FDA Places Hold on Denali's Phase 1 Pompe Disease Trial, Citing Preclinical Immune Reactions
Denali Therapeutics faces a setback as the U.S. Food and Drug Administration (FDA) has placed a hold on the company's plans to initiate a phase 1 trial for its rare disease treatment. The regulatory action, disclosed in a December 4 SEC filing, stems from concerns about immune reactions observed in preclinical mouse studies.
FDA Requests Protocol Adjustments
The FDA's decision came during the 30-day review of Denali's Investigational New Drug (IND) application for DNL952, an enzyme replacement therapy targeting Pompe disease. The agency has requested that Denali modify its trial protocol to include:
- A lower starting dose
- Revised inclusion criteria
- Enhanced safety monitoring commitments
- Specific stopping rules
Importantly, the FDA is not requiring additional preclinical research, suggesting that the concerns are manageable within the clinical trial framework.
Denali's Response and Timeline
Despite the setback, Denali remains optimistic about its development timeline. A company spokesperson stated, "We have submitted our response to the FDA and plan to start the phase 1 study in the first half of 2026, pending the agency's feedback."
The biotech does not anticipate significant delays to its phase 1 plans and intends to proceed with a clinical trial application in Europe during the first half of next year.
Broader Context: Pompe Disease and Hypersensitivity Reactions
DNL952 is designed to restore acid alpha-glucosidase (GAA) in patients with Pompe disease, a rare genetic disorder characterized by the buildup of glycogen in cells, leading to progressive muscle weakness. The FDA's concerns center on hypersensitivity reactions observed in preclinical studies.
Denali notes that such reactions are common in mouse models of Pompe disease and have been observed in patients treated with enzyme replacement therapies. This context suggests that while the FDA's caution is warranted, it may not be an insurmountable obstacle for DNL952's development.
References
- FDA slaps hold on Denali's plans for phase 1 rare disease trial
The FDA has placed a hold on Denali Therapeutics’ plans to launch a phase 1 rare disease trial, citing concerns about immune reactions to the investigational treatment recorded in preclinical mouse studies.
Explore Further
What specific immune reactions were observed in the preclinical mouse studies that prompted the FDA's hold?
What are the key efficacy and safety challenges commonly associated with enzyme replacement therapies for Pompe disease?
What are the regulatory and competitive hurdles Denali Therapeutics may face if it proceeds with its clinical trial application in Europe?
Are there any currently approved enzyme replacement therapies for Pompe disease, and how does DNL952 compare to them?
What is the estimated market size for Pompe disease treatments, and how significant is Denali's potential market share?