Vertex Pharmaceuticals, Inc.

Johnson & Johnson’s gene therapy for a genetic disease that leads to vision loss called X-linked retinitis pigmentosa (XLRP) failed a pivotal trial, according to an update to a J&J healthcare provider website. At one year, the gene therapy, called bota-vec, didn’t meet its primary endpoint in the Phase 3 LUMEOS study, though results were “directionally supportive,” according to the website , which appears to have been updated Friday. The primary endpoint measured the change in patients’ ability to navigate through a vision-guided mobility assessment maze. “We’re working to understand the totality of the data, inclusive of the clinical relevance of improvement shown on the majority of secondary endpoints, as we evaluate strategic options and next steps,” a J&J spokesperson told Endpoints News via email. The Phase 3 study fail comes as large biopharma companies are pulling back from AAV gene therapy work. Vertex became the latest company to stop research on AAV gene therapy, Endpoints reported Friday. And Pfizer, Takeda, Roche and Biogen have previously cut back on AAV gene therapy research or clinical programs. J&J acquired the gene therapy, known as bota-vec, from MeiraGTx for $65 million upfront in 2023 after previously making licensing deals for three eye disease gene therapies, including bota-vec, from the smaller biotech. The gene therapy delivers functional copies of the RPGR gene via viral packages called adeno-associated viruses, or AAVs. That gene is mutated in people with X-linked retinitis pigmentosa, a disease that primarily impacts boys and men. The Phase 3 study had enrolled 95 participants and split them into three groups: low-dose gene therapy, high-dose gene therapy, or deferred treatment — a group of patients who served as the comparator arm and were meant to receive the gene therapy after the primary endpoint measurement. A Biogen gene therapy for XLRP failed a mid-stage study in 2021. Beacon Therapeutics is studying a gene therapy for the rare eye disease, and last year raised $170 million. Editor’s note: This story was updated to include a statement from a J&J spokesperson.

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.

Vertex Pharmaceuticals, Amgen and Jazz Pharmaceuticals are among companies that received a positive opinion from European regulators for drugs that are already in the US market. The European Medicines Agency’s human medicines committee (CHMP) said on Friday that it recommended the European Commission to give the go-ahead for six new medicines and 10 label expansions. Among the six new medicines was Vertex’s cystic fibrosis oral therapy called Alyftrek, which was approved by the FDA last December for the same indication. Amgen similarly got a CHMP nod for Tepezza in moderate to severe Thyroid Eye Disease. Tepezza was approved by the FDA for that condition in January 2020. Jazz also secured a positive opinion for its bile duct cancer antibody Ziihera, which was approved by the FDA in November last year. On Friday, the committee said it would re-examine its earlier decision to reject Eli Lilly’s Alzheimer’s drug Kisunla. It also recommends PTC Therapeutics’ drug, dubbed Sephience, to be used to treat hyperphenylalaninemia in patients with the metabolic disease phenylketonuria. The other CHMP medicine recommendations are for Italfarmaco’s therapy Duvyzat for Duchenne muscular dystrophy and Purpose Pharma’s Attrogy for ATTR amyloidosis. As for the 10 label expansions, the committee recommended extending two of Bayer’s drugs, including a new dose of Adempas, which is approved for pulmonary arterial hypertension, as well as extending the label for the hemophilia A drug called Jivi for children aged seven and above. Other label recommendations: The regulators also recommended the EC approve nine new biosimilar products, eight of which were biosimilars to Amgen’s denosumab, which is a treatment for rare bone disease.