FDA rejects Rocket gene therapy due to manufacturing

The Food and Drug Administration (FDA) has rejected Rocket Pharmaceuticals' gene therapy, Kresladi, developed to treat severe leukocyte adhesion deficiency-I, a rare inherited immunodeficiency. This information was disclosed by the biotechnology company on Friday.

Rocket Pharmaceuticals revealed that the FDA requested additional details concerning chemistry, manufacturing, and controls (CMC) to ensure the quality and consistency of the final drug product. The company has already engaged with the FDA to define the specifics of this request, aiming to expedite the process for securing eventual approval.

Gaurav Shah, CEO of Rocket Pharmaceuticals, expressed confidence in the collaborative relationship with the FDA. Shah highlighted the agency's understanding of the critical medical need, the clear clinical benefits, and the importance of timely patient access to the therapy.

The FDA's communication on this matter comes in the form of a complete response letter (CRL), which the agency does not publicly release. Therefore, the nature of the FDA's feedback is known only through the company's disclosure. Despite this, Wall Street analysts who have interacted with Rocket remain optimistic, viewing the rejection as a temporary obstacle rather than a permanent setback for Kresladi.

Dae Gon Ha, an analyst at Stifel, conveyed in an investor note that the eventual approval of Kresladi is anticipated, suggesting that it is a matter of timing rather than possibility. The FDA had previously extended its decision on Kresladi by three months due to a change in the reviewing personnel, thereby exhausting the option for further evaluation delays. Ha interpreted the issuance of the CRL as a reluctant measure on the FDA's part, reflecting no major deficiencies in the submission package.

Similar sentiments were echoed by analysts at William Blair and Chardan. William Blair's analyst, Sami Corwin, attributed the CRL to possible staffing constraints within the FDA rather than issues with Kresladi's critical attributes.

Kresladi is designed using a patient's own stem cells, which are genetically altered to introduce a functional copy of the mutated gene responsible for the condition. Severe leukocyte adhesion deficiency-I significantly compromises the body's ability to combat infections, leading to frequent bacterial and fungal infections in infants, often requiring hospitalization. Survival beyond childhood without a successful bone marrow transplant is rare.

In Rocket's trial, all nine patients treated with Kresladi survived through the follow-up period, ranging from 18 to 42 months. The data indicated a reduction in significant infections and improvement in disease-related skin conditions.

Despite potential resolutions to the FDA's issues with Rocket's application, this rejection represents another challenge for the gene therapy field, which has encountered numerous clinical, regulatory, and business difficulties. Manufacturing remains a particularly complex area for developers. For instance, Abeona Therapeutics experienced a similar rejection from the FDA for its skin disease cell therapy earlier this year.

Additionally, large pharmaceutical companies like Daiichi Sankyo and AbbVie have faced their own manufacturing-related CRLs for drugs submitted for FDA approval, underscoring the broader challenges within the industry.