both GPRC5D and CD3 receptors.
Patients with relapsed or difficult to treat multiple myeloma in the Phase 1 study received recommended Phase 2 doses as an injection on a weekly or biweekly basis. By increasing the doses slowly, researchers hope that will help to minimize the severity of cytokine release syndrome.
Krishnan presented data on 55 patients. For the study, 30 patients who received the therapy weekly (and their results were evaluable, meaning they could be included in the study) and 23 people who received it on a biweekly schedule were included. The study is ongoing.
In the weekly cohort, the overall response rate was 70% and there was a very good partial response or better in 57% of patients.
The response numbers are very strong and whats also remarkable is that the responses were durable and deepened over time in both groups, Krishnan said.
Cytokine release syndrome occurred in 73% of the weekly dose cohort, but only one patient had a severe case and it was treatable. Other side effects included neutropenia and dysgeusia.
We are excited that our results demonstrated that talquetamab is well-tolerated and highly effective at the Phase 2 dose level and with tolerable side effects, Krishnan said.
Further studies of the therapy on its own or in combination with other treatments for multiple myeloma are underway.
City of Hope-developed vaccine to prevent cytomegalovirus shows safety, tolerability
Despite therapies to help prevent the cytomegalovirus (CMV), which can flare up in blood marrow/stem cell transplant recipients who are immunocompromised, CMV infections are one of the most common complications in these patients. Furthermore, the antiviral drugs used to prevent flare-ups are toxic, expensive and increase the risk of other opportunistic infections.
City of Hope has developed an anti-CMV vaccine, known as CMVPepVax. At this years ASH conference, the results of a Phase 2 trial using CMVPepVax were reported by Ryotaro Nakamura, M.D., City of Hopes Jan & Mace Siegel Professor in Hematology & Hematopoietic Cell Transplantation in the Division of Leukemia.
The double blinded, placebo-controlled, randomized Phase 2 trial enrolled stem cell transplant recipients from four transplant centers, including City of Hope. Nakamura reported on data from 32 patients in the vaccine arm and 29 patients in the placebo arm.
CMVPepVax was delivered via injections 28 days after transplant and 56 days after the procedure.
Trial results demonstrated that there was no difference in CMV reactivation in both arms.
CMVPepVax was well-tolerated in patients with no increase in adverse side effects. Transplant outcomes were also similar between the two groups when comparing one-year overall survival, relapse-free survival, nonrelapse mortality, relapse and acute graft-versus-host disease (GVHD).
Significantly higher levels of CMV-targeting T cells were measured in patients in the vaccine arm who did not have CMV in their bloodstream. In patients who had the CMVPepVax injections, robust expansion of functional T cells also occurred.
Our results confirm that CMVPepVax is safe to use and provides an immune response, Nakamura said. Although the vaccine did not reduce the presence of CMV in the bloodstream, there were favorable CD8 T cell responses, which are protective in principle, but maybe didn't recover fast enough to prevent CMV from reactivating.
Next steps include researching whether stem cell donors who receive the vaccine can transfer immunity to patients, as well as providing a booster to patients. This may lead to faster immune responses after transplant.
Using probiotics for stem cell transplant patients
City of Hope is a leader in bone marrow and stem cell transplantation it was one of the first cancer centers nationwide to perform a bone marrow transplant and has performed more than 17,000 bone marrow/stem cell transplants since 1976. Because of this leadership, City of Hope doctors and scientists are investigating how to make the transplant process better, as well as how to deal with complications that may arise from the procedure, such as GVHD.
Led by Karamjeet S. Sandhu, M.D., an assistant professor in City of Hope's Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation, a City of Hope study examined how adding the probiotic CBM 588 to transplant recipients diets might decrease inflammation in the gut and lower the risk of GVHD. The results were discussed in an oral presentation at the ASH conference.
Sandhu explained that the body hosts microbial communities, known as the microbiome. These microbes help the body in several metabolic processes, such as digesting food, strengthening the immune system, protecting against other bacteria and producing vitamins, including B vitamins.
Recent studies have shown the microbiome can play a role in cancer risk and how a persons body responds to cancer treatment. In people with blood cancers who receive a transplant, there is a direct link between the health of microbiome and survival.
Imbalance among these microbial species have also been associated with several transplant complications including GVHD, said Sandhu, M.D. He added that the imbalance also contributes to morbidity and mortality.
For the study, Sandhu and his team used Clostridium Butyricum Miyairi 588 (CBM588), a probiotic strain that has been used in Japan for several decades to manage diarrhea caused by antibiotics or infections. CBM588 is a butyrate-producing bacteria present in the spore form in soil and food. Administration of CBM588 has shown anti-inflammatory and immune modulating effects, as well as evidence of anti-cancer activity.
This was the first study of CBM588 among bone marrow/stem cell transplant recipients. Fifteen patients received the current standard of care therapies to prevent GVHD and 21 received CBM588 in addition to standard of care for GVHD.
Our study demonstrated that CMB588 is safe and feasible to use in this patient population without increasing mortality, Sandhu said. We even noted an improvement in gastrointestinal GVHD, but further studies are needed to prove the effect and mechanism of action among recipients of bone marrow/stem cell transplantation.
Joint study examines somatic mutations in CMML patients, impact on stem cell transplants
Chronic myelomonocytic leukemia (CMML) is a rare form of leukemia that primarily affects older adults. The only potential cure at this time is allogeneic hematopoietic cell transplantation, also known as a stem cell transplant.
Research has shown that somatic mutations genetic changes that are acquired during life and not inherited are an important factor in determining prognosis for CMML patients. However, limited data are available regarding their impact on outcomes after CMML patients receive transplant.
A joint study between City of Hope and Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed the relationship between somatic mutations in CMML and their impact on stem cell transplants.
Additionally, the study aimed to evaluate two separate scoring systems commonly used in nontransplant CMML patients, the CMML-specific prognostic scoring system (CPSS) and molecular CPSS (CPSS-Mol), which takes into account the somatic mutations, to find out if they can predict the results of a transplant.
Led by City of Hopes Matthew Mei, M.D., an associate professor in City of Hopes Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, the study included 313 patients across 78 different transplant centers, all of whom underwent a comprehensive mutation analysis of 131 genes performed at City of Hope under the supervision of Raju K. Pillai, M.D., director of Pathology Core Laboratories in Beckman Research Institute of City of Hope.
The study found that 93% of patients had at least one mutation identified, and the median number of mutations was three. The most frequently mutated genes were ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined) and SRSF2 (31%); TP53 was mutated in 3% of patients.
Both the CPSS and CPSS-Mol were predictive of overall survival after transplant; however, neither system was able to identify patients who were at an increased risk of relapse. Furthermore, the incorporation of somatic mutations did not appear to refine the prognosis.
Our study is the largest analysis of CMML patients who underwent a stem cell transplant with paired mutation analysis, Mei said. Overall, patients with CMML remain at high risk for relapse after transplant. Novel therapies aimed at decreasing relapse and making transplants safer, as well as improved methods of predicting outcomes of transplant in CMML, are still critically needed.
Additional research on chimeric antigen receptor (CAR) T therapy and stem cell transplantation presented at ASH
Tanya Siddiqi, M.D., director of City of Hope's Chronic Lymphocytic Leukemia Program, also presented a poster on the Transcend NHL 001 trial at the ASH conference, and Ibrahim Aldoss, M.D., associate professor, City of Hope's Division of Leukemia, presented a poster on the outcomes of allogeneic hematopoietic cell transplantation in adults with Ph-like acute lymphoblastic leukemia.
City of Hope is a leader in blood cancer research and treatment. The National Cancer Institute-designated comprehensive cancer center has performed more than 17,000 bone marrow/stem cell transplants and is a leader in chimeric antigen receptor (CAR) T therapy, with nearly 800 patients treated with immune effector cells, including CAR T therapy, and nearly 80 open or completed trials.
About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nations Best Hospitals in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope, a subsidiary launched in 2019, serves employers and their health care partners by providing access to NCI-designated cancer center expertise. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
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City of Hope presents leading-edge research on blood cancer therapies and its vaccine to reduce stem cell transplant complications at American Society...
For Immediate Release: December 15, 2021
Today, the U.S. Food and Drug Administration approved Orencia (abatacept) for the prophylaxis (prevention) of acute graft versus host disease (aGVHD), a condition that occurs when donor bone marrow or stem cells attack the graft recipient, in combination with certain immunosuppressants. Orencia may be used in adults and pediatric patients two years of age or older undergoing hematopoietic stem cell transplantation (commonly known as bone marrow transplantation or stem cell transplantation) from an unrelated donor.
This is the first FDA drug approval for aGVHD prevention and incorporates real world evidence (RWE) as one component of the determination of clinical effectiveness. RWE is clinical evidence regarding the usage and potential benefits, or risks, of a medical product derived from analysis of real world data i.e., data relating to patient health status and/or the delivery of health care routinely collected data from a variety of sources, including registry data. There are significant ongoing efforts at the FDA to incorporate use of high-quality RWE to support regulatory decision-making.
Acute graft versus host disease can affect different parts of the body and become a serious post-transplant complication, said Richard Pazdur, M.D., director of the FDAs Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDAs Center for Drug Evaluation and Research. By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.
Acute GVHD is a potentially fatal complication that can occur after stem cell transplantation when the donors immune cells (the graft) view the recipients body (the host) as foreign, and the donated cells attack the body. The chances of developing aGVHD increase when the donor and recipient are not related or are not a perfect match.
The safety and efficacy of Orencia in combination with immunosuppressant therapy in patients age six years and older who underwent stem cell transplantation from a matched or mismatched unrelated donor were evaluated in two separate studies.
One study, GVHD-1, was a double-blind, placebo-controlled trial of 186 patients who underwent stem cell transplantation from a matched unrelated donor and randomly received Orencia or a placebo in combination with the immunosuppressive drugs. The study measured severe (grade III-IV) aGVHD-free survival, overall survival and moderate-severe (grade II-IV) aGVHD-free survival six months after transplantation. While severe aGVHD-survival was not significantly improved in patients who received Orencia (87%) compared to patients who received a placebo (75%), patients who received Orencia saw a 97% overall survival rate compared to 84% for patients who received a placebo. For moderate-severe aGVHD-free survival, patients who received Orencia saw a 50% rate compared to 32% for patients who received a placebo.
Additional evidence of effectiveness was provided by GVHD-2, a registry-based clinical study conducted using real world data from the Center for International Blood and Marrow Transplant Research in patients who underwent stem cell transplantation from a mismatched unrelated donor. This study analyzed outcomes of 54 patients treated with Orencia for the prevention of aGVHD, in combination with standard immunosuppressive drugs, versus 162 patients treated with standard immunosuppressive drugs alone. The study measured overall survival six months after transplantation. Patients who received Orencia saw a 98% overall survival rate compared to 75% for patients who received standard immunosuppression alone.
The most common side effects of Orencia for prevention of aGVHD include anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleed, decreased levels of specific white blood cells called CD4 lymphocytes, increased levels of magnesium in the blood and acute kidney injury. Patients who receive Orencia should be monitored for Epstein-Barr virus reactivation in accordance with institutional practices and receive preventative medication for Epstein-Barr virus infection before starting treatment and for six months post-transplantation. Patients should also be monitored for CMV infection/reactivation for six months post-transplant.
Orencia received Breakthrough, Orphan Drug and Priority Review designations for this indication. Development of this product was partially supported by the FDAs Orphan Products Grants Program, which provides grants for clinical studies on safety and efficacy of products for use in rare diseases or conditions.
Orencia was originally approved by the FDA in 2005 for the treatment of adult rheumatoid arthritis. Orencia is also approved for the treatment of polyarticular juvenile idiopathic arthritis and adult psoriatic arthritis.
The FDA granted approval of Orencia to Bristol Myers Squibb.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada, Swissmedic and MOH (Israels Ministry of Health). The application reviews are ongoing at the other regulatory agencies.
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12/15/2021
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FDA Approves First Drug to Prevent Graft Versus Host Disease | FDA - FDA.gov
Jorge E. Cortes, MD, has been an investigative leader for nearly 30 years in the development of numerous leukemia treatments.
It would be difficult to look at data involving practice-changing agents for patients with leukemia and miss the name Jorge E. Cortes, MD. An investigative leader for nearly 30 years, Cortes has led the development of numerous leukemia treatments, including trials for the second-generation tyrosine kinase inhibitor (TKI) bosutinib (Bosulif), which is widely used for chronic myeloid leukemia (CML); omacetaxine mepesuccinate (Synribo), a drug approved for patients with CML when TKIs have stopped working; the third-generation TKI ponatinib (Iclusig), another CML treatment; and glasdegib (Daurismo), a smoothened inhibitor approved for the treatment of older patients with acute myeloid leukemia (AML) and complications like heart or kidney disease that preclude use of intensive induction chemotherapy.
Today, Cortes is leading something even larger than drug trials: the Georgia Cancer Center at Augusta University, which named him its director in 2019, following a 20-plus year career at The University of Texas MD Anderson Cancer Center in Houston. Working to make Georgia Cancer Center a world-class facility and continuing with as much research as possible keeps Cortes busy, but he has still found time to cochair the 26th Annual International Congress on Hematologic Malignancies hosted by Physicians Education Resource (PER), LLC.
The hybrid interactive conference will be held from Thursday, February 24, 2022, to Sunday, February 27, 2022, at the Eden Roc in Miami Beach, Florida. The 4-day event will focus on leukemias, lymphoma, and myeloma. Its presentations and panels will cover the latest developments in chimeric antigen receptor (CAR) T-cell therapy, the most pivotal new trial results, the use of genomics and molecular testing in hematological cancers, and how to cope with the emerging value basedcare landscape.
At MD Andersonwhere he rose from a fellow to the deputy chair of the Department of Leukemia Cortes established himself as one the worlds leading leukemia researchers and the coauthor of more than 1000 published papers. At Georgia Cancer Center, he has less time for research, but he has still managed to launch another multicenter trial of an experimental CML treatment.
[Cortes] is truly a world expert on all things leukemia, has peerless clinical experience, and is an undisputed leader in the field. He has been instrumental in a very large number of trials that have led to drug approvals, and he ranks among the most published authors in the scientific world, Alexander E. Perl, MD, MS, said. Perl is an associate professor of medicine at Perelman School of Medicine at the University of Pennsylvania and a member of the leukemia program in the Abramson Cancer Center in Philadelphia, who has worked with Cortes on trials of FLT3 inhibitors.
Hes an excellent speaker as well, Perl added, and will make a great chair for the conference.
Courtney D. DiNardo, MD, MSCE, a clinical researcher in the Department of Leukemia at MD Anderson Cancer Center, said the key to Cortes success is a level of drive that is unusual even in a world of highly driven people.
Hes always moving; hes always thinking. Hes kind of like the Energizer Bunny. He just keeps going and going, she said.
The agenda for the International Congress on Hematologic Malignancies features dozens of presentations and panels, and most of them are followed directly by question-and-answer sessions with thought leaders. The other program cochairs are Andre H. Goy, MD, physician in chief at Hackensack Meridian Health Oncology Care Transformation Service, chairman and chief physician officer at John Theurer Cancer Center, Lydia Pfund Chair for Lymphoma, Academic Chairman Oncology at Hackensack Meridian School of Medicine, and professor of medicine at Georgetown University in Hackensack, New Jersey, and Sagar Lonial, MD, FACP, chief officer of Winship Cancer Institute of Emory University in Atlanta, Georgia.
The key topics for discussion will include the following:
A MODERN LANDSCAPE
Cortes recently sat down for an in-depth interview with OncologyLive to preview the conference and share his thoughts about the major trends in leukemia treatment.
When I started, leukemia treatment was easy, Cortes said. [Individuals] with AML got 7 plus 3 [cytarabine continuously for 7 days and an anthracycline on each of the f irst 3 days of a treatment cycle]. Patients with CML would get interferon. And individuals with a model of proliferative neoplasms got hydroxyurea. And that was it. It was very easy. Unfortunately, the results were terrible.
Nowadays, theres a lot more complexity in our understanding of the biology. Theres not one AML, theres not one ALL [acute lymphoblastic leukemia]. There are a lot more challenges in classifying the cancer, and the same is true in treatment. We have a lot more treatment options, but the increase in treatment options means that its a lot harder to pick the right one. How do I select when I have 3 or 4 options? How do I combine them? What is the relative value? The answers to all these questions are evolving very rapidly because there [are] a lot of data coming out.
Among the biggest topics of conversation at the hematology conference will be recent trial results for CAR T-cell therapy. In October, the FDA approved brexucabtagene autoleucel (Tecartus) for adults with relapsed or refractory B-cell precursor ALL. The approval was based on results from the ZUMA-3 trial (NCT02614066), in which 71 patients were enrolled and underwent leukapheresis. The CAR T-cell therapy was then successfully manufactured for 65 of those patients and administered to 55. At the median follow-up of 16.4 months, 31 (56%) patients reached complete remission (CR). The median duration of remission was 12.8 months (95% CI, 8.7 months-not estimable [NE]). Median relapse-free survival was 11.6 months (95% CI, 2.7-15.5), and median overall survival (OS) was 18.2 months (95% CI, 15.9 months-NE). Among responders, median OS was not reached at the time of analysis.1
A few days before that approval, Kite submitted a supplemental biologics license application to the FDA to expand the current indication of the CAR T-cell therapy axicabtagene ciloleucel (Yescarta) to include the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma. The application was based on findings from the phase 3 ZUMA-7 trial (NCT03391466), which showed improved event-free survival compared with standard of care after a median follow-up of 2 years. Among the 359 patients who were randomized 1:1 to CAR T-cell therapy or standard of care, patients in the experimental group experienced a 60% reduction in events.2
We will present a lot of data on CAR T-cell therapy, Cortes said. This is a rapidly emerging field, with a large number of new trial results, not just in acute lymphoblastic leukemia but, increasingly, in other areas as well, and we dedicate a whole section of the conference to the understanding of CAR T-cells. This is something that was addressed last year, but we will do it again because new information keeps coming, and now theres the new indication in acute lymphoblastic leukemia.
Cortes said that studies with venetoclax (Venclexta) in AML will also be discussed. We will present [findings] from the initial phase 1 and phase 2 trials and then the randomized phase 3 studies that cemented venetoclax as the standard of care in a short period of time.
Results of the phase 3 Viale-A (NCT02993523) trial led to venetoclax being adopted as the standard treatment in older patients with previously untreated AML. The trial randomized 286 patients to receive azacitidine plus venetoclax and 145 patients to receive azacitidine plus placebo. At a median follow-up of 20.5 months, the median OS was 14.7 months in the azacitidine/venetoclax group vs 9.6 months in the control group (HR for death, 0.66; 95% CI, 0.52-0.85; P < .001). Participants were also more likely to experience CR (36.7% vs. 17.9%; P < .001) and composite CR (66.4% vs 28.3%; P < .001). Serious adverse events occurred in 83% of patients in the experimental arm vs 73% of patients in the control arm.3 These data, as well as data from the phase 3 VIALE-C trial (NCT03069352), supported the FDA decision in October 2020 to grant regular approval to venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine for the treatment of adults 75 years and older with newly diagnosed AML.4,5
Another major focus of conversation will be research indicating that many patients with CML who have responded completely to TKI treatment and gone several years with no evidence of disease can safely discontinue treatment.
We have [an] increasing amount of trial data on this issue, Cortes said. We want to present the data from The LAST Study [NCT02269267] and elsewhere and put those trials in context and explore which patients are good candidates for treatment discontinuation and how we can do it right to minimize the risk for patients.
EXPANDING HORIZONS
Cortes credits his career in medicine to his uncle. When I was in high school, I wanted to be a dentist for some reason, but my uncle, whom I was very close with, asked me why I wanted to limit myself to treating the mouth when I was a good enough student to become a doctor and treat the whole body. Eventually he convinced me that medicine was probably a better path for me, he said.
The decision to specialize in leukemia treatment and research also happened more by chance than by design. Cortes attended medical school and did his residency in his native Mexico before arriving in Houston for a hematology fellowship at The University of Texas Health Science Center. A portion of his rotation was held across the street at MD Anderson Cancer Center, where he met the team working on leukemia. Impressed by the investigators in the laboratory and the work they were doing, Cortes switched his program to focus on leukemia. More than 1000 papers later, his focus remains unchanged.
Remember, were talking about almost 30 years ago, so in those days, [treating leukemia] was very, very challenging, Cortes said. There were very few new therapies available in leukemia, but there was a good opportunity to study because access to tissue is readily available. You also got the outcomes very quickly, so the clinical trials could be conducted rapidly.
Location was also important to fueling his research. [Houston] was a very active environment for research, Cortes said. There were lots of clinical trials, lots of academic discussions and interaction, so I thought it was a field that was very ripe for discoveries, and sure enough, a lot of new things have happened since then. Some of them, Ive been a part of, and some of them, Ive been a witness to, but its been a very rapid development.
Cortes interest in and experience with TKIs dates all the way back to the beginning. He was investigating CML with Moshe Talpaz, MD; Hagop M. Kantarjian, MD, a 2014 Giants of Cancer Care award winner in the leukemia category; and others at MD Anderson when the initial phase 1 trials of imatinib (Gleevec) began. He saw the incredible efficacy of the drug in those first patients and realized the great potential of targeted medications, specifically with TKIs.
The potential has been recognized in recent years in the expansion of targeted agents and a growing number of assays. Strategies for selecting the best therapies will be a major topic of conversation at the International Congress on Hematologic Malignancies.
We will have an outstanding presentation on the increasing complexity and the molecular diversity of acute lymphoblastic leukemia, which is a rapidly evolving area. Its become very complex, but also very specific, so this presentation will discuss how to use that information to manage patients, Cortes said. We will have the same sort of presentation for acute myeloid leukemia because again, its become a necessity to assess your patient to understand how to proceed with treatment.
There will also be information on these molecular abnormalities in individuals that do not have leukemia but do [have] predisposing factors, these CHIPsor clonal hematopoiesis of indeterminate potential. We have analyses of what these clonal entities mean, and we need to continue discussing them as we try to understand how they should affect our approach.
SHAPING THE NEXT GENERATION
You could say that Cortes enjoys being in the weeds of drug development, having a hand in the process from start to finish. He enjoys the complexity of running large drug trials, analyzing early-stage data to construct late-stage protocols, assembling research teams, and working with both drug companies and the FDA.
Drug development is a very complex endeavor, he said. Having a drug that works is obviously very important, but you have to design the trials in such a way that you get not only the academic answers and the clinical answers that you want, but also the data you need for regulatory approval. You also need to work with a lot of different groups investigators, sponsors, regulatory authorities, and most importantly, you have to work with patients. You need to recruit and enroll them.
Cortes noted that one of the key challenges is adapting opinions about drugs as new information becomes available and modifying trial design accordingly.
Even when the drugs look good initially, you also have to acknowledge that you know very little, and sometimes you learn things that that you didnt expect, he said, citing his experience with the agent ponatinib. It looked like a wonderful, very effective drug, but we learned that ponatinib had risk of arterial occlusive eventsheart attacks, strokes, and things like thatwhich was completely unexpected. The [challenge] was how to react to that. How do you balance the risk-benef it ratio? How do you [work] with the sponsor, the regulator agencies, and the patients?
Cortes strategy for managing these adverse effects secured ponatinib its 2012 FDA approvalalbeit with a black box warningfor the treatment of adults with CML and Philadelphia chromosomepositive ALL. Last year, the FDA expanded the indication. Both approvals were supported by data from the phase 2 PACE trial (NCT01207440)6; the second indication was also supported by data from the phase 2 OPTIC trial (NCT02467270).7
When we talk about what it takes to run a good trial, it all sounds straightforward, almost to the point of being obvious, but its not, DiNardo said. Doing good clinical research is a challenge, and some people are much better at it than others. I worked with Dr Cortes on several trials when I was new to the leukemia team at MD Anderson, and I am very happy I got a chance to learn from the best.
LOOKING BEYOND THE CURVE
Among the discussion of new trial results and new diagnostic tests, the International Congress on Hematologic Malignancies will also explore a relatively new concern: weighing the relative value of various potential treatments beyond their statistical significance.
Youre looking to maximize value for the patient, Cortes said. In a randomized trial, you [are looking to] get an improvement in survival that has a statistical value. But statistical significance may or may not mean something clinically. If [the survival benefit] is just a few weeks and the toxicity profile is harsh, how much of that extra time is spent in the hospital or suffering because of adverse effects? The survival benefit can be somewhat diluted by what kind of lifestyle you have. Youre alive, but are you living a normal life or at least close-to-normal life? And then, you know, how much are you paying for each week or month of extended survival? These are all things you need to consider, and were seeing more interest in thinking about how to balance them.
Cortes has taken a particular interest in improving quality of life for older patients and those with comorbidity that made traditional treatments hard to tolerate. Age alone doesnt make you less able to tolerate treatment, but it is more common that older patients will not be able to tolerate treatment, he said.
Cortes interest in investigating treatments for older patients helped inspire his work to develop glasdegib. The agent was approved in November 2018 in combination with low-dose cytarabine for patients with newly diagnosed AML who are 75 years or older with comorbidities that preclude intensive induction chemotherapy.8 That approval was supported by data from the BRIGHT AML 1003 trial (NCT01546038), in which 115 patients were randomized to receive low-dose cytarabine with or without glasdegib. After a median follow-up of 20 months, median OS was 8.3 months (95% CI, 4.4-12.2) in the investigative arm vs 4.3 months (95% CI, 1.9-5.7) in the control arm (HR, 0.46; 95% CI, 0.300.71; P = .0002).
[Older patients] have more comorbidities; they frequently take other medications, so you have to consider drug-drug interactions, Cortes said. There is also a tendency to give uppatients give up on themselves, doctors are more likely to give up on [finding treatments]and you need to avoid that. Life expectancy is much longer now than it was 30 years ago. For trial [design] purposes, we used to consider patients over 55 [years] as elderly. We wouldnt even [enroll them to] stem cell trials. Nowadays that sounds ridiculous. We realize that its just as important to combat cancer in these patients as it is in patients of any other age.
CARVING OUT A CORNER OF CARE
To relax and recharge, Cortes naturally enjoys something that keeps him moving full speed ahead: long-distance running. I love to run. I have done 8 marathons so far. Ive run them in Chicago, Boston, New York, and Houston. Ill be doing Houston again [in 2022], and hopefully that will qualify me to return to Boston, said Cortes, whose best marathon time is 3 hours and 30 minutes.
Why running? Part of the allure is the chance to get away from stuffy indoor spaces and spend long periods outside. He even enjoys bad-weather days because he likes making himself endure conditions that would send others to the treadmill.
The challenge is the point of long-distance running. Its demanding. The race is demanding. The training is demanding. But it gives you a feeling of accomplishment, he said. I also like that its an individual sport. If I have a bad day, Im not hurting any teammates. Running lets you run your race, at your own pace. You set your goals, and its fun to meet them. But if you dont, you just try again.
References
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Adaptation Is Key to Advancing Care for Adult Patients With Leukemia - OncLive
Ongoing Phase 2 clinical trial for MAU868 in kidney transplant patients; potential first-in-class
MAU868 Phase 2 data for kidney transplant to readout mid-2022
BK Virus is a leading cause of transplant loss and transplant-associated morbidity
BRISBANE, Calif., Dec. 17, 2021 (GLOBE NEWSWIRE) -- Vera Therapeutics, Inc. (Nasdaq: VERA), a clinical-stage biotechnology company focused on developing treatments for immunological diseases that improve patients lives, announced today that it has acquired MAU868, a first-in-class monoclonal antibody to treat BK Virus (BKV) infections, and has entered into a credit facility with Oxford Finance LLC (Oxford) to provide borrowing capacity up to $50 million. MAU868, acquired from Amplyx Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., has the potential to neutralize infection by blocking BKV virions from binding to host cells.
BKV is a leading cause of kidney transplant loss and transplant-associated morbidity, and there are currently no available antiviral treatments in the U.S. We are excited to acquire MAU868 from Pfizer and carry it forward in development, said Vera founder and CEO Marshall Fordyce, MD. The acquisition of MAU868, a potentially transformative treatment for BKV, is consistent with our strategy to diversify our pipeline with new molecules that leverage our strengths and serve adjacent populations. We believe, based on currently available data, that MAU868 has the potential to significantly impact outcomes for kidney transplant patients and become the first effective therapy for BKV. We look forward to working with regulators to establish a new standard of care for kidney transplant patients.
MAU868 is currently undergoing a randomized, double-blind, placebo-controlled Phase 2 clinical trial to assess the safety, pharmacokinetics, and efficacy for the treatment of BKV in kidney transplant patients. MAU868 has been shown in an interim analysis of week 12 data from Cohort 1 and 2 of a Phase 2 study to be well tolerated and showed a greater proportion of subjects with decrease in BK plasma viral load versus placebo. Full Cohort 1 and 2 interim analysis results will be submitted for presentation at a conference in mid-2022.
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Up to 90 percent of healthy adults are infected with BKV, but it remains latent in kidney and bladder tissues. Reactivation occurs in the setting of immune suppression, and causes clinical disease in the transplant setting. BKV is a significant cause of complications in these immunocompromised patients, including in kidney transplant and hematopoietic stem cell transplant (HSCT) recipients. In kidney transplant recipients, BKV is a leading cause of allograft loss and poor outcomes, while in HSCT recipients, the virus significantly increases the risk of severe hemorrhagic cystitis, which causes bladder damage. There are currently no approved treatments for BKV in the U.S.
MAU868 Asset Acquisition In partial consideration for the asset acquisition, Vera made an upfront payment of $5.0 million. In addition to the upfront payment, Vera is also obligated to make certain milestone payments in an aggregate amount of up to $7.0 million based on certain regulatory milestones. Further, Vera is required to pay Amplyx low single-digit percentage royalties based on net sales on a country-by-country and product-by-product basis. The rights to MAU868 that Vera acquired from Amplyx are subject to a license agreement by and between Amplyx and Novartis International Pharmaceutical AG, pursuant to which Vera is obligated to make certain milestone payments in an aggregate amount of up to $69.0 million based on certain clinical development, regulatory and sales milestones. Further, the Company is required to pay Novartis mid-to-high single-digit percentage royalties based on net sales on a country-by-country and product-by-product basis.
Credit Facility Vera also announced today that they entered into a credit facility with Oxford Finance. Under the terms of the loan agreement, Oxford will provide Vera with borrowing capacity of up to $50 million. The initial $5 million funded at closing, and an additional $45 million will be available in minimum draws of $5 million, at Veras option through the end of 2022. The debt facility provides for at least 48-months of interest-only at close. There are no warrants or financial covenants associated with the credit facility. Armentum Partners served as the Companys financial advisor on the debt financing.
About VeraVera Therapeutics is a clinical-stage biotechnology company focused on developing treatments for serious immunological diseases. Veras mission is to advance treatments that target the source of immunologic diseases in order to change the standard of care for patients. Veras lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgA nephropathy (IgAN), also known as Bergers disease. Vera is also developing MAU868, a monoclonal antibody that neutralizes infection with BK Virus, a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. For more information, please visit http://www.veratx.com.
Forward-looking Statements
Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential efficacy of our product candidates, research and clinical development plans, the scope, progress, and results of developing our product candidates, strategy, regulatory matters, including the timing and likelihood of success of obtaining drug approvals, market opportunity and our ability to complete certain milestones, the timing of the expected closing of the debt financing, and the expected use of the net proceeds therefrom. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as plans, will, anticipates, goal, potential, and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Veras current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the ability to realize the anticipated benefits of the acquisition, including the possibility that the expected benefits from the acquisition will not be realized or will not be realized within the expected time period, risks and uncertainties associated with Veras business in general, the impact of the COVID-19 pandemic, and the other risks described in Veras filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
ContactsInvestor Contact:IR@veratx.com
Media Contact:Greig Communications, Inc.Kathy Vincentkathy@greigcommunications.com
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Vera Therapeutics Announces Acquisition of Monoclonal Antibody From Pfizer to Treat BK Virus in Transplant Patients - Yahoo Finance