StemCell Therapy

Doctors are reporting unprecedented success from a new cell and gene therapy for multiple myeloma, a blood cancer that's on the rise. Although it's early and the study is small 35 people every patient responded and all but two were in some level of remission within two months.

In a second study of nearly two dozen patients, everyone above a certain dose responded.

Experts at an American Society of Clinical Oncology conference in Chicago, where the results were announced Monday, say it's a first for multiple myeloma and rare for any cancer treatment to have such success.

Chemotherapy helps 10 to 30 percent of patients; immune system drugs, 35 to 40 percent at best, and some gene-targeting drugs, 70 to 80 percent, "but you don't get to 100," said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.

"These are impressive results" but time will tell if they last, he said.

ABOUT THE DISEASE

Multiple myeloma affects plasma cells, which make antibodies to fight infection. More than 30,000 cases occur each year in the United States, and more than 115,000 worldwide. It's the second fastest growing cancer for men and the third for women, rising 2 to 3 percent per year, according to the National Cancer Institute. About 60,000 to 70,000 Americans have it now.

Nine new drugs have been approved for it since 2000 but they're not cures; only about half of U.S. patients live five years after diagnosis.

With cell therapy, "I can't say we may get a cure but at least we bring hope of that possibility," said Dr. Frank Fan. He is chief scientific officer of Nanjing Legend Biotech, a Chinese company that tested the treatment with doctors at Xi'an Jiaotong University.

HOW IT WORKS

The treatment, called CAR-T therapy , involves filtering a patient's blood to remove immune system soldiers called T cells. These are altered in a lab to contain a gene that targets cancer and then given back to the patient intravenously.

Doctors call it a "living drug" a one-time treatment to permanently alter cells that multiply in the body into an army to fight cancer. It's shown promise against some leukemias and lymphomas, but this is a new type being tried for multiple myeloma, in patients whose cancer worsened despite many other treatments.

THE STUDIES

In the Chinese study, 19 of 35 patients are long enough past treatment to judge whether they are in complete remission, and 14 are. The other five had at least a partial remission, with their cancer greatly diminished. Some are more than a year past treatment with no sign of disease.

Most patients had a group of side effects common with this treatment, including fever, low blood pressure and trouble breathing. Only two cases were severe and all were treatable and temporary, doctors said.

The second study was done in the U.S. by Bluebird Bio and Celgene, using a cell treatment developed by the National Cancer Institute. It tested four different dose levels of cells in a total of 21 patients. Eighteen are long enough from treatment to judge effectiveness, and all 15 who got an adequate amount of cells had a response. Four have reached full remission so far, and some are more than a year past treatment.

WHAT EXPERTS SAY

The results are "very remarkable" not just for how many responded but how well, said Dr. Kenneth Anderson of Dana-Farber Cancer Institute in Boston.

"We need to be looking for how long these cells persist" and keep the cancer under control, he said.

Dr. Carl June, a University of Pennsylvania researcher who received the conference's top science award for his early work on CAR-T therapy, said "it's very rare" to see everyone respond to a treatment. His lab also had this happen all 22 children testing a new version of CAR-T for leukemia responded, his colleagues reported at the conference.

"The first patients we treated in 2010 haven't relapsed," June said.

Dr. Michael Sabel of the University of Michigan called the treatment "revolutionary."

"This is really the epitome of personalized medicine," extending immune therapy to more types of patients, he said.

NEXT STEPS

Legend Biotech plans to continue the study in up to 100 people in China and plans a study in the U.S. early next year. The treatment is expected to cost $200,000 to $300,000, and "who's going to pay for that is a big issue," Fan said.

"The manufacturing process is very expensive and you can't scale up. It's individualized. You cannot make a batch" as is done with a drug, he said.

Nick Leschly, Bluebird's chief executive, said the next phase of his company's study will test what seems the ideal dose in 20 more people.

Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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A first: All respond to gene therapy in a blood cancer study - ABC News

In Brief Researchers have successfully used immunotherapy to "turn off" asthma and allergic responses in animals. This work will eventually be used to create one-shot treatments that permanently silence allergies. Erasing Asthma

Scientists from the University of Queensland have used gene therapy to turn off the immune response responsible for asthma. The team believes their technique may also be able to permanently silence severe allergy responses to common allergens such as bee venom, peanuts, and shellfish. Thus far, the research has been successful in animal trials, and if it can be replicated in human trials, it may provide a one-time treatment for asthma and allergy patients.

The technique erases the memory of the cells which cause allergic reactions using genetically modified stem cells that are resistant to allergens. We have now been able wipe the memory of these T-cells in animals with gene therapy, de-sensitizing the immune system so that it tolerates the [allergen] protein, lead researcher Ray Steptoe said in a press release. We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient. Those engineered cells produce new blood cells programmed to express the protein and target specific immune cells, which turn off the allergic response.

According to the Centers for Disease Control (CDC), about 1 in 12 people (25 million) in the U.S.have asthma, and these numbers are increasing annually. As of 2007, the last year for which the CDC has data, asthma cost the U.S. approximately $56 billion in costs for medical bills, lost work and school days, and early deaths. According to the World Health Organization (WHO), 235 million people worldwide have asthma, which is the most common chronic childhood disease, occurring in all countries regardless of level of development.

The researchers findings must now besubjected to further pre-clinical investigation, with the aim of replicating the results in the laboratory using human cells. The longer term goal will be a one-time gene therapy injection that would replace short-term allergy treatments, which vary in their effectiveness. We havent quite got it to the point where its as simple as getting a flu jab so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals, Dr. Steptoe said in the press release.

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A New Gene Therapy Could Hold the Key to Curing Allergies and Asthma - Futurism

A consultant studies a mammogram. The drug olaparib could slow cancer growth by three months, researchers have found. Photograph: Rui Vieira/PA

A type of inherited and incurable breast cancer that tends to affect younger women could be targeted by a new therapy, researchers have found.

A small study presented at the worlds largest cancer conference found treating patients with the drug olaparib could slow cancer growth by three months and be less toxic for patients with inherited BRCA-related breast cancer.

Researchers said there was not enough data to say whether patients survived longer as a result of the treatment.

We are in our infancy, said Dr Daniel Hayes, president of the American Society of Clinical Oncology and professor of breast cancer research at the University of Michigan. This is clearly an advance; this is clearly proof of concept these can work with breast cancer.

Does it look like its going to extend life? We dont know yet, he said.

The drug is part of the developing field of precision medicine, which targets patients genes to tailor treatment.

It is a perfect example of how understanding a patients genetics and the biology of their tumor can be used to target its weaknesses and personalize treatment, said Andrew Tutt, director of the Breast Cancer Now Research Centre at The Institute of Cancer Research.

Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation. The study was the first to show olaparib can slow growth of inherited BRCA-related breast cancer. The drug is not yet approved for that use.

People with inherited mutations in the BRCA gene make up about 3% of all breast cancer patients, and tend to be younger. The median age of women in the olaparib trial was 44 years old.

BRCA genes are part of a pathway to keep cells reproducing normally. An inherited defect can fail to stop abnormal growth, thus increasing the risk of cancer. The study examined the effectiveness of olaparib against a class of BRCA-related cancers called triple negative. Olaparib is part of a class of four drugs called PARP-inhibitors that work by shutting down a pathway cancer cells use to reproduce.

The study from Memorial Sloan Kettering Cancer Center in New York randomly treated 300 women with advanced, BRCA-mutated cancer with olaparib or chemotherapy. All the participants had already received two rounds of chemotherapy.

About 60% of patients who received olaparib saw tumors shrink, compared with 29% of patients who received chemotherapy. That meant patients who received olaparib saw cancer advance in seven months, versus four months for only chemotherapy.

Researchers cautioned it is unclear whether olaparib extended life for these patients, and that more research was needed to find out which subset of patients benefit most from olaparib.

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New therapy offers hope against incurable form of breast cancer - The Guardian

By Staff ReporterStaff Reporter , 06-Jun-20172017-06-06T00:00:00Z Last updated on 06-Jun-2017 at 10:36 GMT2017-06-06T10:36:21Z

Hitachi Group subsidiary PCT Cell Therapy Services will provide clinical manufacturing services for Orchards autologous gene therapy for the treatment of adenosine deaminase deficiency.

Under terms of the deal, PCT will make clinical supplies of OTL-101, an autologous ex-vivo gene therapy for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID).

The Manufacturing Services Agreement (MSA) is an extension of a previous contract between the UK-based Orchard Therapeutics and its contract development and manufacturing organisation (CDMO).

We are very pleased to extend our relationship with PCT into a full GMP manufacturing services agreement for OTL-101, Orchards chief manufacturing officer Stewart Craig said in a statement.

As a world-leading CDMO for cell-based therapeutic products, this is an important step in advancing our lead program for the treatment of children afflicted with ADA-SCID.

PCTs CEO Robert Preti added the expansion will now include clinical manufacturing in support of [Orchards] ADA-SCID gene therapy is testament to our successful collaboration and our dedicated stewardship of this important program.

The clinical results are cause for hope among this patient population and we look forward to helping advance this important new therapeutic towards commercialisation.

The deal comes after Orchard announced it had contracted Dutch CMO PharmaCell to manufacture products from its gene therapy pipeline earlier this year, and seven months after the firm inked an alliance with gene and cell therapy firm Oxford BioMedica for process development services and cGMP-grade manufacture of lentiviral vectors.

Orchard did not supply further information when contacted by this publication.

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Orchard Therapeutics hits up Hitachi CDMO to make autologous gene therapy - BioPharma-Reporter.com

Scientists have used gene therapy to 'switch off' the immune response that causes asthma, and are hopeful that the same technique could be used to target other severe allergies to peanuts, bee venom, and shellfish,keeping them at bay for life.

The research, which has so far seen success in animal trials, works byerasing the memory of the cells responsible for causing an allergic reaction, and if replicated in humans, could offer a one-off treatment for allergy patients.

"The challenge in asthma and allergies is that these immune cells, known as T-cells, develop a form of immune 'memory', and become very resistant to treatments,"says lead researcherRay Steptoefrom the University of Queensland (UQ) in Australia.

"We have now been able 'wipe' the memory of these T-cells in animals with gene therapy, de-sensitising the immune system so that it tolerates the [allergen] protein."

An allergic response is a hypersensitive immune reaction to a substance that is normally harmless. When people are exposed to their allergic trigger, it can cause anything from itchy eyes and a runny nose to - in the most extreme cases -death.

Asthma is a common allergic response of the airways affecting 2.5 million Australiansand hundreds of millions around the world. About 80 percent of people who experience asthma in Australia are susceptible to hay fever - an allergic response to rye grass pollen.

"When someone has an allergy or asthma flare-up, the symptoms they experience results from immune cells reacting to protein in the allergen," says lead researcherRay Steptoefrom the University of Queensland (UQ) in Australia.

While previous research has looked into using nanoparticle 'trojan horses' to smuggle the allergen past the immune system, and at new immunotherapy approaches, right now, the most effective treatment for people suffering from allergies is to simply avoid all known triggers.

To figure out a better way, Steptoe and his teamtook bone marrow from mice that had been genetically modified to have a resistance against asthma caused by rye grass pollen, and transplanted the bone marrow into unmodified mice.

"We take blood stem cells, insert a gene which regulates the allergen protein, and we put that into the recipient," says Steptoe.

"Those engineered cells produce new blood cells programmed to express the protein and target specific immune cells, which 'turn off' the allergic response."

Even though this study only looked at asthma, the researchers hope that the same approach could be used to provide protection against other common allergies - food and otherwise.

"Our work used an experimental asthma allergen, but this research could be applied to treat those who have severe allergies to peanuts, bee venom, shellfish and the like," Steptoe said.

But before we start throwing our puffers in the bin, the studies still have to be replicated in human trials, and that's where things get much more complicated.

"In the real world, unfortunately, it's not just usually a single allergen protein [that causes an immune response]. There might be several proteins that you might be allergic to and you'd have to target each of those proteins," Steptoe told ScienceAlert.

"We're currently doing experiments to see if we can turn off multiple response at the same time."

The research is published in JCI Insight.

Excerpt from:
Gene therapy has been used to 'switch off' asthma symptoms - ScienceAlert

By Laurie McginleyThe Washington Post

The oncologist was blunt: Stefanie Joho's colon cancer was raging out of control and there was nothing more she could do. Flanked by her parents and sister, the 23-year-old felt something wet on her shoulder. She looked up to see her father weeping.

"I felt dead inside, utterly demoralized, ready to be done," Joho remembers.

But her younger sister couldn't accept that. When the family got back to Joho's apartment in New York's Flatiron district, Jess opened her laptop and began searching frantically for clinical trials, using medical words she'd heard but not fully understood. An hour later, she came into her sister's room and showed her what she'd found.

"I'm not letting you give up," she told Stefanie. "This is not the end."

That search led to a contact at Johns Hopkins University, and a few days later, Joho got a call from a cancer geneticist co-leading a study there.

"Get down here as fast as you can!" Luis Diaz said. "We are having tremendous success with patients like you."

What followed is an illuminating tale of how one woman's intersection with experimental research helped open a new frontier in cancer treatment with approval of a drug that, for the first time, targets a genetic feature in a tumor rather than the disease's location in the body.

The breakthrough, now made official by the Food and Drug Administration, immediately could benefit some patients with certain kinds of advanced cancer that aren't responding to chemotherapy. Each should be tested for that genetic signature, scientists stress.

"These are people facing death sentences," said Hopkins geneticist Bert Vogelstein. "This treatment might keep some of them in remission for a long time."

A pivotal small trial

In August 2014, Joho stumbled into Hopkins for her first infusion of the immunotherapy drug Keytruda. She was in agony from a malignant mass in her midsection, and even with the copious amounts of OxyContin she was swallowing, she needed a new fentanyl patch on her arm every 48 hours. Yet within just days, the excruciating back pain had eased. Then an unfamiliar sensation hunger returned. She burst into tears when she realized what it was.

As months went by, her tumor shrank and ultimately disappeared. She stopped treatment this past August, free from all signs of disease.

The small trial in Baltimore was pivotal, and not only for the young marketing professional. It showed that immunotherapy could attack colon and other cancers thought to be unstoppable. The key was their tumors' genetic defect, known as mismatch repair (MMR) deficiency akin to a missing spell-check on their DNA. As the DNA copies itself, the abnormality prevents any errors from being fixed. In the cancer cells, that means huge numbers of mutations that are good targets for immunotherapy.

The treatment approach isn't a panacea, however. The glitch under scrutiny which can arise spontaneously or be inherited is found in just 4 percent of cancers overall. But bore in on a few specific types, and the scenario changes dramatically. The problem occurs in up to 20 percent of colon cancers and about 40 percent of endometrial malignancies cancer in the lining of the uterus.

In the United States, researchers estimate that initially about 15,000 people with this defect may be helped by this immunotherapy. That number is likely to rise sharply as doctors begin using it earlier on eligible patients.

Joho was among the first.

Even before Joho got sick, cancer had cast a long shadow on her family. Her mother has Lynch syndrome, a hereditary disorder that sharply raises the risk of certain cancers, and since 2003, Priscilla Joho has suffered colon cancer, uterine cancer and squamous cell carcinoma of the skin.

Stefanie's older sister, Vanessa, had already tested positive for Lynch syndrome, and Stefanie planned to get tested when she turned 25. But at 22, several months after she graduated from New York University, she began feeling unusually tired. She blamed the fatigue on her demanding job. Her primary-care physician, aware of her mother's medical history, ordered a colonoscopy.

When Joho woke up from the procedure, the gastroenterologist looked "like a ghost," she said. A subsequent CT scan revealed a very large tumor in her colon. She'd definitely inherited Lynch syndrome.

She underwent surgery in January 2013 at Philadelphia's Fox Chase Cancer Center, where her mother had been treated. The news was good: The cancer didn't appear to have spread, so she could skip chemotherapy and follow up with scans every three months.

By August of that year, though, Joho started having relentless back pain. Tests detected the invasive tumor in her abdomen. Another operation, and now she started chemo. Once again, in spring 2014, the cancer roared back. Her doctors in New York, where she now was living, switched to a more aggressive chemo regimen.

"This thing is going to kill me," Joho remembered thinking. "It was eating me alive."

Genetics meets immunology

Joho began planning to move to her parents' home in suburban Philadelphia: "I thought, 'I'm dying, and I'd like to breathe fresh air and be around the green and the trees.' "

Her younger sister wasn't ready for her to give up. Jess searched for clinical trials, typing in "immunotherapy" and other terms she'd heard the doctors use. Up popped a trial at Hopkins, where doctors were testing a drug called pembrolizumab.

"Pembro" is part of a class of new medications called checkpoint inhibitors that disable the brakes that keep the immune system from attacking tumors. In September 2014, the treatment was approved by the FDA for advanced melanoma and marketed as Keytruda. The medication made headlines in 2015 when it helped treat former President Jimmy Carter for melanoma that had spread to his brain and liver. It later was cleared for several other malignancies.

Yet researchers still don't know why immunotherapy, once hailed as a game changer, works in only a minority of patients. Figuring that out is important for clinical as well as financial reasons. Keytruda, for example, costs about $150,000 a year.

By the time Joho arrived at Hopkins, the trial had been underway for a year. While an earlier study had shown a similar immunotherapy drug to be effective for a significant proportion of patients with advanced melanoma or lung or kidney cancer, checkpoint inhibitors weren't making headway with colon cancer. A single patient out of 20 had responded in a couple of trials.

Why did some tumors shrink while others didn't? What was different about the single colon cancer patient who benefited? Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Hopkins, and top researcher Suzanne Topalian took the unusual step of consulting with the cancer geneticists who worked one floor up.

"This was the first date in what became the marriage of cancer genetics and cancer immunology," Pardoll said.

In a brainstorming session, the geneticists were quick to offer their theories. They suggested that the melanoma and lung cancer patients had done best because those cancers have lots of mutations, a consequence of exposure to sunlight and cigarette smoke. The mutations produce proteins recognized by the immune system as foreign and ripe for attack, and the drug boosts the system's response.

And that one colon-cancer patient? As Vogelstein recalls, "We all said in unison, 'He must have MMR deficiency!' " because such a genetic glitch would spawn even more mutations.

When the patient's tumor tissue was tested, it was indeed positive for the defect.

The researchers decided to run a small trial, led by Hopkins immunologist Dung Le and geneticist Diaz, to determine whether the defect could predict a patient's response to immunotherapy. The pharmaceutical company Merck provided its still-experimental drug pembrolizumab. Three groups of volunteers were recruited: 10 colon cancer patients whose tumors had the genetic problem; 18 colon cancer patients without it; and 7 patients with other malignancies with the defect.

The first results, published in 2015 in the New England Journal of Medicine, were striking. Four out of the 10 colon cancer patients with the defect and 5 out of the other 7 cancer patients with the abnormality responded to the drug. In the remaining group, nothing. Since then, updated numbers have reinforced that a high proportion of patients with the genetic feature benefit from the drug, often for a lengthy period. Other trials by pharmaceutical companies have shown similar results.

The Hopkins investigators found that tumors with the defect had, on average, 1,700 mutations, compared with only 70 for tumors without the problem. That confirmed the theory that high numbers of mutations make it more likely the immune system will recognize and attack cancer if it gets assistance from immunotherapy.

For Joho, now 27 and living in suburban Philadelphia, the hard lesson from the past few years is clear: The cancer field is changing so rapidly that patients can't rely on their doctors to find them the best treatments.

"Oncologists can barely keep up," she said. "My sister found a trial I was a perfect candidate for, and my doctors didn't even know it existed."

Her first several weeks on the trial were rough, and she still has some lasting side effects today joint pain in her knees, minor nausea and fatigue.

"I have had to adapt to some new limits," she acknowledged. "But I still feel better than I have in five years."

Excerpt from:
IT'S A START: Newly approved gene therapy may help 4 percent of cancer patients - Sarasota Herald-Tribune

The team hopes to develop a single, injected, gene therapy treatment that could eliminate many severe allergic responses (Credit: University of Queensland)

Scientists may be one step closer to discovering a way to genetically "turn off" allergic responses with a single injection. A team of researchers at the University of Queensland has developed a new process that has successfully silenced a severe allergic response in mice, using blood stem cells engineered with a gene that can target specific immune cells.

The big challenge previous allergy researchers faced was that immune cells, known as T-cells, tended to develop a form of "memory" so that once someone developed an immune response to an allergen, it would easily recur upon future contact. The key was finding a way to erase that "memory" response to the protein in the allergen causing the immune reaction.

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"We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient," says Professor Ray Steptoe, explaining the new process developed by his team at The University of Queensland. "Those engineered cells produce new blood cells that express the protein and target specific immune cells, 'turning off' the allergic response."

The team's initial clinical investigations looked at an experimental asthma allergen, with the new process found to successfully terminate established allergic responses in sensitized laboratory mice. While the initial research has focused on a very specific asthma allergen, Professor Steptoe believes the process could be applied to many other severe allergic responses, such as peanuts, bee venom and shell fish.

The long-term goal of the research would be to develop a therapy that could cure specific allergies with a single injection, much like a vaccine.

"We haven't quite got it to the point where it's as simple as getting a flu jab," says Professor Steptoe, "so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals."

The team is realistic about the time it will take before this discovery results in practical benefits for allergy sufferers, with at least five years more laboratory work needed before even human trials can be conducted. But this new discovery could mean that, within 10 or 15 years, asthma and other lethal allergic responses might be eliminated with a single, one-time treatment.

The findings were recent published in the journal JCI Insight.

Watch Professor Ray Steptoe from The University of Queensland discuss his team's findings in the video below.

Source: The University of Queensland

More:
Gene therapy could wipe immune memory and "turn off" severe allergies - New Atlas

Even as CDMO Lonza deals with FDA concerns about its cell manufacturing operationin the U.S., it has gone out and acquired a gene and cell contract manufacturer in Europe.

Lonza last week said it had acquired Netherlands-based PharmaCell for an undisclosed sum. It said the company had revenues of about 11 million last year. The company has a 15,500 cell manufacturing facility in Maastricht, The Netherlands, which can produce clinical through commercial-scale product.

Lonza said PharmaCell was primarily selected because of its expertise in autologous cell and gene therapy manufacturing, which includes experience with two licensedproducts in Europe.

"PharmaCells position in the market complements Lonzas leadership position in the allogeneic cell manufacturing market," Andreas Weiler, head of emerging technologies at Lonza said in a statement.

Autologous therapies use a patients own cells to create custom products as opposed to allogeneic therapies which can be manufactured in large batches from unrelated donor tissues such as bone marrow which can be used in off-the-shelf therapies. .

Loza said with this deal its gene therapy manufacturing network will span Europe, Asia and the U.S. It is Lonzas U.S. operation in the U.S. that recently ran into FDA concerns. Lonza had its cell therapy facility in Walkersville, Maryland,slapped with a warning letter in April after earlier halting some production of liquid media products being produced for a client.

The plant is overseen by the FDAs devices unit because its products are used for diagnostics. The letter said that retained samples were found to have Pantoea organisms that Lonza discovered after receiving two confirmed complaints for sterility failures of a of product.

A spokesperson said when the warning letter was issued that the company expects to have the problems resolved and FFM media manufacturing back online by mid-2017. The company had already begun a $7.6 million manufacturing upgrade at the facility, which is slated to be finished in 2018.

Originally posted here:
Lonza buys Dutch cell and gene therapy CMO - FiercePharma

May 30, 2017 08:05 ET | Source: Abeona Therapeutics Inc

NEW YORK and CLEVELAND, May 30, 2017 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq:ABEO), a leading clinical-stage biopharmaceutical company focused on developing novel gene therapies for life-threatening rare diseases, announced today that the FDA has granted Rare Pediatric Disease Designation for Abeonas EB-101 gene therapy program for patients with dystrophic epidermolysis bullosa (DEB), including recessive dystrophic epidermolysis bullosa (RDEB), which are life-threatening genetic skin disorders characterized by skin blisters and erosions that cover the body.

These designations are granted to drugs with high promise that may address areas of unmet medical need for children with rare diseases. RDEB is a debilitating and life threatening inherited disorder with no approved treatment options available for patients today," stated Timothy J. Miller, Ph.D., President & CEO of Abeona Therapeutics Inc. Building upon the already granted FDA and EMA Orphan Drug Disease Designations for the EB-101 gene therapy program, receiving the Rare Pediatric Disease Designation is another important validation of the science and clinical approach to developing a novel gene therapy for RDEB patients.

Typically, wounds on patients with RDEB, also known as "butterfly skin" syndrome, can remain unhealed for months to years due to the inability of the skin to stay attached to the underlying dermis and can cover a large percentage of the body. In the ongoing Phase 1/2 clinical trial, EB-101 was administered to non-healing chronic wounds on each subject and assessed for wound healing at predefined time points over years. The primary endpoints of the clinical trial assess safety and evaluate wound healing after EB-101 administration compared to control untreated wounds. Secondary endpoints include expression of collagen C7 and restoration of anchoring fibrils at three and six months post-administration.

About Rare Pediatric Disease Designation: The rare pediatric disease designation indicates that the FDA may give the company a pediatric priority review voucher if the drug is approved for the pediatric indication. That voucher could then be used by the company for another drugany drugto be given a priority review. A priority review mandates that the FDA will review a BLA drug submission within six months instead of the standard 10 months. Normally, a priority review designation would only be given to a drug that is for a serious condition and has demonstrated the potential to be a significant improvement in safety and effectiveness. The priority review voucher may be used by the sponsor, sold or transferred.

EB-101 Gene Therapy Program Highlights:

About EB-101: EB-101 is an autologous, ex-vivo gene therapy in which COL7A1 is transduced into autologous keratinocytes for the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB). RDEB is a subtype of an inherited genetic skin disorder characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with RDEB lack functional type VII collagen owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils, which stabilize the dermal-epidermal basement membrane. Patients are being enrolled in the ongoing Phase 2 portion of the Phase 1/2 clinical trial (NCT01263379). The EB-101 program has also been granted orphan drug designation by the FDA and European Medicines Agency (EMA).

About Epidermolysis Bullosa (EB): EB is a group of devastating, life-threatening genetic skin disorders that is characterized by skin blisters and erosions all over the body. The most severe form, recessive dystrophic epidermolysis bullosa (RDEB), is characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with RDEB lack functional type VII collagen (C7) owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils that attach the dermis to the epidermis. EB patients suffer through intense pain throughout their lives, with no effective treatments available to reduce the severity of their symptoms. Along with the life-threatening infectious complications associated with this disorder, many individuals often develop an aggressive form of squamous cell carcinoma (SCC).

About Abeona: Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene therapies for life-threatening rare genetic diseases. Abeona's lead programs include ABO-102 (AAV-SGSH), an adeno-associated virus (AAV) based gene therapy for Sanfilippo syndrome type A (MPS IIIA) and EB-101 (gene-corrected skin grafts) for recessive dystrophic epidermolysis bullosa (RDEB). Abeona is also developing ABO-101 (AAV-NAGLU) for Sanfilippo syndrome type B (MPS IIIB), ABO-201 (AAV-CLN3) gene therapy for juvenile Batten disease (JNCL), ABO-202 (AAV-CLN1) for treatment of infantile Batten disease (INCL), EB-201 for epidermolysis bullosa (EB), ABO-301 (AAV-FANCC) for Fanconi anemia (FA) disorder and ABO-302 using a novel CRISPR/Cas9-based gene editing approach to gene therapy for rare blood diseases. In addition, Abeona has a plasma-based protein therapy pipeline, including SDF Alpha (alpha-1 protease inhibitor) for inherited COPD, using its proprietary SDF (Salt Diafiltration) ethanol-free process. For more information, visit http://www.abeonatherapeutics.com.

Investor Contact: Christine Silverstein Vice President, Investor Relations Abeona Therapeutics Inc. +1 (212)-786-6212 csilverstein@abeonatherapeutics.com

Media Contact: Andrea Lucca Vice President, Communications & Operations Abeona Therapeutics Inc. +1 (212)-786-6208 alucca@abeonatherapeutics.com

This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, the expected receipt of a Priority Review Voucher and that involve risks and uncertainties. These statements include, without limitation, our plans for continued development and internationalization of our clinical programs, that patients will continue to be identified, enrolled, treated and monitored in the EB-101 clinical trial, and that studies will continue to indicate that EB-101 is well-tolerated and may offer significant improvements in wound healing. These statements are subject to numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the impact of competition; the ability to develop our products and technologies; the ability to achieve or obtain necessary regulatory approvals; the ability to secure licenses for any technology that may be necessary to commercialize our products; the impact of changes in the financial markets and global economic conditions; and other risks as may be detailed from time to time in the Company's Annual Reports on Form 10-K and other reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise.

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Abeona Therapeutics Receives Rare Pediatric Disease Designation ... - GlobeNewswire (press release)

1) Germ Line Gene Therapy: This process involves the altering of a baby's the genome before it has even been born. The gene may be inserted through Germ line gene therapy is still an emerging technique that needs to be perfected before being tested on humans. Germ line therapy is also, a more challenging than the more common somatic cell gene therapy. However, germ line therapy raises concerns regarding ethics and morality. The two main methods of performing germ-line gene therapy would be:

(Citation 17) (Citation 17) 2) Somatic Cell Gene Therapy: The most studied gene therapy, somatic cell therapy uses the insertion of a normal gene into the DNA of somatic cells in order to compensate for the non-functioning defective gene. Which can be done in a number of ways including:

(Citation 17) Virus Vectors: Both Somatic and Germ line gene therapy, need a way to insert DNA into a cell therefore carrier molecule called a vector must be used to deliver the therapeutic gene to the patient's target cells. The most efficient and effective vectors to date are viruses. Viruses can be genetically altered to carry normal human DNA, then passing on the healthy genes to human cells. Much like a chauffeur who picks up and delivers people to certain locations. Some examples of viruses that are used as vectors are: Retroviruses, Retroviruses, Adeno-associated viruses, and Herpes simplex viruses.

In Vivo Vs. Ex Vivo

(Citation 17)

3) Chimeraplasty : This technique is the least known of all three methods. It is a non- viral method that is still being researched for its potential in gene therapy. Chimeraplasty is done by changing DNA sequences in a person's genome using a synthetic strand composed of RNA and DNA. This strand of RNA and DNA is known as a chimeraplast. The chimeraplast enters a cell and attaches itself to the target gene. The DNA of the chimeraplast and the cell complement each other except in the middle of the strand, where the chimeraplast's sequence is different from that of the cell. The DNA repair enzymes then replace the cells DNA with that of the chimeraplast. This leaves the chimeraplast's new sequence in the cell's DNA and the replaced DNA sequence then decays.

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Gene Therapy

MOUNTAIN VIEW, CA--(Marketwired - May 15, 2017) - SENS Research Foundation (SRF) has launched a new research program focused on somatic gene therapy in collaboration with the Buck Institute for Research on Aging. Brian Kennedy, PhD, a leading expert on the biology of aging, will be running the project in his lab at the Buck.

Many potential treatments of age-related diseases require the addition of new genes to the genome of cells in the body, a technology known as somatic gene therapy. The technology has been hampered, up until now, by the inability to control where the gene is inserted. That lack of control resulted in a significant risk of insertion in a location that encourages the cell to become malignant.

SRF has devised a new method for inserting genes into a pre-defined location. In this program, this will be done as a two-step process, in which first CRISPR is used to create a "landing pad" for the gene, and then the gene is inserted using an enzyme that only recognizes the landing pad. SRF has created "maximally modifiable mice" that already have the landing pad, and this project will evaluate how well the insertion step works in different tissues.

"Somatic gene therapy has been a goal of medicine for decades. Being able to add new healthy genes will enable us to address treatments of such age-related diseases as atherosclerosis and macular degeneration. Our collaboration with SRF will substantially move us toward finding effective treatments to genetically based age-related diseases," said Dr. Kennedy.

"Partnering with Brian Kennedy and the Buck enables SRF to continue towards our goal of achieving human clinical trials on rejuvenation biotechnologies in the next five years. Brian's leadership in moving this technology into mammals is a huge step forward," said Dr. Aubrey de Grey, CSO, SENS Research Foundation.

This research has been made possible through the generous support of the Forever Healthy Foundation and its founder Michael Greve, as well as the support of our other donors. The Forever Healthy Foundation is a private nonprofit initiative whose mission is to enable people to vastly extend their healthy lifespans and be part of the first generation to cure aging. In order to accelerate the development of therapies to bring aging under full medical control, the Forever Healthy Foundation directly supports cutting-edge research aimed at the molecular and cellular repair of damage caused by the aging process.

About SENS Research Foundation (SRF)SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop, and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF is focused on a damage repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education. SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as macular degeneration, heart disease, cancer, and Alzheimer's disease. Educating the public and training researchers to support a growing regenerative medicine field are also major endeavors of the organization that are being accomplished though advocacy campaigns and educational programs. For more information, visit http://www.sens.org.

About Buck Institute for Research on AgingBuck Institute is the U.S.'s first independent research organization devoted to Geroscience -- focused on the connection between normal aging and chronic disease. Based in Novato, California, the Buck is dedicated to extending "healthspan," the healthy years of human life, and does so by utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and others focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org.

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SENS Research Foundation Announces New Research Program on Somatic Gene Therapy With Buck Institute for ... - Markets Insider

Isarna Therapeutics showed off positive Phase I data for its lead compound ISTH0036 in patients with Glaucoma at the ARVO meeting last week.

Isarna Therapeutics from Munich is developing TGF- specific antisense RNA therapeuticsto treat ophthalmic and fibrotic diseases and cancer.Now the company hascleared its first Phase I trial for its lead candidate ISTH0036 in patients with advancedglaucoma. Additionally, the company is set to expand into further indications, with preclinical data demonstrating the drugs potential in models of age-related macular degeneration (AMD) and diabetic macular edema (DME).

We are now moving towards Phase II development in advanced glaucoma but also other TGF-2 associated diseases such as wet Age-related Macular Degeneration (AMD) and other TGF2-associated diseases such as Diabetic Macular Edema (DME), well supported by the recent preclinical data we could gather for these diseases,commented Eugen Leo, Head of Clinical Development at Isarna.

In glaucoma, the second leading cause of vision impairment, thebuild-up of fluid in the eye leads to an increased intraocular pressure (IOP) that eventually damages the optic nerve.Scientific data indicates that disease progression is associated with elevated levels of TGF-2 that result in alterations of the trabecular network and potentially direct toxic effects on the optic nerve.

ISTH0036 is an antisense oligonucleotide targeting the mRNA of TGF-2, thereby inhibiting its transcription. The new Phase I study revealed that the gene therapy wassafe and well-tolerated in all patients and even demonstrated preliminary evidence for clinical efficacy regarding postoperative control of intraocular pressure (IOP).

Isarnas antisense RNA approach is very different from currently approved treatments for glaucoma, which includebeta blockers and alpha agonists thatboth work by reducing the production of intraocular fluid. However, French Eyevensys, which we interviewed last week at BioTrinity,is going for a similar strategy. The company just started clinical development of its lead compoundEYS606,a plasmid which encodes for an anti-TNF drug to treat patients with non-infectious uveitis. Similar to Isarna, the company is planning to expand its indications to address a number ophthalmic conditions such as AMD and DME.

Although the AMD market is expected to reach a whopping$8Bby 2020, the competition within this field is fierce, with big players like Regeneron and Roche dominating both AMD and DME markets with their effective VEGF-inhibitors Eyelea and Lucentis, respectively.

Images via shutterstock.com /photoJS and Mrs_Bazilio

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After deals and acquisitions with Spark Therapeutics and Bamboo, Pfizer is once again looking to bolster its rare and gene therapy pipeline as it outlines a new drug pact with Sangamo.

The collaborationlicense agreement focuses on the development and eventual sale of the biotechs gene therapy programs for hemophilia A, including SB-525, one of Sangamos four lead product candidates.

This early candidate is slated to enter the clinic this quarter, centering on testing safety as well as blood levels of Factor VIII protein, and other efficacy endpoints.

Sangamo gets $70 million upfront from the Big Pharma, and could gain $475 million in biobucks and sales royalties on any medications from the collaborationthat gain approval.

Under the deal, Sangamo will take the lead on the SB-525 phase 1/2 test as well as unspecified manufacturing activities.

Pfizer, meanwhile, will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for the therapy, as well as any additional products, if any.

Sangamo will also work with Pfizer on manufacturing and technical ops using viral delivery vectors.

SB-525 works as a AAV vector carrying a Factor VIII gene construct driven by a synthetic, liver-specific promoter. The FDA has already cleared the start of human trials for SB-525, and given it an orphan drug tag.

The deal has proved powerful for Sangamo, with its shares jumping 44% after hours on the news last night.

This marks another step into the new world of gene therapies for Pfizer, coming less than a year after its $700 million buy of Bamboo Therapeutics, adding advanced recombinant adeno-associated virus (rAAV)-based gene therapies to its pipeline.

It also has a long-standing deal with Spark Therapeutics, in hemophilia, penned in 2014. Back in January, Pfizer in fact paid a $15 million milestone bonus to Spark for hitting its marks in the ongoing hemophilia B phase 1/2 trial FDA breakthrough-tagged SPK-9001.

Pfizer also has a series of preclinical gene therapies, including a neuromuscular candidate for Duchenne muscular dystrophy (DMD), as well as preclinical candidates to treat Friedreichs ataxia and Canavan disease, and a phase I candidate for giant axonal neuropathy.

Pfizer also gained an operating gene therapy manufacturing facility that Bamboo bought from the University of North Carolina last year.

The pharma also has several academic research agreements, including one with Kings College London to develop a series of rAAV gene therapy vectors and another with the University of Iowa Research Foundation to develop a potential gene therapy for cystic fibrosis.

And its partnered with Emeryville, CA-based Molecular Therapeutics (4DMT) to discover and develop targeted next-generation rAAV vectors for cardiac disease; it made an investment in the company a few years back.

Once seen as the next big thing in research, gene therapies have however come under pressure in recent months about just how viable they are on the market. After struggling for years to make a commercial success out of Glybera, the worlds first approved gene therapy, uniQure recently called it quits on the treatment.

The drugmaker said it wouldnt bother asking European authorities to renew the $1-million-plus gene therapys marketing authorization when it expires in October, and comes after it abandoned plans to gain an approval in the U.S. Reports from MIT Technology Review suggest only one patient ever used the med.

GlaxoSmithKline has also been struggling in Europe with its bubble boy syndrome gene therapy Strimvelis. Mindful of Glyberas cost, GSK put its price tag at half that of Glybera, at $665,000, and also offered a money-back guarantee.

Its been approved in Europe for nearly a year, but it only treated its first patient this month, according to Business Insider.

Treatment is tough as the drug is not so much manufactured as it is created for each individual patient, with a site in Italy currently the only approved site in the world for this type of manufacture, and thus the only place where patients can be treated. Only around 15 patients in Europe are believed to have the condition.

Other biotechs are however working on the manufacturing side in order to try and make these therapies more available for patients, and thus open up their viability.

There are already a number of medications on the market for hemophilia, such as from Biogen spin-off Bioverativ and Sobi, with gene therapy predicted by some also working in the space, including uniQure and BioMarin, to be the next class for treating the blood disorder.

But speaking to FierceBiotech at the start of the year, Bioverativs new chief and former Biogen exec John Cox told me that while they are to working on gene therapy approaches to hemophilia, there are reasons to be cautious: There are of course question marks over gene therapy: The obvious one is safety, because of the history here, and this is a risk-averse population, for good reason, and the other question is naturally over efficacy, and how long does it last, as well as manufacturing, scale and so on.

Were all hoping for a cure, and of course were doing work on gene therapy now, but I dont think people are looking at these now as a permanent cure; the questions are over durability, rather than cure.

He said that investors and even doctors talk a lot about gene therapy in the hemophilia space, but that if you talk to hemophilia A patients about what they really want, being able to dose, once a week [which is the target with its candidate, or even just less frequently, is what they want.

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New step toward the treatment of myotubular myopathy gene therapy restores strength and prolongs lives in affected ... Science Daily A team of researchers in France, led by Dr. Ana Buj-Bello (Genethon/Inserm) and teams at the University of Washington and Harvard Medical School in the United States, achieved a new step towards the treatment of myotubular myopathy by gene therapy. and more »

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Xconomy San Diego

Christopher Reinhard will tell you there is nothing unusual about the 20-plus years hes spent getting an experimental heart therapy to late-stage clinical trials.

Very rarely will you get a short story on development of a drug, said Reinhard (above), who is a principal investor and the CEO of San Diego-based Angionetics. Two decades is about what you would expect for a new drug-making method, Reinhard said.

That may be true, but it doesnt begin to convey the tortuous path that Reinhard has followed to get Angionetics where it is today. The biotech is starting a phase 3 trial in the next few months that seeks to enroll some 320 patients with myocardial ischemiawhen clogged coronary arteries reduce the flow of oxygen-rich blood to the heart.

To treat the disease, Angionetics isnt testing some new type of cholesterol-lowering drug, or a stent to help open clogged arteries.

Rather, its attempting a risky and less-proven methodgene therapy, in which new genetic instructions are transported into the body to help produce a specific protein. Gene therapies have been in development for decades, but are only now starting to come of age thanks to a variety of technological advances. Two therapies are approved in Europe, from UniQure (NASDAQ: QURE) and GlaxoSmithKline, both for ultra rare immune and metabolic diseases. Spark Therapeutics (NASDAQ: ONCE) this year is expected to file the first ever U.S. approval application for a gene therapy, a treatment for a form of childhood blindness.

Angionetics gene therapy, Ad5FGF-4 (Generx), is intended to stimulate the growth of new blood vessels in the heart. A catheter inserted through the groin delivers the genescarried within modified virusesinto heart cells, where they are supposed to produce a protein, fibroblast growth factor-4, that helps grow new blood vessels.

The hope is to ease chest pain and relieve the effects of clogged coronary arteries by stimulating the growth of new blood vessels in areas in the heart where there is insufficient blood flow. Were just taking the heart and trying to enhance its ability to grow more blood vessels, Reinhard said.

Angionetics image highlights growth of collateral blood vessels (Image by Bryan Christie Design, used with permission)

While gene therapies are more advanced than ever, and several experimental treatments aimed at heart disease and heart failure are being tested, none have yet succeeded. A heart failure gene therapy from San Diegos Celladon, for instance, failed in 2015.

Still, the potential prize is substantial. Of the estimated 16.5 million Americans with coronary heart disease, Angionetics Reinhard said about half experience heart-related chest pain.

The current standard of care offers two principal methods of treatment. The first course of therapy is usually to prescribe drugs like nitrates that temporarily dilates blood vessels to Next Page

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788

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Angionetics Nears Key Gene Therapy Trial for Coronary Heart Disease - Xconomy

Dimas Padilla, 43, of Kissimmee, is in remission from non-Hodgkin's lymphoma after receiving an experimental cancer therapy called CAR-T. Here, he poses with his wife, Dimas Padilla. NBC News

"These are patients who really are without hope," Locke said.

"Patients who at best could expect to have a one in 10 chance of having a complete disappearance of their lymphoma," he added. "So the results are really exciting and remarkable."

More than 80 percent of the 101 patients who got the treatment were still alive six months later. "Only about half the patients who (went) on this study could expect to even be alive six months after the therapy," Locke said.

Padilla is one of them. When the cancer came back most recently time, his lymph nodes were bulging. "They were so bad that they moved my vocal cords to the side and I was without my voice for almost three months," he said.

"They kept growing and my face was swelling, and I thought I was going to choke while I was sleeping."

Padilla was among the last patients enrolled in the trial.

"Once they infused the cells in my body, within two to three days all my lymph nodes started melting like ice cubes," he said.

The treatment is no cake walk. Just as with a bone marrow transplant, the patient's immune system must be damaged so that the newly engineered T-cells can do their work. That involves some harsh chemotherapy.

It's so harsh that it killed three of the patients in the trial. Padilla says he still has some memory loss from his bout with the chemo.

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"I had some fevers and I was shaking and a little bit of memory loss but it was temporary," he said. "I will say that it was pretty intense for like a week, but in my second week, second week and a half, I was starting to feel more normal. I was able to start walking and the shaking was not as bad as it was in the beginning," he said.

And when he got the news that his lymphoma was gone at least for now Padilla was delighted.

"I kissed my wife. I probably kissed the doctor," he said.

The company developing the treatment, Kite Pharma, sought Food and Drug Administration approval for the therapy on Friday.

It carries the tongue-twisting name of axicabtagene ciloleucel, and it's the first commercial CAR-T product to get into the FDA approval process.

It's far too early to say any of the patients were cured, Locke cautions. And such a difficult treatment course is really only for patients in the most desperate condition.

"The patients in this trial were really without options," he said.

But Locke is sold on the approach. "This is a revolution. It's a revolution in cancer care. This is the tip of the iceberg," he said.

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New Gene Therapy for Cancer Offers Hope to Those With No ... - NBCNews.com

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February is National Cancer Prevention Month. It's a disease that more than a million Americans are diagnosed with each year, according to the National Cancer Institute. This morning in our special series "War on Cancer," TODAY takes a look at the latest advances in the fight against this deadly disease.

Celine Ryan, a 51-year-old engineer and mother of five, was diagnosed with stage 4 colon cancer three years ago. After undergoing surgery, radiation and chemotherapy, doctors discovered cancer in her lungs seven tumors that threatened her life.

Ryan, who lives in Michigan, read about a clinical trial using gene therapy at the National Cancer Institute in Bethesda, Maryland, and decided to apply. The trial is headed up by Dr. Steven Rosenberg, a leading researcher in immunotherapy at the institute. She decided the treatment would be a birthday present to herself.

Getting into the trial wasn't simple because her tumors, though numerous, weren't large enough for the form of treatment being tested, but she was finally accepted in March 2015.

RELATED: Keytruda, the drug that helped Jimmy Carter, also can stop lung cancer

The treatment involves removing cells from a tumor your body's own cancer-fighting cells multiplying them by billions in a lab, then returning them back to your body to fight the tumor.

Celine Ryan is being referred to as an historic figure in medicine.

After spending a month in the hospital and letting the treatment run its course, six of her seven tumors had completely disappeared. The last tumor started to grow eight or nine months later and the decision was to remove it through surgery.

RELATED: 10 things I wish I knew before I was diagnosed with breast cancer

The treatment isn't widely available now, and not all patients experience the positive results Ryan had.

"Many have not responded," Rosenberg said. "But from every patient that we treat, whether... their cancers go away or not, we learn something."

Today, Celine Ryan is ten months cancer-free.

Thanks to Ryan's unusual genetic makeup, researchers were able to identify how to attack the mutation that causes common cancers. This experimental treatment may not be the solution for everyone, but for Ryan, it's meant ten months of being cancer-free.

"We can do, and are planning to do, that kind of gene therapy using the exact receptor we got from Celine's cells to treat other people," Rosenberg explained.

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The experimental gene therapy treatment that helped one woman fight cancer - Today.com

Xconomy Boston

Despite the early and in some cases stunning results produced by gene therapy treatments in handfuls of hemophilia patients, significant questions remain about their durability, safety, and how broadly theyll be used if they are ultimately shown to work. The first human data produced by Dimension Therapeutics, one of several companies developing hemophilia gene therapies, are the latest example.

Shares of Cambridge, MA-based Dimension (NASDAQ: DMTX) tumbled more than 49 percent on Tuesday on early data from a Phase 1/2 trial of DTX101, its experimental gene therapy for hemophilia B.

DTX101 boosted the levels of the blood-clotting protein Factor IX in six patients. Those on the higher of two tested doses havent needed other drugs since getting treatment. But five of the six patientsand all three on the higher of the two tested dosesalso saw a rise in liver enzyme levels, indicating an immune reaction to the gene therapy. While none of the five patients have had any safety problems, the liver enzyme spikes have caused a delay for Dimension. The company wont test an even higher dose of DTX101 in patients until it gets feedback from the FDA.

Gene therapy offers the potential of a long-lasting, if not permanent treatment for hemophilia patients, whodepending on how severe their disease ismay need frequent infusions of preventative drugs to stave off dangerous bleeds. A group of experimental gene therapies have been creeping their way forward in clinical trials, accumulating data in dribs and drabs. Spark Therapeutics (NASDAQ: ONCE) and UniQure (NASDAQ: QURE) are the furthest along in hemophilia B, while BioMarin Pharmaceutical (NASDAQ: BMRN) leads the way in the more common hemophilia A.

Each experimental therapy has shown promise helping patients produce meaningful levels of the clotting proteins Factor IX and Factor VIII, respectivelymore than 5 percent of the levels found in normal patients, which many view as the minimum bar for successover the course of a year or more. And Spark and BioMarin have seen much higher numbers than that, in some cases. But there are caveats: Those results have come in small sample sizes, and they have varied patient to patient. Data today from Dimension show the three patients on a low dose of DTX101 had roughly 3 to 4 percent of normal Factor IX levels a year after treatment. The results are earlier for those on a higher dose: 5 and 8 percent, respectively, for two patients 12 weeks post-treatment; 7 percent for a third patient 7 weeks after DTX101.

Additionally, so far, liver enzyme increases have been seen in clinical tests for each of the hemophilia gene therapies. Such increases could indicate that patients immune systems were attacking their liver cells, which are the ones that take up the therapeutic gene and churn out the new clotting protein. Theyre typically treated with a short course of immunosuppressive steroids and havent caused bad side effects so far. But in some cases theyve stifled a response to gene therapy, which is important because it means that certain gene therapies may not workor at least wont work as well as they couldfor some patients who develop neutralizing antibodies. It also means that patients who develop those antibodies wont be eligible for a second dose if the gene therapy wears off. This phenomenon reduces the potential market for the firms developing hemophilia gene therapies. Such immune responses were the impetus behind a deal Spark cut last year with Selecta Biosciences (NASDAQ: SELB), for example.

We continue to explore the therapeutic window for DTX101 as our data mature and in light of the [liver enzyme] rises that appear to be associated with a decline in [Factor IX] activity, CEO Annalisa Jenkins said in a statement.

Heres more on Dimension, and the technical differences between each of the companies developing gene therapies for hemophilia.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com

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Investors Sour on Data Debut For Dimension's Hemophilia Gene Therapy - Xconomy

The hottest biotechs in the field of hemophilia are stealing the show at this years edition of the EAHAD hemophilia congress in Paris.

A disorder for which no cure is available, hemophilia is caused by absent or defective genes coding for blood clotting factors, turning simple injuries intohealth risks and causing spontaneous bleeding. Researchers and companies worldwide working to improve hemophilia therapy are meeting this week in Paris for the10th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD).

We recently reviewed the latest advances in hemophilia, a field teeming with innovative solutions and technology.Among the most interesting presented at the congress are new results on gene therapy and RNAi, a pen to treat hemophilia and many companies fighting to reduce thedosing frequency of prophylactic therapy. On top of that, Shire has reported that current estimates of people suffering from the disease could be completely wrong

Novo Nordisk ismaking plans to use its famous insulin pens to deliver hemophilia drugs. According to astudy evaluating user experience with the pens presented at the congress, participants liked the device as it is easy to use, well designed, more portable and involving fewer steps than their current kits for hemophilia.

The ultimate goal of the Danish company is to use its FlexTouch pen to deliverconcizumab, an antibody againsttissue factor pathway inhibitor (TFPI) currently in Phase I for both hemophilia A and B.

Shire has presented a study revealing that the incidence of hemophilia could be more than three times higherthan current estimates. It also showed that only 25% of hemophiliacs receive adequate treatment. These findings might push efforts to put an end to this situation and stimulate market growth.

Shirepresented positive results from a Phase II/III trial for Adynovate (BAX 855) in children with hemophilia A. Interestingly, the company also showed early stage in vitro results for combination therapies with a biosimilar of Roches emicizumab (ACE910). It looks like the antibody, not yet in the market, already has strong competitors getting ready for when its patent expires.

Sobi, inSweden, has co-developed recombinant clotting factors with an extended half-life in partnership with Biogens spin-offBioverativ. To do so, they fuse the clotting factor to the Fc portion immunoglobulin G1 proteins.

The team has presented positive long-term safety and efficacy results forEloctatein hemophilia A andAlprolixin hemophilia B. Both are already in the market and reduce dosing frequency to weekly injections.

OPKO Biologics, in Israel, follows a strategy similar to Sobis. ItsCTP technologyextends the half-life of proteins by fusing them with theC-terminal peptide of human chorionic gonadotropin (hCG).

The company has presented data forMOD-5014(FVIIa-CTP) supporting the advance intoPhase II/IIItrials. The drug is intended for delivery twice a week, which is double of that from Sobis products.

Spark Therapeuticsis one of the leaders in the development ofgene therapy for hemophiliaanduniQures main competitor. The American company will report results from itsPhase I/IItrial forSPK-9001in hemophilia B showing sustained activity of the therapy after12 weeks, with only one reported bleeding.

Despite good results, Spark is facing strong competition from the DutchuniQure. Its gene therapyAMT-060has already shown sustained effects for at least52 weeksin a patient subpopulation. Both companies nowhavebreakthrough designation from the FDA and therace to reach the market is tight.

Sanofis partner, Alnylam, is conducting clinical trials across the UK, Switzerland and Bulgaria to test its unique RNAi technology for hemophilia. Its candidate fitusiran, which blocks antithrombin to improve clotting,is proving safe and effective inPhase I/IItrials.

This unique treatment has the potential to reduce dosing to a monthly basis and is suitable for patients with both hemophilia A and B, also including those that have developed resistanceto standard treatments.

Among the companies presenting are many others includingGenentech, Bayer and Catalyst Biosciences. The sheer number of innovative approaches under development is great news. Such a wide arrange of solutions could provide a better quality of life for hemophilia patients, each treatment suited for the particular needs of differentpatients. Especially now that, thanks to Shire, scientists know the number of patients suffering from the condition could actually be much higher.

Images from Sashkin, nobeastsofierce, Roberta Canu, Mond Duang,Art tools, LeonP,Pakpoom Nunjui /Shutterstock.com

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Gene Therapy, RNA and Pens at European Hemophilia Congress in Paris - Labiotech.eu (blog)

By the time 2-year-old Calliope Joy Carr, of Bala Cynwyd, was diagnosed with an incurable degenerative brain disease, two children with the same deadly ailment, just 20 miles away, were being offered a tenuous lifeline.

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Eli and Ella Vivian, 7- and 4-year-old siblings from Upper Providence Township, also had metachromatic leukodystrophy, a genetic disease that robs its victims, mostly children, of their motor and mental skills and, eventually, their lives. But because their symptoms were less severe than Calliope's, the Vivian children were eligible for a gene therapy clinical trial in Milan, Italy, that she was not.

Today, at 7, Calliope is bedridden, able to smile at her family and favorite TV programs and move her head slightly, but unable to speak. MLD continues to take its toll, as well, on Eli and Ella Vivian, 11 and 8. But they attend school, play, and are rambunctious in a way that Calliope has not been since three months after her diagnosis, when she spoke for the last time, saying "Daddy."

Eli and Ella "shouldn't be able to do what they are doing," said their mother, Becky Vivian. "We have hope and we are grateful, but we are realistic. It may not save their lives, just prolong it."

One in 40,000 infants is born with MLD. Now, gene therapy - the transfer of normal genes into cells to replace missing or defective ones - is engendering hope in families that their children can be more effectively treated, if not as yet cured.

Other recent developments have further boosted that optimism.

Alessandra Biffi, the physician/researcher who led the trial at Milan's San Raffaele Hospital, now directs the gene therapy program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Further, the experimental treatment has been licensed by GlaxoSmithKline, which has major operations in Philadelphia. And the Leukodystrophy Center at Children's Hospital of Philadelphia, opened in 2015, is delivering cutting-edge care.

Andrew Shenker, vice president in GSK's rare diseases unit and project physician leader for its MLD program, cautions that the research begun in Italy in 2009 is ongoing. The pharmaceutical company expects to submit data from the trial to government regulators in 2018, after which those agencies will conduct their own reviews.

Children with MLD lack an enzyme in key cells needed for the production and maintenance of myelin, which protects nerves and facilitates the transmission of impulses within the brain. Without myelin, communication is disrupted. The patient loses basic functions, resulting in paralysis, blindness, seizures, and eventual death.

The condition is passed down from two carrier parents; any child they produce has a 1 in 4 chance of having the disease. Survival ages vary, depending on when MLD is discovered and the level of medical care. In the absence of treatment, the mean age of death for a child diagnosed at 1 to 2 years of age is 4.2 years; for those diagnosed between 4 and 14, the mean age is 17.4 years.

The most common form of treatment is stem cell therapy, but results have been "mixed" and "disappointing," Shenker said.

Other researchers are investigating treatments including enzyme replacement and gene therapy, and screening procedures to diagnose the disease at birth, said Dean Suhr, president of the Oregon-based MLD Foundation.

Results published so far on the Milan trial indicate that when treatment is administered before patients show obvious signs of the disease, the onset of symptoms is delayed, and their severity lessened.

Gene therapy appears most effective with children diagnosed before age 2 and treated before they show symptoms, Shenker said. Research on the treatment's benefit for older youngsters is ongoing.

Two children who were treated after the onset of symptoms died while participating in the trial, but their deaths were attributed to the progression of the disease, not the safety of the closely-monitored treatment, Shenker said.

Ella Vivian was one of the test cases. Because his symptoms were more advanced than hers, Eli was not part of the trial, but was treated under a "compassionate use protocol." The Inquirer published an article about the siblings in January of 2013 before the family left for Italy.

They spent six months in Milan, during which they received massive doses of chemotherapy to kill the diseased stem cells and make room for new cells containing the healthy gene to take hold. Researchers used a form of the HIV virus, minus the disease component, as a transfer agent to insert the genes.

Becky Vivian, 44, a Gymboree teacher, accompanied her children to Milan, while husband Steve stayed home with older sons Eric and Evan.

"Right now, we know they are a miracle," she said. ". . . Unfortunately, we can still see progression of the disease, albeit slowly."

Eli has difficulty standing up straight and walking, and cannot run. Ella has pain in her arms and legs, and her walking is getting slower, her writing less legible.

They have regular physical and occupational therapy, but are on no medication, their mother said. They also return to Milan every six months for checkups. In several weeks, they will be visiting Biffi in Boston for testing.

The Vivian siblings give Calliope's parents hope - if not for their daughter, then for other children with the disease and those diagnosed in the future.

Calliope, called "Cal," was diagnosed at 21/2, shortly after her parents noticed she was losing her balance on stairs.

"When we found out Cal was sick, we were really lost," said her mother, Maria Kefalas, 49, a sociology professor at Saint Joseph's University.

Three months later, Cal said her last word.

"It was like she fell off a cliff," said her father, Patrick Carr, 50, an associate professor and director of the Criminal Justice Program at Rutgers University-New Brunswick.

Cal has been in hospice care for four years, but the little girl her family knew at 2 is still there, Carr says. She loves her favorite TV shows and dolls, and smiles when brother P.J., 12, gets scolded.

Shortly after their daughter was diagnosed, Kefalas and Carr created the Calliope Joy Foundation, which has raised $300,000 - much of it by selling cupcakes - for research and patient care, including $60,000 for the Leukodystrophy Center of Excellence. The annual fund-raiser is May 6 at Lincoln Financial Field.

The charity also supports families like the Vivians, who got a donation to help with travel to Italy.

Becky Vivian says she is in a desperate race to save her children. And the family isn't letting up.

When Eli struggles with a tall chair and asks for a boost, his mother says no.

"Once we give in, it'll be time for a wheelchair. So I say, 'Eli, you've got to do it yourself.' "

kholmes@phillynews.com

610-313-8211

For information on the Calliope Joy Foundation, visit http://www.thecalliopejoyfoundation.org/

For updates on the Vivian children, visit http://www.facebook.com/Eli-Ellas-Prayer-Warriors-393482210723355/

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The promise of gene therapy for Eli and Ella, but not ...