Astellas Pharma has announced a significant restructuring of its gene therapy portfolio, discontinuing three preclinical candidates for Duchenne muscular dystrophy (DMD) and booking a $170 million impairment charge for its fourth quarter financial results.
The Japanese pharmaceutical company's decision affects gene therapy candidates AT702, AT751, and AT753, all of which were in preclinical development for DMD. This move comes in the wake of ongoing challenges with AT132, the company's gene therapy candidate for X-linked myotubular myopathy (XLMTM), which faced a FDA clinical hold following four patient deaths potentially linked to liver-related adverse events.
Pipeline Restructuring and Financial Impact
Beyond the DMD programs, Astellas is also terminating the development of two other early-stage candidates: ASP2390, a DNA vaccine targeting house dust mite-induced allergic rhinitis, and ASP1951, a GITR agonist antibody being investigated for cancer treatment.
The full financial implications of these program terminations, including the AT132 delay, will be detailed in Astellas' upcoming fourth-quarter results announcement on April 27. This recent $170 million charge follows a more substantial $540 million impairment recorded last year related to the AT132 clinical hold.
Safety Concerns and Vector Platform
The setbacks in Astellas' gene therapy programs, largely acquired through its $3 billion acquisition of Audentes Therapeutics, have raised questions about the safety of their adeno-associated virus (AAV) delivery platform. Research has indicated that systemic administration of AAV vectors may potentially cause liver cell damage and inflammation.
However, in a recent development, Astellas reported interim data from a phase 1/2 trial of AT845 for Pompe disease, which uses the same vector as AT132. The preliminary results from four patients showed no signs of liver toxicity, though the small sample size limits definitive conclusions.
Strategic Implications
The company has indicated a revision of their eligible treatment population projections based on anticipated future product labeling, though specific details remain undisclosed. This strategic realignment reflects the broader challenges facing gene therapy development, particularly regarding safety considerations and regulatory requirements.
