Rocket's LAD-I gene therapy Kresladi hits FDA manufacturing snag

After an extended review, the FDA issued a complete response letter (CRL) for Rocket Pharmaceuticals' Kresladi (marnetegragene autotemcel), a lentiviral vector-based gene therapy aimed at treating severe leukocyte adhesion deficiency-I (LAD-I). According to the company, the FDA's decision is based on a request for additional chemistry, manufacturing, and controls (CMC) information needed to finalize the review. This setback follows the FDA's earlier extension of the review period by three months in February to assess clarifying information about Rocket's CMC process.

Despite the hurdle, Rocket's CEO Gaurav Shah remains hopeful. The company has already engaged with senior leaders from the FDA's Center for Biologics Evaluation and Research (CBER) to align on the "limited scope of additional CMC information" required for Kresladi's approval.

Investor sentiment mirrored Shah’s optimism. Although Rocket's shares fell by 13% during midmorning trading, they recovered to close nearly flat later in the day. Shah expressed his confidence in the FDA's collaborative approach, emphasizing the high unmet medical need, the clear clinical benefits of the therapy, and the importance of timely patient access. He noted the involvement of CBER leadership and their commitment to working quickly to provide this therapy to patients, which gives the company significant hope for the primary immunodeficiency community.

The Phase I/II study results for the gene therapy showed promising outcomes. There was a 100% overall survival rate at 12 months post-infusion for all nine pediatric LAD-I patients, with follow-up periods ranging from 18 to 42 months. The therapy also led to significant reductions in infection rates compared to pre-treatment history, as well as improvements in LAD-I-related skin lesions and wound healing capabilities.

This regulatory challenge for Rocket Pharmaceuticals contrasts with recent positive developments in the gene therapy sector. Just earlier in the week, the FDA approved an expanded label for Sarepta Therapeutics' Duchenne muscular dystrophy gene therapy, Elevidys (delandistrogene moxeparvovec-rokl), despite mixed clinical data. The decision was somewhat controversial as CBER director Peter Marks overruled other dissenting members within the agency, raising questions about the FDA's approach to gene therapy approvals.