Vertex Pharmaceuticals has halted all research on adeno-associated virus (AAV) vector technology, marking another significant retreat in the gene therapy space that has seen multiple pharmaceutical giants scale back their investments in recent months.
According to reports from Endpoints News, Vertex has terminated its AAV platform work, potentially affecting several key partnerships. Affinia Therapeutics confirmed it has regained rights to Duchenne muscular dystrophy (DMD) vectors that were part of a $1.6 billion collaboration established in 2020. Vertex had previously returned rights to cystic fibrosis-targeting vectors to Affinia in 2022.
The decision also impacts Vertex's partnership with Tevard Biosciences, which was developing tRNA therapies for DMD using AAV delivery systems. Tevard received notification late last year that Vertex was exiting the DMD deal and has since regained rights to its tRNA program.
Industry-Wide Retreat from AAV Technology
Vertex's move follows similar decisions by other pharmaceutical companies to scale back AAV research:
- Pfizer discontinued the global rollout of its FDA-approved hemophilia B gene therapy Beqvez in February, citing "limited interest patients and their doctors have demonstrated in hemophilia gene therapies"
- Roche significantly restructured its AAV-focused gene therapy unit Spark Therapeutics, laying off more than half the staff
- Takeda abandoned its preclinical AAV gene therapy programs in 2023
- Biogen cut its preclinical AAV gene therapy pipeline amid rising safety concerns
This industry-wide retreat comes after years of optimism surrounding AAV vectors, which have been used in several approved gene therapies including Luxturna, Zolgensma, Elevidys, Hemgenix, and Roctavian.
Limitations Driving the AAV Exodus
Philippe Chambon, founder and CEO of French biotech EG 427, explained that several factors are driving pharmaceutical companies away from AAV-based therapies:
"Pharma is pulling away from AAV-based gene therapies because of several challenges preventing their effective and cost-effective use beyond rare diseases," said Chambon. "To unleash the real potential of gene therapy as a significant drug modality, it must be able to address diseases beyond the rare disease field and tackle chronic indications."
Key limitations of AAV vectors include:
- Limited payload capacity: AAVs can only carry approximately 4.7Kb of genetic material, restricting their utility for delivering larger genes
- Manufacturing challenges: Production of AAV vectors is complex and expensive to scale
- Safety concerns: Immunogenicity issues have raised safety questions in clinical development
- Re-dosing limitations: The "one-and-done" paradigm creates therapeutic and economic challenges
Broader Impact on Gene Therapy Development
Vertex's AAV pullback is part of a larger pattern of recalibration in the cell and gene therapy space. Several companies have reduced workforces in recent months, including Encoded Therapeutics, Intellia Therapeutics, and Editas Medicine. Editas was forced to discontinue its sickle cell disease gene therapy renizgamglogene autogedtemcel after failing to find a development sponsor.
The retreat from AAV technology also follows Vertex's decision in February to end a partnership with Verve Therapeutics, returning rights to an in vivo liver disease gene editing program. In March, Vertex discontinued its pancreatic islet cell therapy for type 1 diabetes.
The Search for Alternative Delivery Systems
Despite the industry pullback, some companies remain committed to advancing AAV technology. Affinia Therapeutics continues to design improved capsids that "better target tissues and cells that are the desired sites of efficacy while avoiding sites of toxicity" through re-engineering AAV9 by integrating short peptides into the AAV genetic sequence.
Meanwhile, other companies are exploring alternative viral vectors. EG 427 is developing genetic medicines based on non-replicative Herpes simplex virus-1 (HSV-1) vectors, which can carry genetic payloads exceeding 30kb—more than six times larger than AAV vectors.
"We believe this approach provides an alternative that has already demonstrated safety clinically, offers the possibility to re-dose, easier to scale manufacturing cost-effectively, and possesses an inherently large payload capacity at least six times bigger than AAV," said Chambon.
As the gene therapy field continues to evolve, the focus appears to be shifting toward developing delivery systems that can overcome the limitations of AAV vectors, potentially opening new therapeutic possibilities for a broader range of diseases beyond rare genetic disorders.
