Category Archives: Gene therapy

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy to Abeona Therapeutics EB-101 gene therapy for epidermolysis bullosa (EB).EB patients have extremely delicate skin, often referred to as butterfly skin, because it becomes fragile like the wings of a butterfly and can fall apart at the touch.The disorder makes patients susceptible to blisters and poor healing of wounds. Recessive dystrophic epidermolysis bullosais the most severe form of the condition, and is the result of a mutation in COL7A1 gene, which encodes for collagen VII. Abeonas EB-101 is a skin graft that includes a healthy COL7A1 gene.

Breakthrough Therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions and it was granted based on data from the Phase 1/2 clinical trial showing significant wound healing (greater than 50% healed) over a 2-year period.

The EB-101 program has already been granted Orphan Drug and Rare Pediatric Disease Designations from the FDA and Orphan Drug Designation from theEuropean Medicines Agency(EMA).

EB-101 is an autologous gene-corrected cell therapeutic approach that utilizes a patients own cells and genetically engineering them to produce the correct version of collagen, which helps hold skin on to the body, thereby reducing the number of painful blisters caused by injury and improving wound healing, stated Timothy J. Miller, Ph.D., Abeonas President and CEO. We are grateful that the FDA has recognized the promising clinical data from the EB-101 program with Breakthrough Therapy designation and look forward to initiating our pivotal Phase 3 trial as we advance EB-101 for patients with this debilitating disease.

In May of this year, data from the Phase 1/2 trial were presented at the Society of Investigative Dermatology (SID) conference by Stanford collaborators, and demonstrated that EB-101 treated wounds were significantly healed >50% for more than two years post-administration. The data included:

An example of wound healing that occurred using the gene therapy is shown below.

Look for out exclusive interview with Dr. Miller later this week when we talk to him about EB-101 and the companys other gene therapies.

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Abeona Gene Therapy for Epidermolysis Bullosa Continues to Impress the FDA - Rare Disease Report

Federal regulators green-lighted an historic gene therapy Wednesday that uses the bodys own immune cells to attack an acute form of leukemia in children and young adults.

The Food and Drug Administration approved Kymriah to treat patients up to age 25 who suffer from ALL, a quick-acting cancer in the bone marrow and blood.

The pioneering treatment collects white blood cells known as T-cells from individual patients, genetically modifies them in the lab and reintroduces them in the patient to attack and kill leukemia cells.

Were entering a new frontier in medical innovation with the ability to reprogram a patients own cells to attack a deadly cancer, FDA Commissioner Scott Gottlieb said. New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.

The treatment developed by Novartis Pharmaceuticals Corp. is approved for patients up to age 20 with ALL, which is the most common type of childhood cancer in the U.S.

Roughly 3,100 patients are diagnosed per year.

The FDA warned that Kymriah could have severe side effects, including neurological problems, high blood pressure, kidney problems and fever. Because of the risks, the government says hospitals and clinics that dispense the drug must be specially certified.

Also, the FDA said Novartis is required to study the effects of its drugs on patients treated with its product.

Link:
FDA approves first-ever gene therapy in US - Washington Times

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 ... - Big Think

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."

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Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

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

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

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

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Timeline: Gene therapy's long road to market - Reuters