Vertex is pulling back on its genetic medicine research, ending all work related to adeno-associated viruses, or AAVs — the viral vectors commonly used to deliver gene therapies into the body, the company confirmed to
Endpoints News
.
The cuts impact Vertex’s collaborations with at least two biotech startups: the AAV design company Affinia Therapeutics and tRNA therapy company Tevard Biosciences, which uses AAVs. It also calls into question Vertex’s work on CRISPR therapies for genetic muscle diseases.
Several bigger pharmaceutical companies, including
Biogen
,
Pfizer
,
Roche
and
Takeda
, have cut or pared back on AAV gene therapy research in recent years. And several gene therapy biotech companies have trimmed their pipelines and staff as private and public investors sour on the field.
This change of fortune was seemingly unimaginable a few years ago. AAV technology ushered in a new era of gene therapy investment and led to several commercial products for diseases, including Roche’s Luxturna for childhood blindness, Sarepta Therapeutics’ Elevidys for Duchenne muscular dystrophy, and Novartis’ Zolgensma for an otherwise fatal neurodegenerative condition in infants.
But a panoply of challenges — including costly manufacturing, multimillion-dollar drug prices, slow progress in improving targeted delivery and lingering safety issues — has raised questions about the future of AAV medicines.
Vertex did not have any AAV gene therapies in clinical development, despite work on the technology stretching back to at least 2019 when it
acquired
Exonics Therapeutics for its early-stage CRISPR therapies for two muscle diseases: Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1).
Exonics relied on AAV vectors to deliver its therapies
to muscles. Vertex has shared few updates on the program since its acquisition. The approach was essentially a permanent version of the commercial exon-skipping therapies for DMD, meaning it wouldn’t fully restore the dystrophin protein that’s broken in people with the disease.
A Chinese biotech called HuidaGene has developed a similar CRISPR therapy and has already treated two boys,
Endpoints reported last month
. The first patient had modest improvement in his walking ability three months after the treatment.
It is unknown why Vertex’s own CRISPR therapy has seemingly lagged behind. It is possible that the company is holding out for a more curative approach. It may also have been spooked by multiple deaths in people who received the high doses of AAV needed to reach the body’s many muscles, including two from
Pfizer’s experimental therapy
, one from
Sarepta’s approved drug
and one from a
custom CRISPR therapy
.
Heather Nichols, a spokesperson for Vertex, confirmed that the company has discontinued its AAV work, but in an email said that the company’s “commitment to cell and genetic therapies remains strong” and that other investments in DMD and DM1 continue. The company declined to provide further comment on its AAV cuts or make an executive available for an interview.
The need for better AAVs, ones that could deliver more of the therapy at lower doses, has been clear for years.
Vertex struck a partnership with Affinia in 2020 worth up to $1.6 billion for access to the startup’s viral vectors
designed to better target the muscles for treating DMD and DM1 and target the lungs to treat cystic fibrosis, the disease responsible for most of the company’s $11 billion revenue last year.
Affinia CEO Rick Modi told Endpoints in an email that his company regained the rights to its muscle-targeting viruses from Vertex in March. He said the earlier work on cystic fibrosis ended in 2022 and rights to those programs were returned then.
The startup is currently focused on finishing preclinical studies and designing a clinical trial for its lead candidate, for a heart condition called BAG3 dilated cardiomyopathy.
Modi said that Affinia received “the maximum amount of milestone payments” for the research phase of its DMD and DM1 collaboration with Vertex, but he wouldn’t specify the amount. He added that Affinia is looking to license its newly-regained muscle capsids to other companies.
Vertex’s step back from AAVs also impacts Tevard Biosciences. The small startup, which is housed in
Eli Lilly’s genetics-focused research center
that opened in Boston last summer, struck a four-year partnership with Vertex in February 2023 to develop a new class of genetic medicines known as tRNA therapies.
In nature, tRNA molecules are part of the machinery that cells use to translate genetic code into proteins. Tevard is one of a few companies developing synthetic versions of these molecules to help skip over genetic mutations that prevent cells from making fully functional proteins.
Tevard believes its approach could help restore the vital dystrophin protein missing from the muscles of the 15% of people with DMD whose disease is caused by so-called nonsense mutations. While some companies are trying to package tRNA therapies in lipid nanoparticles, those delivery vessels are not readily taken up by the body’s many muscles, so Tevard planned to use AAVs to deliver its treatment.
“We were doing great. The collaboration was going great. But in December, we were informed that they were realigning priorities, and multiple programs were being terminated, including this one,” Tevard CEO Daniel Fischer told Endpoints in an interview. “Two weeks ago, we got the rights back to this program.”
Other tRNA companies have also struggled, including HC Bioscience, which shut down in March after “challenges in targeted delivery,”
Endpoints previously reported
.
Fischer said the fate of the DMD program will depend on whether Tevard can find another drugmaker to partner with or raise enough money to move it forward on its own. The company is planning to present data showing that the DMD therapy works in mice at the upcoming American Society of Gene & Cell Therapy meeting later this month.
