Category Archives: Gene therapy

The European Medicines Agency has validated BioMarins application to market its investigational AAV gene therapy, valoctocogene roxaparvovec, for adults with hemophilia A.

As such, the company said it expects the agencys review of the therapy in January next year under accelerated assessment.

The EMA granted access to its Priority Medicines (PRIME) regulatory initiative in 2017 for valoctocogene roxaparvovec and recently granted BioMarin's request for accelerated assessment of the MAA, potentially shortening the review period.

The submission is based on an interim analysis of study participants treated in an ongoing Phase III study with material from the to-be-commercialised process and updated three-year Phase I/II data.

It marks the first marketing application to be filed in Europe for a gene therapy product for any type of hemophilia.

BioMarin also announced the filing of a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for the treatment, with the review expected to being in February.

"We are pleased that the agency has recognised the potential scientific advancement that valoctocogene roxaparvovec could bring to people with severe hemophilia A," said Hank Fuchs, president, Global Research and Development at BioMarin.

"We continue to move thoughtfully and urgently through the regulatory review process to deliver a treatment that we believe has the potential to make a meaningful difference to people with hemophilia A.

Continued here:
BioMarin's haemophilia gene therapy moves forward in the EU - PharmaTimes

XconomyBoston

Ring Therapeutics, a Flagship Pioneering spinout, launched Thursday with ambitious plans to expand the universe of vectors available for gene therapy delivery.

Gene therapy, treatments intended to treat disease by inserting a gene instead of using drugs or surgery, has had a banner year, with the second ever such therapy approved this year in the US.

Ring want to use itsresearch into viruses that exist in the human body without apparent negative effects to provide more and better options to fuel the rise of gene therapy treatments.

For the past two years, Flagship Pioneering partner and Rings founding CEO Avak Kahvejian says the company has been exploring the human commensal viromebasically, a group of viruses that exist within humans without negative effectsfor its potential to address limitations of the vectors currently used.

The sector relies heavily on adeno-associated viruses (AAVs), which naturally infect humans but arent known to cause disease, to deliver the DNA. Previous exposure, however, can spark an immune response.

A lot of the workhouses in gene therapy have either been pathogenic viruses or viruses that have been taken from other species or viruses that are highly immunogenic, or all of the above, Kahvejian tells Xconomy. That leads to a certain number of limitations, despite the successes and advances weve made to date.

A number of issues stymie widespread use of AAVs, Kahvejian says, including the fact that 10 percent to 20 percent of people have at one time or another been infected with such a virus, thereby building up an immune response to it. Another concern is where such gene therapies end up, because viruses tend to gravitate toward certain types of tissues, and to go elsewhere, require special tweaking.

The Cambridge, MA-based startup believes the viruses it has found are unlikely to cause an immune response or prove pathogenic, given their ubiquity in the body.

Like extrachromosomal DNAa new discovery at least one company is exploring for its potential as a target in cancer treatmentsthe viral sequencing Ring is studying are circular pieces of DNA that exist outside the 23 chromosomes of the human genome.

Ring says it has found thousands of these viruses that coexist with our immune system. It aims to use those to develop vectors that can facilitate gene replacement throughout the bodymultiple times, if necessary. While gene therapy is thought of as a one-time fix, cell turnover means whatever the fix engendered by the inserted gene could falter over time, necessitating a re-up.

Kahvejian wouldnt share a timeline for Rings plan to develop re-dosable, tissue-targeted treatments.

Were looking at the unique features and activities of these viruses in different tissues to establish the various vectors were going to pursue, he said.

Flagship, which pursues scientific questions in-house and builds and funds companies around the answershas put $50 million toward Ring, which has about 30 employees.

Rings president is Rahul Singhvi, an operating partner at Flagship. Most recently he was chief operating officer of Takedas global vaccine business unit. Its head of R&D is Roger Hajjar, who has led gene therapy trials in patients with heart failure.

Ring is the second startup Flagship has spun out this month. Cellarity launched last week.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

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Ring Therapeutics Launches to Expand Gene Therapy Viral Vector Options - Xconomy

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States. Meredith Rizzo/NPR hide caption

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States.

When Victoria Gray was just 3 months old, her family discovered something was terribly wrong.

"My grandma was giving me a bath, and I was crying. So they took me to the emergency room to get me checked out," Gray says. "That's when they found out that I was having my first crisis."

It was Gray's first sickle cell crisis. These episodes are one of the worst things about sickle cell disease, a common and often devastating genetic blood disorder. People with the condition regularly suffer sudden, excruciating bouts of pain.

"Sometimes it feels like lightning strikes in my chest and real sharp pains all over. And it's a deep pain. I can't touch it and make it better," says Gray. "Sometimes, I will be just balled up and crying, not able to do anything for myself.

Gray is now 34 and lives in Forest, Miss. She volunteered to become the first patient in the United States with a genetic disease to get treated with the revolutionary gene-editing technique known as CRISPR.

NPR got exclusive access to chronicle Gray's journey through this medical experiment, which is being watched closely for some of the first hints that changing a person's genes with CRISPR could provide a powerful new way to treat many diseases.

"This is both enormously exciting for sickle cell disease and for all those other conditions that are next in line," says Dr. Francis Collins, director of the National Institutes of Health.

"To be able to take this new technology and give people a chance for a new life is a dream come true," Collins says. "And here we are."

Doctors removed bone marrow cells from Gray's body, edited a gene inside them with CRISPR and infused the modified cells back into her system this summer. And it appears the cells are doing what scientists hoped producing a protein that could alleviate the worst complications of sickle cell.

"We are very, very excited," says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., who is treating Gray.

Frangoul and others stress that it's far too soon to reach any definitive conclusions. Gray and many other patients will have to be treated and followed for much longer to know whether the gene-edited cells are helping.

"We have to be cautious. It's too early to celebrate," Frangoul says. "But we are very encouraged so far."

Collins agrees.

"That first person is an absolute groundbreaker. She's out on the frontier," Collins says. "Victoria deserves a lot of credit for her courage in being that person. All of us are watching with great anticipation."

This is the story of Gray's journey through the landmark attempt to use the most sophisticated genetic technology in what could be the dawn of a new era in medicine.

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe. Meredith Rizzo/NPR hide caption

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe.

Life filled with pain

When I first meet her, Gray is in a bed at the TriStar Centennial Medical Center in Nashville wearing a hospital gown, big gold hoop hearings and her signature glittery eye shadow.

It's July 22, 2019, and Gray has been in the hospital for almost two months. She is still recovering from the procedure, parts of which were grueling.

Nevertheless, Gray sits up as visitors enter her room.

"Nice to meet y'all," she says.

Gray is just days away from her birthday, which she'll be celebrating far from her husband, her four children and the rest of her family. Only her father is with her in Nashville.

"It's the right time to get healed," says Gray.

Gray describes what life has been like with sickle cell, which afflicts millions of people around the world, including about 100,000 in the United States. Many are African American.

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company. Meredith Rizzo/NPR hide caption

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company.

"It's horrible," Gray says. "When you can't walk or, you know, lift up a spoon to feed yourself, it gets real hard."

The disease is caused by a genetic defect that turns healthy, plump and pliable red blood cells into deformed, sickle-shaped cells. The defective cells don't carry oxygen well, are hard and sticky and tend to clog up the bloodstream. The blockages and lack of oxygen wreak havoc in the body, damaging vital organs and other parts of the body.

Growing up, Victoria never got to play like other kids. Her sickle cells made her weak and prone to infections. She spent a lot of time in the hospital, recovering, getting blood transfusions all the while trying to keep up with school.

"I didn't feel normal. I couldn't do the regular things that every other kid could do. So I had to be labeled as the sick one."

Gray made it to college. But she eventually had to drop out and give up her dream of becoming a nurse. She got a job selling makeup instead but had to quit that too.

The sickle-shaped cells eventually damaged Gray's heart and other parts of her body. Gray knows that many patients with sickle cell don't live beyond middle age.

"It's horrible knowing that I could have a stroke or a heart attack at any time because I have these cells in me that are misshapen," she says. "Who wouldn't worry?"

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says. Meredith Rizzo/NPR hide caption

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says.

Gray married and had children. But she hasn't been able to do a lot of things most parents can, like jump on a trampoline or take her kids to sporting events. She has often had to leave them in the middle of the night to rush to the hospital for help.

"It's scary. And it affected my oldest son, you know, because he's older. So he understands. He started acting out in school. And his teacher told me, 'I believe Jemarius is acting out because he really believes you're going to die,' " Gray says, choking back tears.

Some patients can get help from drugs, and some undergo bone marrow transplants. But that procedure is risky; there's no cure for most patients.

"It was just my religion that kind of kept me going," Gray says.

An eager volunteer

Gray had been exploring the possibility of getting a bone marrow transplant when Frangoul told her about a plan to study gene editing with CRISPR to try to treat sickle cell for the first time. She jumped at the chance to volunteer.

"I was excited," Gray says.

CRISPR enables scientists to edit genes much more easily than ever before. Doctors hope it will give them a powerful new way to fight cancer, AIDS, heart disease and a long list of genetic afflictions.

"CRISPR technology has a lot of potential use in the future," Frangoul says.

To try to treat Gray's sickle cell, doctors started by removing bone marrow cells from her blood last spring.

Next, scientists used CRISPR to edit a gene in the cells to turn on the production of fetal hemoglobin. It's a protein that fetuses make in the womb to get oxygen from their mothers' blood.

"Once a baby is born, a switch will flip on. It's a gene that tells the ... bone marrow cells that produce red cells to stop making fetal hemoglobin," says Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's TriStar Centennial Medical Center.

The hope is that restoring production of fetal hemoglobin will compensate for the defective adult-hemoglobin sickle cells that patients produce.

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain. Ed Reschke/Getty Images hide caption

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain.

"We are trying to introduce enough ... fetal hemoglobin into the red blood cell to make the red blood cell go back to being happy and squishy and not sticky and hard, so it can go deliver oxygen where it's supposed to," Frangoul says.

Then on July 2, after extracting Gray's cells and sending them to a lab to get edited, Frangoul infused more than 2 billion of the edited cells into her body.

"They had the cells in a big syringe. And when it went in, my heart rate shot up real high. And it kind of made it hard to breath," Gray says. "So that was a little scary, tough moment for me."

After that moment passed, Gray says, she cried. But her tears were "happy tears," she adds.

"It was amazing and just kind of overwhelming," she says, "after all that I had went through, to finally get what I came for."

The cells won't cure sickle cell. But the hope is that the fetal hemoglobin will prevent many of the disease's complications.

"This opens the door for many patients to potentially be treated and to have their disease modified to become mild," Frangoul says.

The procedure was not easy. It involved going through many of the same steps as a standard bone marrow transplant, including getting chemotherapy to make room in the bone marrow for the gene-edited cells. The chemotherapy left Gray weak and struggling with complications, including painful mouth sores that made it difficult to eat and drink.

But Gray says the ordeal will have been worth it if the treatment works.

She calls her new gene-edited cells her "supercells."

"They gotta be super to do great things in my body and to help me be better and help me have more time with my kids and my family," she says.

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer. Meredith Rizzo/NPR hide caption

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer.

Concerns about risk

Other doctors and scientists are excited about the research. But they're cautious too.

"This is an exciting moment in medicine," says Laurie Zoloth, a bioethicist at the University of Chicago. "Everyone agrees with that. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases."

Still, Zoloth worries that the latest wave of genetic studies, including the CRISPR sickle cell study, may not have gotten enough scrutiny by objective experts.

"This a brand-new technology. It seems to work really well in animals and really well in culture dishes," she says. "It's completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker."

Zoloth is especially concerned because the research involves African Americans, who have been mistreated in past medical studies.

Frangoul acknowledges that there are risks with experimental treatments. But he says the research is going very slowly with close oversight by the Food and Drug Administration and others.

"We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy," Frangoul says.

Gray says she understands the risks of being the first patient and that the study could be just a first step that benefits only other patients, years from now. But she can't help but hope it works for her.

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville. Meredith Rizzo/NPR hide caption

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville.

She imagines a day when she may "wake up and not be in pain" and "be tired because I've done something not just tired for no reason." Perhaps she could play more with her kids, she says, and look forward to watching them grow up.

"That means the world to me," Gray says.

It could be many weeks or even months before the first clues emerge about whether the edited cells are safe and might be working.

"This gives me hope if it gives me nothing else," she says in July.

Heading home at last

About two months later, Gray has recovered enough to leave the hospital. She has been living in a nearby apartment for several weeks.

Enough time has passed since Gray received the cells for any concerns about immediate side effects from the cells to have largely passed. And her gene-edited cells have started working well enough for her immune system to have resumed functioning.

So Gray is packing. She will finally go home to see her children in Mississippi for the first time in months. Gray's husband is there to drive her home.

"I'm excited," she says. "I know it's going to be emotional for me. I miss the hugs and the kisses and just everything."

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss. Meredith Rizzo/NPR hide caption

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss.

Gray is wearing bright red glittery eye shadow. It matches her red tank top, which repeats "I am important" across the front.

She unzips a suitcase and starts pulling clothes from the closet.

"My goodness. Did I really bring all this?" she says with a laugh.

Before Gray can finish packing and depart, she has to stop by the hospital again.

"Are you excited about seeing the kids?" Frangoul says as he greets her. "Are they going to have a big welcome sign for you in Mississippi?"

Turns out that Gray has decided to make her homecoming a surprise.

"I'm just going to show up tomorrow. Like, 'Mama's home,' " she says, and laughs.

After examining Gray, Frangoul tells her that she will need to come back to Nashville once a month for checkups and blood tests to see if her genetically modified cells are producing fetal hemoglobin and giving her healthier red blood cells.

"We are very hopeful that this will work for Victoria, but we don't know that yet," Frangoul says.

Gray will also keep detailed diaries about her health, including how much pain she's experiencing, how much pain medication she needs and whether she needs any blood transfusions.

"Victoria is a pioneer in this. And we are very excited. This is a big moment for Victoria and for this pivotal trial," Frangoul says. "If we can show that this therapy is safe and effective, it can potentially change the lives of many patients."

Gray hopes so too.

Originally posted here:
Sickle Cell Therapy With CRISPR Gene Editing Shows Promise : Shots - Health News - NPR

Man who implanted chips in his hand.

Paving the way for solving a major safety issue associated with gene therapies, scientists have developed a special molecular switch that could be embedded into such therapies to allow doctors to control dosing. The feat, published in the journal Nature Biotechnology, offers gene therapy designers what may be the first viable technique for adjusting the activity levels of their therapeutic genes.

The lack of such a basic safety feature has helped limit the development of gene therapy, which otherwise holds promise for addressing genetically based conditions.

"I think that our approach offers the only practical way at present to regulate the dose of a gene therapy in an animal or a human," said lead researcher Michael Farzan from the Scripps Research Institute in Jupiter in Florida, US.

Gene therapies work by inserting copies of a therapeutic gene into the cells of a patient, if, for example, the patient was born without functional copies of the needed gene.

The strategy has long been seen as having enormous potential to cure diseases caused by defective genes.

It could also enable the steady, long-term delivery to patients of therapeutic molecules that are impractical to deliver in pills or injections because they don't survive for long in the body.

However, gene therapies have been viewed as inherently risky because once they are delivered to a patient's cells, they cannot be switched off or modulated.

As a result, only a handful of gene therapies have been approved to date.

In this study, the researchers demonstrated the power of their new switching technique by incorporating it into a gene therapy that produces the hormone erythropoietin, used as a treatment for anaemia.

They showed that they could suppress expression of its gene to very low levels with a special embedded molecule, and could then increase the gene's expression, over a wide dynamic range, using injected control molecules called morpholinos that the US Food and Drug Administration has found to be safe for other applications.

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New 'molecular switch' allows control of gene therapy doses - International Business Times, Singapore Edition

I want to congratulate our team for their success in developing SB-525 through to this important milestone where we have handed over the IND to Pfizer for Phase 3 development, said Sandy Macrae, CEO of Sangamo. We are thrilled to be in a partnership where both parties have cooperated to accelerate study timelines, resulting in completion of the IND transfer ahead of schedule. Pfizer and Sangamo are united in our common interest to help patients with Hemophilia A and will do everything that we can to safely and expeditiously advance this promising gene therapy candidate for patients in need.

The SB-525 collaboration was established in May 2017. Under the terms of the collaboration agreement, Sangamo has been responsible for Phase 1/2 clinical development. Pfizer will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for SB-525. Sangamo is eligible to receive total potential milestone payments of up to $300 million for the development and commercialization of SB-525, and up to $175 million for additional Hemophilia A gene therapy product candidates that may be developed under the collaboration. Sangamo will, additionally, receive tiered royalties starting in the low teens and up to 20% of annual net sales of SB-525.

About Sangamo Therapeutics

Sangamo Therapeutics is committed to translating ground-breaking science into genomic medicines with the potential to transform patients lives using gene therapy, ex vivo gene-edited cell therapy, and in vivo genome editing and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Sangamo Forward Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of United States securities law. These forward-looking statements include, but are not limited to, the therapeutic potential of SB-525; the enrollment of clinical trials and global registration and commercialization and the expected timing for milestones the expected benefits of Sangamos collaboration with Pfizer; the anticipated capabilities of Sangamos technologies; and other statements that are not historical fact. These statements are based upon Sangamos current expectations and speak only as of the date hereof. Sangamos actual results may differ materially and adversely from those expressed in any forward-looking statements. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to dependence on the success of clinical trials; the uncertain regulatory approval process; the costly research and development process, including the uncertain timing of clinical trials; whether interim, preliminary or initial data from ongoing clinical trials will be representative of the final results from such clinical trials; whether the final results from ongoing clinical trials will validate and support the safety and efficacy of product candidates; the risk that clinical trial data are subject to differing interpretations by regulatory authorities; the potential inability of Sangamo and its partners to advance product candidates into registrational studies; Sangamos reliance on itself, partners and other third-parties to meet clinical and manufacturing obligations; Sangamos ability to maintain strategic partnerships; competing drugs and product candidates that may be superior to Sangamos product candidates; and the potential for technological developments by Sangamo's competitors that will obviate Sangamo's gene therapy technology. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamos operations. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission on March 1, 2019 and Sangamo's Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 that it filed on or about November 6, 2019. Except as required by law, we assume no obligation, and we disclaim any intent, to update these statements to reflect actual results.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191223005185/en/

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Sangamo Announces Early Completion of Transfer to Pfizer of SB-525 Hemophilia A Gene Therapy IND and an Earned $25 Million Milestone Payment -...

Sanofi was locked in a bidding war right up to the final moments of closing its $2.5 billion buyout of Synthorx, as it rushed to complete a deal this or another to bolster CEO Paul Hudsons new R&D vision before wrapping the year. By Synthorxs account, what began as routine partnership talks took a sharp turn into two weeks of intense negotiations in which the San Diego biotech was able to almost double the offer.

By moving swiftly and aggressively, Sanofi fended off three other suitors to pocket a slate of next-gen IL-2 drugs for cancer and autoimmune diseases as well as a synthetic biology platform. The pharma giant now takes over a pipeline whose most advanced asset it still in Phase I/II befitting an organization that now vows to get in early enough to change a treatment paradigm.

The initial meetings with Synthorx took place at all the usual places: ESMO 2018, JP Morgan and AACR 2019. Soon Sanofi R&D chief John Reed stepped in, but the smaller player continued to explore options with other companies at ASCO and BIO over the summer.

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UPDATED: Sarepta cements its DMD throne with $1B+ gene therapy deal with mighty Roche - Endpoints News

Gene therapy is providing unprecedented hope for growing numbers of patients and families. This game changer in medicine restores vision in babies born with congenital blindness, reconstitutes defences against infection in inherited immunodeficiencies and offers the perspective of curing the devastating neuromuscular disease, spinal muscular atrophy.

Gene therapy is also removing the need for repeat blood transfusions in adolescents with the inherited blood disorder, beta-thalassemia. Meanwhile, in oncology, CAR-T therapies, involving genetic modifications of a patients own immune cells, are proving life-saving for children or adults with certain types of blood cancers.

All these revolutionary treatments are now approved by regulatory agencies in Europe or the US. Unfortunately, they carry astronomical price tags which prevent their effective delivery to patients. As one case in point, Bluebird Bios Zynteglo for treating beta-thalassemia, has a list price of 1.57 million.

Can high prices be justified?

Gene therapy manufacturers defend their prices by pointing to high development and manufacturing costs, small markets, and unique therapeutic effectiveness as compared to the current standard of care. However, R&D costs are kept secret, and higher numbers of patients eligible for a given therapy do not translate into lower prices.

Indeed, several arguments the manufacturers put forward are dubious or even far-fetched. As of today, claims that a single administration of a gene therapy product will ensure a lifelong cure are simply not supported by the scientific evidence.

Likewise, value-based pricing is often misconceived. As stated by the US Institute for Clinical and Economic Review in its 2017 white paper on gene therapy, the established value of a treatment reflects the maximum price society might be prepared to pay for it - but should not dictate the price that is actually paid. In an ideal world, actual prices should provide market-consistent returns for shareholders and sufficient incentive to innovate.

The EU, a pioneer in gene therapy

European scientists, institutions and charities have been central to the development of gene therapy. The world's first successful clinical trial was reported in 2000 by Alain Fischer and his team at Necker Hospital in Paris, while the first authorisation of a gene therapy product in a regulated market was granted by the European Medicines Agency in 2012.

According to the Cordis database of EU-supported research, 86 gene therapy projects for rare diseases had funding from the European Commission during the FP7 (2007-2013) and Horizon 2020 (2014-2020) research programmes. One can estimate that overall more than 1 billion has been invested in this area by the EU Commission, member states and not-for-profit organisations.

To ensure European patients benefit from these achievements and investments, it is essential to ensure reasonable pricing of gene therapies. Laudable efforts are currently being made by the World Health Organization to increase transparency, and by some member states to join forces in negotiating prices, but such initiatives are unlikely to solve the current crisis as they do not address its root, namely that the sole objective of most gene therapy companies is to maximise the return on investment and shareholder value.

A way forward: enforcing the corporate social responsibility of gene therapy manufacturers

As I recently argued with Alain Fischer and the economist Mathias Dewatripont in the journal Nature Medicine (November 25, 2019), now is the time to reflect on how to enforce the corporate social responsibility of gene therapy companies.

Among the measures we would like to see considered are the insertion of clauses into technology transfer agreements made between academic organisations receiving grants from the European Commission and for-profit companies to make reasonable pricing compulsory.

We also propose to make reimbursement of gene therapies by EU healthcare payers conditional on the companies which are commercialising these products being certified for their corporate social responsibility. This is in line with several commitments made recently by pharma companies. For example, in August 2019, the CEOs of US-based pharma companies signed the Business Roundtable Statement, affirming their commitment to generate value for all their stakeholders not just their shareholders.

Also in August, Novartis announced it had joined the Value Balancing Alliance, a body whose goal is to increase transparency around business decisions, work with external bodies to develop accounting frameworks, and shift priority from profit maximisation to optimising value creation.

Earlier this year, the pharmaceutical company Chiesi was certified as a Benefit Corporation, meaning its legally defined goals include positive social impact in addition to profit.

Of course, the effective implementation of such commitments and their translation into reasonable pricing policies will require both incentives and regulatory controls. The starting point should be a renewed multi-stakeholder conversation with industry, investors, regulators, payers and, of course, patients.

Professor Michel Goldman is Co-director of the I3h Institute at the Universit Libre de Bruxelles and former Executive Director of the EU Innovative Medicines Initiative.

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Viewpoint: EU should take a lead in enforcing the corporate social responsibility of gene therapy manufacturers - Science Business

VGXI has set up an RNA pilot production suite at its facility in Woodlands, Texas citing growing demand from gene therapy developers.

The GMP-grade mRNA manufacturing unit will support customer projects from initial plasmid construction through linearization, in vitro translation, mRNA purification, and comprehensive quality control testing according to VGXI.

VGXI plans to launch clinical grade mRNA manufacturing services next year.

The RNA suite will be set up in Woodlands, near Houston. Image: iStock/gguy44

The pilot plant was set up as part of the VGXI licensing deal with the Houston Methodist Research Institute.

The CDMO said it will continue to work with the Institutes RNACore group a research team focused on RNA synthesis to set up a large-scale GMP mRNA production facility.

In a separate announcement VGXI said it has hired construction services company BE&K Building Group as Design-Build Partner for the initial phase of the manufacturing site.

It said the planned 240,000-square-foot facility will house multiple flexible production suites to support both DNA and RNA-based biopharmaceuticals at all phases of development through commercial supply.

The plant is expected to be operational in two to three years.

The investment is in keeping with the DNA vaccines partnership VGXI forged with Geneos Therapeutics earlier in the year.

The deal will see VGXI make the API, or core component of Geneos Therapeutics DNA vaccine product according to spokeswoman Christy Franco.

VGXI cited growth of the gene therapy sector as the basis for its investment in RNA capacity.

It said, A driving factor for both site selection and building design is available capacity to support VGXIs continued, future expansions to meet growing industry demand.

VGXI has identified and selected a suitable location for the construction project, with approval granted in November for a $1.2 million incentive during a special council meeting by the City of Conroe.

The Texan CDMO joins the growing list of contractors trying to tap the gene therapy sector. In recent months both Fujifilm and Cytovance have cited demand for gene therapy production services as an expansion driver.

The firms comments fit with the dynamics observed by the pharmaceutical research and manufacturers of America (PhRMA).

Accordingto the industry group, at present there are 289 cell and gene therapy products in development, which is a marked increase on previous years.

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VGXI adds RNA suite to tap cell and gene therapy - Bioprocess Insider - BioProcess Insider

One of the most popular methods for inserting therapeutic genes into cells to treat disease is to transport them using a virus that has been stripped of its infectious properties. But those noninfectious viruses can still sometimes touch off dangerous immune responses.

A team from Johns Hopkins Medicine is proposing an alternative method for transporting large therapies into cellsincluding genes and even the gene-editing system CRISPR. Its a nano-container made of a polymer that biodegrades once its inside the cell, unleashing the therapy. The researchers described the invention in the journal Science Advances.

The team, led by biomedical engineer Jordan Green, Ph.D., was inspired by viruses, which have many properties that make them ideal transport vehicles. They have both negative and positive charges, for example, which allows them to get close to cells. So Green and his colleagues developed a polymer containing four molecules with both positive and negative charges. They used it to make a container that interacts with the cell membrane and is eventually engulfed by it.

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The Hopkins researchers performed four experiments to prove the nanocontainers would travel into cells and deliver complex therapies once inside. First, they packaged a small protein into the polymer material and mixed it with mouse kidney cells in a lab dish. Using fluorescent tags, they confirmed that the protein made it into the cells. Then they repeated the experiment with a much larger medicinehuman immunoglobulinand observed that 90% of the kidney cells received the treatment.

From there, they made the payload even bulkier, packaging the nanocontainers with the gene-editing system CRISPR. With the help of fluorescent signals, they were able to confirm that CRISPR went to work once inside the cells, disabling a gene 77% of the time.

"That's pretty effective considering, with other gene-editing systems, you might get the correct gene-cutting result less than 10 percent of the time," said graduate student Yuan Rui in a statement.

Finally, the Hopkins researchers injected CRISPR components into mouse models of brain cancer using the polymer nanocontainers. Again they saw evidence that successful gene editing had occurred.

Developing improved methods for gene therapy is a priority in the field. In October, for example, scientists at Scripps Research described a way to use a small molecule called caraphenol A to lower levels of interferon-induced transmembrane (IFITM) proteins, which could, in turn, allow viral vectors to pass more easily into cells. And earlier this year, an Italian team described a method for including the protein CD47 in lentiviral vectors to improve the transferring of therapeutic genes into liver cells.

The next step for Hopkins researchers Rui and Green is to improve the stability of the nanocontainers so they can be injected into the bloodstream. They hope to be able to target them to cells that have certain genetic markers, they reported.

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Hopkins team invents non-viral system for getting gene therapy into cells - FierceBiotech

Its said that nothing is certain except death and taxes. But doubt has been cast over the former since the 1970s, when scientists picked at the seams of one of the fundamental mysteries of biology: the molecular reasons we get old and die.

The loose thread they pulled had to do with telomeresmolecular timepieces on the ends of chromosomes that shorten each time a cell divides, in effect giving it a fixed life span. Some tissues (such as the gut lining) renew almost constantly, and it was found that these have high levels of an enzyme called telomerase, which works to rebuild and extend the telomeres so cells can keep dividing.

That was enough to win Elizabeth Blackburn, Carol Greider, and Jack Szostak a Nobel Prize in 2009. The obvious question, then, was whether telomerase could protect any cell from agingand maybe extend the life of entire organisms, too.

While telomere-extending treatments in mice have yielded intriguing results, nobody has demonstrated that tweaking the molecular clocks has benefits for humans. That isnt stopping one US startup from advertising a telomere-boosting genetic therapyat a price.

Libella Gene Therapeutics, based in Manhattan, Kansas, claims it is now offering a gene therapy to repair telomeres at a clinic in Colombia for $1 million a dose. The company announced on November 21 that it was recruiting patients into what it termed a pay-to-play clinical trial.

Buyer beware, though: this trial is for an unproven, untested treatment that might even be harmful to your health.

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The company proposes to inject patients with viruses carrying the genetic instructions cells need to manufacture telomerase reverse transcriptase, a molecule involved in extending the length of telomeres.

The dangers are enormous, says Jerry Shay, a world expert on aging and cancer at the University of Texas Southwestern Medical Center. Theres a risk of activating a pre-cancerous cell thats got all the alterations except telomerase, especially in people 65 and over.

For years now, people involved in the company have made shifting claims about the study, raising uncertainty about who is involved, when it might start, and even where it would occur. Trial listings posted in October to clinicaltrials.gov currently show plans for three linked experiments, each with five patients, targeting critical limb ischemia, Alzheimers, and aging, respectively.

Jeff Mathis, president of Libella, told MIT Technology Review that two patients have already paid the enormous fee to take part in the study: a 90-year-old-woman and a 79-year-old man, both US citizens. He said they could receive the gene therapy by the second week of January 2020.

The decision to charge patients a fortune to participate in the study of an experimental treatment is a red flag, say ethics experts. Whats the moral justification for charging individuals with Alzheimers? asks Leigh Turner, at the University of Minnesotas Center for Bioethics. Why charge those bearing all the risk?

The telomere study is occurring outside the US because it has not been approved by the Food and Drug Administration. Details posted to clincaltrials.gov indicate that the injections would be carried out at the IPS Arcasalud SAS medical clinic in Zipaquir, Colombia, 40 kilometers (25 miles) north of Bogot.

It takes a lot longer, is a lot more expensive, to get anything done in the US in a timely fashion, Mathis says of Libellas choice to go offshore.

To some promoters of anti-aging cures, urgency is justified. Heres the ethical dilemma: Do you run fast and run the risk of low credibility, or move slowly and have more credibility and global acceptancebut meanwhile people have died? says Mike Fossel, the president of Telocyte, a company planning to run a study of telomerase gene therapy in the US if it can win FDA signoff.

Our reporting revealed a number of unanswered questions about the trial. According to the listings, the principal investigatorwhich is to say the doctor in charge--is Jorge Ulloa, a vascular surgeon rather than an expert in gene transfer. I dont see someone with relevant scientific expertise, says Turner.

Furthermore, Bill Andrews, who is listed as Libellas chief scientific officer, says he does not know who Ulloa is, even though on Libellas website, the mens photos appear together on the list of team members. He said he believed that different doctors were leading the trial.

Turner also expressed concerns about the proposed 10-day observation period described in the posting for the overseas study: If someone pays, shows up, has treatment, and doesnt stick around very long, how are follow-up questions taking place? Where are they taking place?

Companies seeking to try the telomere approach often point to the work of Maria Blasco, a Spanish scientist who reported that telomere-lengthening gene therapy benefited mice and did not cause cancer. Blasco, director of the Spanish National Centre for Cancer Research, says she believes many more studies should be done before trying such a gene experiment on a person.

This isnt the first time Libella has announced that its trial would begin imminently. It claimed in late 2017 that human trials of the telomerase therapy would begin in the next few weeks. In 2016, Andrews (then partnered with biotech startup BioViva) claimed that construction of an age reversal clinic on the island nation of Fiji would be complete before the end of the year. Neither came to pass.

Similar questions surround Libellas most recent claims that it has two paying clients. Pedro Fabian Davalos Berdugo, manager of Arcasalud, said three patients were awaiting treatment in December. But Bioaccess, a Colombian contract research organization facilitating the Libella trial, said that no patients had yet been enrolled.

Also unclear is where Libella is obtaining the viruses needed for the treatment. Virovek, a California biotech company identified by several sources as Libellas manufacturer, did not answer questions about whether any treatment had been produced.

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Buyer beware of this $1 million gene therapy for aging - MIT Technology Review