StemCell Therapy

Human protein-coding genes number from 20,000 up to 25,000.

If just one of these genes gets altered or a code gets missing, it can be fatal to an individual.

In fact, approximately 30 per cent of infant mortality at birth in developed countries are caused by genetic disease. Almost 50 per cent of all miscarriages worldwide are due to chromosomally defective fetus.

Furthermore, according to the World Health Organization, over 10,000 human diseases are linked to single gene mutation alone. Among these monogenic diseases are thalassaemia, sickle cell anemia, haemophilia, Fragile-X syndrome, cystic fibrosis, and Huntingtons disease.

The other two major types of genetic disorders are chromosomal and complex disorder, where theres mutation in two or more genes.

Genetic disease is not also simply inherited, our environment is another factor that can trigger mutation. Cancer, diabetes, and heart disease are classified as multifactorial inheritance genetic disorders.

Considering all these, one would expect that the world will be welcoming the revolutionary gene therapy with wide-open arms.

Yet, UniQures Glybera has been recently withdrawn from the European market in spite of its promising one-time cure for lipoprotein lipase deficiency (LPLD).

LPLD is a rare genetic disorder characterized by the bodys lack of lipase, which is an enzyme that breaks down triglycerides from the blood. The deficiency results to recurrent abdominal pain, fat deposits in the skin (xanthomata), and repeated attacks of acute pancreatitis. LPLD is known to affect one person in a million. However, UniQures Glybera costs as much as $1 million per patient. Since the drugs introduction in 2012, only one patient has been subscribed to the treatment.

Another genetic drug that offers one-time cure for Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) is GlaxoSmithKlines Strimvelis. ADA-SCID is an inherited genetic condition characterized by a damaged immune system. People with SCID are prone to persistent and recurring infections since they absolutely have no immune protection from microbes. Symptoms begin to appear in a babys first 6 months of life, and afflicted infants hardly reach two years of age without treatment.

GlaxoSmithKlines Strimvelis can cure the genetic disease and save precious lifes. But the $700,000 drug had only a couple of sales in 2016 and another two expected this year. With this disappointing development, GSK might simply sell its rare diseases unit.

Data shows that the prices of the current gene therapy in the market are too hard if not impossible for most families to reach, especially since it has to be a one-time payment. And health care systems which only pay on monthly basis are not of much help to pharmaceuticals, which have made such enormous investments to formulate genetic cures.

Is there real hope?

Many drug companies still think so.

Pfizer, Sanofi, and Shire are now also making the revolutionary pursuits. And GSK has not completely given up as it strives to use its gene therapy platform in the development of cure for more common genetic illnesses.

Yes, at the moment, the whole picture may appear dim. But, by creating new business models, the leading companies in the biopharmaceutical industry if they are really serious about doing something in relation to rampant increases in drug prices, can start by creating a business model which is first based on humanism and then their respective bottom lines.

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Gene Therapy is Finally Here, But Who Will Foot the Bill - Wall Street Pit

LONDON, Aug 8 (Reuters) - Gene therapy, which aims to patch faulty genes with working DNA, has been a long time in development. The following are major milestones:

1972 - Researchers first suggest gene therapy as a treatment for genetic diseases but oppose its use in humans "for the foreseeable future", pending greater understanding of the technology.

1990 - A four-year-old girl with severe immunodeficiency became the first patient to undergo gene therapy in the United States.

1999 - American patient Jesse Gelsinger dies following a gene therapy experiment, setting the field back several years as U.S. regulators put some experiments on hold.

2002-03 - Cases of leukaemia are diagnosed in French children undergoing gene therapy in a further blow to the field.

2003 - The world's first gene therapy is approved in China for the treatment of head and neck cancer.

2007 - Doctors carry out the world's first operation using gene therapy to treat a serious sight disorder caused by a genetic defect.

2012 - Europe approves Glybera, the first gene therapy in a Western market, for an ultra-rare blood disorder.

2016 - Europe approves Strimvelis for a very rare type of immunodeficiency.

2017 or 2018 - The first gene therapy could be approved in United States. (Reporting by Ben Hirschler; editing by David Stamp)

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TIMELINE-Gene therapy's long road to market - Reuters - Reuters

Pharmaceutical giant Pfizer is expanding its facilities in Sanford to accommodate the companys push into gene therapy.

The state Department of Commerce announced earlier this week that Pfizer would invest $100 million in the site and create 40 jobs there within three years. The average annual salary for the new positions will be $97,500, much higher than Lee Countys average annual wage of $38,250.

If it meets those goals, Wyeth Holdings, a wholly owned subsidiary of Pfizers, will receive a $250,000 grant from the One North Carolina Fund and a local incentive of up to $1,412,715 over five years.

The announcement comes a week after Gov. Roy Cooper visited Pfizers facilities in Sanford and a year after Pfizer bought Bamboo Therapeutics, a Chapel Hill startup. Pfizer also bought Bamboos gene therapy manufacturing facility, which Bamboo had acquired from UNC-Chapel Hill in January, 2016.

Gene therapy is an emerging technology that attacks the disorder by repairing mutated genes. Pfizer will use technology to introduce genetic material into a patients body so as to compensate for defective or missing genes.

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Pfizer's push into gene therapy adds more jobs in Sanford - News & Observer

Researchers from the University of Chicago have successfully completed a proof-of-concept studywhere they managed to treat obesity in mice using a new type of gene therapy that utilized skin transplants. Human skin transplantation is a well-established clinical approach that has been used for the treatment of burns. However, using it as a vehicle to deliver genetic treatments for non-skin diseases could be revolutionary.

There are several reasons why skin stem cell therapy can be applicable to a broad type of diseases. The skin is the largest human organ, providing an easy access to cells needed for genetic treatments. The skin enables easy monitoring for potential off-target mutations resulting from the CRISPR intervention, as well as easy removal of such mutations, should they occur. Most importantly, proteins that are secreted by epidermal cells can reach the blood circulation and achieve desired therapeutic effects for the entire body.

In the study published this month, titledEngineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetes,the scientists genetically engineered skin cells to be able to deliver GLP1 (glucagon-like peptide 1) - a hormone which regulates blood glucose. Then they developed a surgical procedure which allowed them to successfully engraft the new skin onto a mouse host. Finally, the genetically modified cells had a mechanism for releasing GLP1, which was regulated by a small amount of antibiotic that was fed to the mice. The treated group of obese mice significantly reduced their body weight and insulin resistance, compared to the control group.

Xiaoyang Wu, one of the authors of the study, says in an interview for ResearchGate:

We established a novel mouse to mouse skin transplantation system to test skin gene therapy. [] Our proof-of-concept work demonstrated its possible to use engineered skin grafts to treat many non-skin diseases. Clinical translation of our findings will be relatively easy, as skin transplantation in human patients has been well established and clinically used for treatment of burn wounds for many years.

Skin grafts are an exciting new avenue to explore for genetic treatments of diseases. They are relatively inexpensive compared to other types of gene therapy, the procedure is minimally invasive, and it has already been tested and proven safe.

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A Novel Form of Gene Therapy Can Treat Diabetes With Genetically Modified Skin Transplants - Big Think

Pfizer is moving forward with plans to invest in a new clinical and commercial gene therapy manufacturing facility in Sanford, NC, but the work is still in the preliminary stages, said the company. A $100-million investment in the Sanford facilities is expected to create 40 jobs, according to a press release from the North Carolina governors office.

The facility will build upon a technology first developed at the University of North Carolina at Chapel Hill. Gene therapy focuses on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Gene therapy is an important area of focus for Pfizer. In 2016, the company acquired Bamboo Therapeutics, a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research, according to the press release.

A performance-based grant of $250,000 from the One North Carolina (NC) Fund will help facilitate Pfizers expansion. The One NC grant will formally be awarded to Wyeth Holdings, a wholly owned subsidiary of Pfizer. The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

Source: Pfizer, NC Governors Office

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Pfizer Plans Gene Therapy Manufacturing Investment in North ... - Pharmaceutical Technology Magazine

Regenxbio has joined forces with investment firm OrbiMed and a new nonprofit foundation to create Prevail Therapeutics, a startup focused on new biologics and gene therapiesfor Parkinson's disease (PD).

Prevail will draw on the expertise of the Silverstein Foundation for Parkinson's with GBA, which concentrates on a particular form of the disease caused by mutations in the glucocerebrosidase gene.

The foundation was set up this year by OrbiMed's co-head of private equity Jonathan Silverstein, who was diagnosed with GBA-linked PD in February and is mobilizing efforts to discover a cure for the disease. Silverstein backed the foundation with $10 million of his own money, and is intent on accelerating research into PD with GBA as well as other forms of the disease.

Prevail says it will focus initially on research coming out of the lab of its co-founder and CEO Asa Abeliovich, M.D., Ph.D., who is on the faculty of Columbia University as well as being a scientific adviser to the Silverstein Foundation and co-founder of neurodegenerative disease biotech Alector.

By joining forces with Regenxbio, Prevail launches with an exclusive license to the gene therapy specialist's adeno-associated virus (AAV) based vector technology NAV AAV9 for PD and other neurodegenerative disorders.

Silverstein said that the NAV platform and Dr. Abeliovich's "deep expertise in the molecular mechanisms of neurodegeneration provides us with a promising opportunity to develop potential life-changing therapies for patients suffering from Parkinson's disease and other neurodegenerative diseases."

He told CNBC today that Prevail's board will also have some big names, including Leonard Bell, co-founder and former CEO of Alexion, OrbiMed venture partner and Alexion co-founder Steve Squinto and serial entrepreneur Peter Thompson of Silverback Therapeutics and Corvus Pharmaceuticals.

The new company will initially focus on GBA1, the most common of the PD mutations, which is estimated to be present in up to 10% of U.S. PD patients and perhaps 100,000 people worldwide. The disease mechanism linked to the mutationan accumulation of alpha-synuclein in the brainmay have implications for the broader PD population and other neurodegenerative diseases.

"Many of the drugs we are trying for Parkinson's with GBA may work in the broader Parkinson's population," said Silverstein. The aim will be to get drugs approved for use in GBA patients first, and then expand their use into other patient groups.

The work of the foundation is attracting investment from companies who are not even active in PD, with cancer specialist Celgene today pledging a grant of $5 million.

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Silverstein-backed startup will test gene therapy for Parkinson's - FierceBiotech

A new consortium, led by Oxford BioMedica, will embark on a two-year, 2 million project focused on gene and cell therapy manufacturing.

Other partners include the Cell and Gene Therapy Catapult, Stratophase and Synthace, and the collaboration is co-funded by Innovate UK.

The aim of the consortium is to explore and apply novel advanced technologies to further evolve OXBs proprietary suspension LentiVector platform to deliver higher quality vectors for both clinical and commercial use. The project aims to deliver tangible benefits to patients by shortening the time-to-clinic and time-to-market as well as to improve the cost and access of bringing novel gene and cell therapies to patients.

Each partner in the collaboration holds proprietary technology and know-how that can be used to develop an innovative approach to viral vector manufacturing. The aims of this pioneering project are closely aligned with the current government national priorities to make the UK a global hub for manufacturing advanced therapies, which will benefit economic growth and create and retain more highly skilled employment.

John Dawson, CEO of Oxford BioMedica, commented: Cell and gene therapies offer unprecedented promise for the cure, treatment or long term management of disease and we are delighted that this consortium has been awarded funding from Innovate UK that will help to keep Oxford BioMedica, our partners and the UK at the forefront of innovation in industrial viral vector manufacturing."

Keith Thompson, CEO of Cell and Gene Therapy Catapult, added: Collaborating on developing improved process analytic technologies with our partners will help drive productivity in viral vector manufacturing, accelerating the development of these transformative advanced therapies. We have the opportunity to both transform patients lives and grow an industry in the UK that we can be proud of.

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2m UK consortium to tackle gene therapy - PharmaTimes

By Ben Hirschler

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Read more from the original source:
Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

LONDON (Reuters) - Gene therapy, which aims to patch faulty genes with working DNA, has been a long time in development. The following are major milestones:

1972 - Researchers first suggest gene therapy as a treatment for genetic diseases but oppose its use in humans "for the foreseeable future", pending greater understanding of the technology.

1990 - A four-year-old girl with severe immunodeficiency became the first patient to undergo gene therapy in the United States.

1999 - American patient Jesse Gelsinger dies following a gene therapy experiment, setting the field back several years as U.S. regulators put some experiments on hold.

2002-03 - Cases of leukaemia are diagnosed in French children undergoing gene therapy in a further blow to the field.

2003 - The world's first gene therapy is approved in China for the treatment of head and neck cancer.

2007 - Doctors carry out the world's first operation using gene therapy to treat a serious sight disorder caused by a genetic defect.

2012 - Europe approves Glybera, the first gene therapy in a Western market, for an ultra-rare blood disorder.

2016 - Europe approves Strimvelis for a very rare type of immunodeficiency.

2017 or 2018 - The first gene therapy could be approved in United States.

Reporting by Ben Hirschler; editing by David Stamp

Read more from the original source:
Timeline: Gene therapy's long road to market - Reuters

LONDON - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given the lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

READ:Researchers use gene editing on human embryo for first time in US

Glybera, costing around $1-million (R13-million) per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win US approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get the USgo-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Pay-for-performance

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centres in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400-million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1-million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

READ:20 years after cloning Dolly: Everything you always wanted to know

"In an area like haemophilia I think that approach is going to make a tonne of sense since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where speciality drug makers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1-billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Reuters

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Drugmakers' hopes for gene therapy rise despite tiny sales in Europe - eNCA

Updated Aug. 8, 2017 at 7:02 a.m.

Published: 2017-08-07 16:07:00 Updated: 2017-08-08 07:02:05

Sanford, N.C. Pharmaceutical giant Pfizer Inc. plans to invest $100 million in its Sanford operations as part of a push into gene therapy, officials said Monday.

The effort builds on a technology developed at the University of North Carolina at Chapel Hill and will create 40 jobs in Sanford.

"Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy," Lynn Bottone, site leader at Pfizer Sanford, said in a statement. "We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility."

Preliminary work on the expansion and initial hiring have already begun. The 230-acre campus employs about 450 people, reports the N.C. Biotechnology Center.

Gene therapy is a potentially transformational technology for patients that involves highly specialized, one-time treatments to address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Last year, Pfizer acquired Bamboo Therapeutics Inc., a privately held biotechnology company in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

"We are excited that Carolinas research will improve lives and create jobs for North Carolinians," UNC-Chapel Hill Chancellor Carol Folt said in a statement. "This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina, and we look forward to continue to help advance this industry."

Pfizer is also expanding a drug-manufacturing facility in Rocky Mount that it acquired from Hospira in 2015. The $190 million project will add 65,000 square feet of sterile injectable facilities but will not create any new jobs. The plant employs about 300 people.

Gov. Roy Cooper visited Pfizers Sanford facility last week to take a tour and meet with the companys senior leaders.

"North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line," Cooper said in a statement. "Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward."

Pfizer qualified for a performance-based grant of $250,000 from the One North Carolina Fund, which provides state assistance matched by local governments to help attract economic investment and create jobs. Companies receive no money upfront and must meet job and investment targets to obtain payment.

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Pfizer to invest $100M in Sanford gene therapy operation, add jobs ... - WRAL Tech Wire

Bluebird Bio plans to bring its gene therapies to market in Europe before the U.S., thanks to a favorable regulatory pathway.

Bluebird's head of Europe, Andrew Obenshain, told the Daily Telegraph that the company is already in negotiations with the EMA and the U.K.'s Medicine and Healthcare products Regulatory Agency (MHRA) on possible regulatory filings.

The EMA's adaptive pathways processwhich allows new therapies to be approved in stages based on stepwise collection of datais a key part of that decision, as is the fact that the agency "works very closely with companies coming forward with new methodologies," said Morgan. And with Brexit looming, it makes sense to discuss these plans with the MHRA separately.

Two years ago, Bluebirdwhich targets severe genetic diseases and cancerwas hit hard when the NorthStar trial of lead therapy LentiGlobin failed to hit the mark in sickle cell disease and beta thalassemia, mainly because of variable patient responses to the treatment.

In a recent SEC filing, the company said that combined data from Northstar and other trials, including a follow-up Northstar-2 study, "could support the filing of a marketing authorization application in the EU" for transfusion-dependent thalassemiaprovided they all meet the primary objective of freeing patients from the need for regular blood transfusions.

So far, no approved gene therapies have been in the U.S., while Europe has seen two approvals, namely for UniGene's Glybera (alipogene tiparvovec) for lipoprotein lipase deficiency and GlaxoSmithKline's Strimvelis for the ultrarare "bubble boy syndrome," or ADA-SCID.

Even getting approval is no guarantee of success, however. Glybera was taken off the market in April due to a lack of demand for the 1 million (around $1.2 million)-per-year therapy, with only one patient receiving it commercially since its launch in 2012.

GSK, meanwhile, has priced Strimvelis at a lower rate (around $650,000 a year) to try to encourage takeup, but hasn't given any updates and said last week it may put its rare disease unit up for sale. Rare disease head Carlo Russo moved to Italian biotech Genenta in January.

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Bluebird Bio sees Europe as first market for its gene therapies - FierceBiotech

A University of Chicago-based research team has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In a study inthe journal Cell Stem Cell, the researchers provide proof-of-concept. They describe gene-therapy administered through skin transplants to treat two related and extremely common human ailments: Type 2 diabetes and obesity.

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, said study author Xiaoyang Wu, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu said. It took us a few years to optimize our 3-D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. We have a better than 80 percent success rate with skin transplantation, Wu said. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid. Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors wrote.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu said. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.

There is also a need. More than 100 million U.S. adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study were Japing Yue, Queen Gou, and Cynthia Li from the University of Chicago and Barton Wicksteed from the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society and the V Foundation funded the study.

Article originally appeared on Science Life.

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Gene therapy via skin could treat diseases such as obesity - UChicago News

BioMarin Pharmaceutical on Monday dedicated its new Novato manufacturing facility which is expected to be key in its continuing clinical trials on a drug the company believes will potentially genetically repair the cause of hemophilia A.

Before a crowd of 300 to 400 people, the company, which manufactures drugs mostly for rare diseases, called its new production location the largest gene-therapy-manufacturing facility in the world. The project was completed 11 months ahead of schedule, employing 300 people in 200,000 construction hours, according to Robert Baffi, the firms executive vice president, Technical Operations.

Jean-Jacques Bienaim, chairman and CEO of BioMarin, said the drug to be produced at the location, BMN 270 gene therapy for hemophilia A, has the potential to change what future doctors learn about hemophilia.

Because of a genetic flaw, the blood of those who have hemophilia does not clot. The mutation takes places in a single gene that provides instructions to make a protein called Factor VIII, which is essential for blood to clot normally.

According to the company, the drug thus far in investigational clinical trials has shown the ability to genetically correct the problem and allow patients to manufacture and maintain a constant level of Factor VIII. Production of the drug to be used in those continuing trials will begin as soon as possible in Novato.

Among those affected by the hemophilia is the son of Christine Orr a speaker at todays event. Genetic roulette resulted in an older son being born without the problem.

But soon after her younger son was born, it became apparent he had little or no clotting factor. Every other day, home infusions of clotting factor have helped curb the problem, but she said her son experienced the stigma of parents being afraid to invite him to birthday parties or play dates over what might happen if he were to be hurt.

She said a one-shot treatment to potentially genetically treat and cure the disease gives her hope that yes, a cure is on my horizon, and he can choose his path in life and not have hemophilia choose it for him.

On Aug. 2, BioMarin Pharmaceutical reported it reaped $317 million in second-quarter revenue, up 6 percent from the same quarter in 2016.

It operated a loss of $37 million for the second quarter, but far less than the $419 million loss in the same quarter last year. The last quarters losses amounted to 21 cents per diluted share.

BioMarin, which has six main drugs on the market, had two huge contributors to second-quarter revenue: Kuvan, with $102 million, and Vimizim, with $103 million.

Kuvan, sapropterin dihydrochloride, treats a genetic disorder called phenylketonuria. BioMarin bought global rights to Kuvan in 2015 from Merck for 340 million euros, about $405 million. PKU is rare, and causes amino acid phenylalanine to build up in the body. The buildup of the amino acid can cause grave health problems.

Vimizim treats patients with mucopolysaccharidosis type IV-A, also called Morquio A syndrome, which is a metabolic disorder that inhibits the bodys ability to process certain mucopolysaccharides. It is usually inherited.

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BioMarin Pharmaceutical launches gene therapy drug plant in Novato - North Bay Business Journal

Agilis Biotherapeutics has formed a joint venture with Japans Gene Therapy Research Institution (GTRI). The alliance gives Agilis a base in Japan and a partnership with a fellow CNS specialist to support its development of adeno-associated virus (AAV) vectors and gene therapies.

Cambridge, Massachusetts-based Agilis set up the joint venture using a grant from the Japanese government. The agreement will establish an AAV manufacturing facility in Japan, from where Agilis and GTRI will work on vectors using Sf9 baculovirus and HEK293 mammalian cell systems. Agilis and GTRI plan to develop and manufacture AAV gene therapy vectors through the joint venture.

Agilis and GTRI also plan is to collaborate on the development and commercialization of certain CNS gene therapies.

GTRIs background suggests it is well-equipped to contribute to the project. The Japanese company grew out of the work of Shin-ichi Muramatsu, M.D., a scientist who sequenced AAV3 in the 1990s before going on to create AAVs designed to cross the blood-brain barrier. GTRI is working on gene therapies against diseases including Alzheimers, amyotrophic lateral sclerosis and Parkinsons that build on this research into AAVs.

Both biotechs are developing gene therapies to treat aromatic l-amino acid decarboxylase (AADC) deficiency. GTRI aims to get its candidate into the clinic in 2019. Agilispicked up its candidate from a university in Taiwan, which enrolled 18 patients in two clinical trials of the gene therapy. Those trials have taken the candidate toward a pivotal trial.

These programs may benefit from the joint venture. Working out of the Life Science Innovation Center of Kawasaki City, the joint venture intends to develop and produce AAVs for use in gene therapies against AADC deficiency and Parkinson's.

The joint venture marks the second time Agilis has looked outside of its walls for help with AAV vectors. Late in 2013, Agilis struck a deal with Intrexon that gave it access to the latters vector platform. Agilis is using the vectors to develop a treatment for Friedreichs ataxia.

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Agilis forms joint venture to advance gene therapy vectors - FierceBiotech

Researchers at the University of Missouri have developed a new method to efficiently deliver the correct form of dystrophin gene to muscles as a way to correct the faulty gene that characterizes Duchenne muscular dystrophy (DMD), a mouse study shows.

Their study, A Five-Repeat Micro-Dystrophin Gene Ameliorated Dystrophic Phenotype in the Severe DBA/2J-mdx Model of Duchenne Muscular Dystrophy, appearedin the journal Molecular TherapyMethods & Clinical Development.

DMD is caused by a modification of the gene that encodes the dystrophin protein, which is essential for normal muscle activity. Such mutations interfere withproduction of the functional protein, severely affecting muscle fiber structure and strength.

Correcting the faulty gene could potentially treatthis disease. Several attempts atgene therapyhave been tried, but all have failed to efficiently reverse all DMD symptoms.

Gene therapy commonly uses vectors basedviral genetic sequences to achieve the desired gene transfer capacity. The therapeutic potential of these techniques rely not only on the delivery system, but also on the sequence of the gene of interest that is used. In this case, smaller versions of dystrophin known asmicrodystrophinmust be used, since its natural form is just too big to be useful in gene therapy.

There have been other gene-transfer vectors attempted in the past (such as adenoviral vector, herpes simplex virus and plasmid), but they have largely been unsuccessful due to the complexity of the disease, challenges associated with delivery, and the large size of the native dystrophin gene, the studys senior author, Dongsheng Duan, said in a news release.

Duans team used an engineered form of the adeno-associated virus (AAV) vector to replace the damaged gene specifically in the muscles.

Researchers alsoused a version of the dystrophin gene that can potentiallyminimize the toxicity signs commonly associated with such methods, such as inadequate blood supply and fatigue during muscle contraction. This AAV viral vector has also been used in the past, but this is the first time researchers have combined it with such a version of dystrophin.

This strategy boostedlevels of dystrophin protein in the muscles of mice models of DMD, and significantly reduced some disease symptoms. Yet researchers could not accurately measure the impact of this new potential therapy to correct DMD-associated effects on the hearts of the animals.

Human studies have shown that one-time intramuscular injection of an AAV vector can result in the expression of a therapeutic protein for many years. For example, a study showed Factor IX expression for 10 years in a hemophilia patient, Duan said. In preclinical studies in murine and canine models, we have also observed persistent multiyear microdystrophin expression from AAV vectors. In the case of mice, a single injection can lead to microdystrophin expression throughout the lifespan.

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DMD Gene Therapy to Fix Dystrophin Deficiency in Mice Shows ... - Muscular Dystrophy News

With its lead gene therapy under FDA review, Spark Therapeutics $ONCE is now unveiling the first encouraging responses on the hemophilia A front.

Jeffrey Marrazzo

With analysts looking for a 12%-plus Factor VIII response, the company says that investigators tracked an 11% and 14% stabilized rise in Factor VIII activity in the first two patients who were given the therapy in the dose-escalation study.

Key to this part of the process, researchers say they have seen no Factor VIII inhibitors appear, no thrombotic events, no spontaneous bleeds and no need to use corticosteroids on the patients, who have been tracked for 23 and 12 weeks.

As a result, the biotech says that it has now doubled the dose and treated the third patient in the proof-of-concept study. States the company: While the results for this third participant are early, his factor activity level is tracking proportionally higher, consistent with the dose escalation.

Spark shares surged 15% this morning as the biotech updated the data as well as its Q2 results.

Noted Jefferies Michael Yee recently: First data from Phase I/II of Hemophilia A gene therapy SPK-8011 in July/Aug could establish early proof-of-concept and be a (+) catalyst. Given small no. of pts to start, key is demonstrating potential to get to 12%+ Factor VIII.

Spark Therapeutics is the most advanced biotech in the US gene therapy field, with a good chance to win the first ever FDA approval for a once-and-done treatment. As a result, analysts are watching every step CEO Jeff Marrazzo makes. The biotech has been making steady progress with a gene therapy for hemophilia B after getting over some early safety jitters. And just days ago Spark was handed a priority review of its lead program forRPE65-mediated inherited retinal disease, putting it first in line for a US approval.

To be sure, Spark isnt alone in hemophilia A. Sangamo has a program underway. But the leader in this field is BioMarin $BMRN, which has produced some stellar though also puzzling results. Now ready to go into Phase III, early-stage studies demonstrateda wide variability in Factor VIII expression needed to keep hemophilia in check. Joseph Schwartz at Leerink has noted that investors will look closely to see if regulators are concerned by the much-higher-than-normal levels of Factor VIII in some patients before approving the Phase III design. In the meantime, look for some careful examination of stability versus high but variable impact.

Once over the finish line, gene therapies will present payers with a thorny issue. How do you cover therapies that have the promise of being used just once, without any guarantees that they can last a lifetime? Prices are expected to be sky high, which has held back the two gene therapies that have been approved in Europe, though only rarely used.

Katherine High

The encouraging start of our SPK-8011 clinical trial reinforces the strength of our gene therapy platform, delivers human proof-of-concept in a second liver-mediated disease a significant achievement in the gene therapy field and positions us well to potentially transform the current treatment approach for this life-altering disease with a one-time intervention, said Katherine High, president and chief scientific officer of Spark Therapeutics. We are excited about the progress we are making to achieve our goals of our investigational hemophilia A and B programs: to safely achieve predictable, consistent and sustained activity levels that prevent spontaneous bleeding.

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Spark Therapeutics offers a glimpse of efficacy in first two hemophilia A gene therapy patients - Endpoints News

Dive Brief:

Even as gene therapies are being touted as the next wave of innovation that could offer cures for certain genetic conditions, it remains to be seen whether these products are actually commercially viable. There has yet to be a gene therapy approved in the U.S. (although Spark Therapeutics' application is pending), but two of the transformative drugs have been on the market in Europe.

Yet neither of those commercially available gene therapies have found much success. GlaxoSmithKline plc. said just last week it is looking to move away from its rare disease portfolio, including the gene therapy Strimvelis. Meanwhile, uniQureannounced back in April it would not renew the marketing authorization application in Europe for its already-approved gene therapy Glybera.

This latest move by Chiesifurther exemplifies the challenges gene therapy producers face. The announcement ends a deal which has been in place since 2013. Chiesisaid in a statement that the decision was "driven by recent changes in our strategic priorities."

uniQuretried to put brave face on the news, but partnership exits are rarely good news for a biotech.

"By regaining unencumbered, global rights to a late-stage program that has demonstrated significant clinical benefit for patients with hemophilia B, we believe uniQure is better positioned to accelerate the global clinical development plan, maximize shareholder return on our pipeline and take advantage of new potential opportunities related to the program," said CEO Matthew Kapusta.

The company recently announced positive developments in a Phase 1/2 trial of AMT-060, which supported further expansion of the eligibility of the adeno-associated virus 5 (AAV5) gene therapy to nearly all patients with hemophilia B. Meanwhile, investors are paying close attention to Spark's gene therapy for hemophilia B, which is also in early-to mid-stage development.

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Chiesi hands back gene therapy to uniQure | BioPharma Dive - BioPharma Dive

A rose will bloom, it then will fade. Alas, not so for those afflicted with Hutchison-Gilford Progeria Syndrome (HGPS). Their lives skip the blooming stage. Within a few months of birth their growth is stunted and they begin to show the hallmarks of ageing. Their skin loses its elasticity and their hair falls out. As teenagers they resemble tiny, gnomish octogenarians, with prominent eyes, pinched noses, receding jaws and veins protruding through thin transparent skin. The average age of death is 13 usually from a heart attack or stroke.

Cardiologist John Cooke is trying to help those with the disease by at least slowing the ageing and stiffening of their blood vessels. His approach involves rejuvenating this tissue by delivering transient gene therapy using messenger RNA for a gene called telomerase. Since messenger RNA does not hang around, the technique avoids the pitfalls of gene therapy, like inadvertently triggering cancer.

The results of his research, published this week in the Journal of the American College of Cardiology, show the successful rejuvenation of cells in the test tube from youngsters with HGPS.

It brings tears to my eyes to see these kids but despite the fact theyre trapped in the body of an 80-year-old, he says. Theyre not bitter. They are intelligent and hopeful. They want to count the stars.

The efforts of Cooke and colleagues based at the Houston Methodist Research Institute in Texas wont just benefit children with progeria; there are potential pluses for most of us who are also likely to die of heart disease.

The cells of those afflicted with HGPS have a shortened life span. Compared to normal cells, they multiply fewer times before becoming senescent cells that are no longer able to rejuvenate through dividing. The fault lies with the worn-down tips of their chromosomes, known as telomeres. In normal cells, the telomeres are much longer.

This is all a consequence of the LMNA mutation that is the underlying cause of HGPS. It impairs the way DNA is housed in the nucleus, buckling the appearance of the nucleus and also meaning the DNA cannot be properly maintained particularly the vulnerable ends, which fray. Cells with seriously frayed telomeres become senescent. They no longer divide or respond to the environment in a normal way, and ooze inflammatory factors. In the case of the endothelial cells that line the blood vessels, Cooke says, this means they dont line up against the shear stress and they become stickier, attracting plaque.

For several years Cooke has wondered whether it might be possible to restore ageing endothelial cells to a more youthful state by repairing the telomere ends not just in youngsters with HGPS but everybody.

The enzyme telomerase is designed to do this job; but delivering a hard copy of the gene to the cells is probably a bad idea: cancer cells often rely on activating telomerase.

So Cooke opted for giving the cells a soft copy the messenger RNA that carries the same information as the gene but doesnt hang around. It is sort of like a flimsy photocopy of an important manuscript.

The just-published study was a proof of concept. The Houston researchers took skin cells from 17 youngsters with HGPS aged one to 14 and grew out cells called fibroblasts. (Its much harder to extract endothelial cells that line the blood vessels). In 12 of the patients, the fibroblasts showed abnormally short telomeres. Five of the younger patients (aged eight years or less) had normal length telomeres something that surprised the researchers. When the scientists added the messenger RNA of the telomerase gene, the cells with short telomeres kicked back into replicating again. On the other hand, the cells that had normal length telomeres showed no response.

The study suggests that the delivery of the telomerase messenger RNA is able to rejuvenate fibroblast cells. It presumably might do the same for the endothelial cells and blood vessels of youngsters with HGPS. The next step, Cooke says, is to work on techniques to deliver the telomerase messenger RNA into the body, perhaps using nanoparticles.

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Transient gene therapy may help youngsters with a premature ... - Cosmos

LONDON (Reuters) - GlaxoSmithKline is swimming against the tide by getting out of treatments for rare diseases at a time when rivals like Sanofi and Shire see the field as a rich seam for profits.

Successful medicines for rare conditions are potentially very lucrative, since prices frequently run into hundreds of thousands of dollars, but patient numbers can be extremely low.

New GSK Chief Executive Emma Walmsley announced the strategic review and potential divestment of rare diseases on Wednesday as part of a wide-ranging drive to streamline pharmaceutical operations.

It follows a less than impressive experience for GSK in the field, including the fact that its pioneering gene therapy Strimvelis only secured its first commercial patient in March, 10 months after it was approved for sale in Europe in May 2016.

Since then a second patient has also been treated and two more are lined up to receive the therapy commercially, a spokesman said.

Strimvelis, which GSK developed with Italian scientists, is designed for a tiny number of children with ADA Severe Combined Immune Deficiency (ADA-SCID). SCID is sometimes known as "bubble baby" disease, since those born with it have immune systems so weak they must live in germ-free environments.

The new treatment became the first life-saving gene therapy for children when it was approved last year, marking a step forward for the emerging technology to fix faulty genes.

Walmsley said GSK was not giving up on gene and cell therapy entirely. Research will be focused in future in areas with larger potential patient numbers, including oncology.

Reporting by Ben Hirschler; Editing by Adrian Croft

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GSK gives up on rare diseases as gene therapy gets two customers - Reuters