FDA Places Hold on Denali's Pompe Disease Trial, Delays Hunter Syndrome Drug Decision
Denali Therapeutics faces regulatory challenges as the FDA puts a hold on its planned Phase I trial for a Pompe disease treatment and postpones a decision on its Hunter syndrome therapy. These setbacks come amid a series of clinical and regulatory hurdles for the Bay Area biotech company.
Clinical Hold on Pompe Disease Therapy
The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Denali Therapeutics' Investigational New Drug (IND) application for DNL952, an experimental enzyme replacement therapy for Pompe disease. The hold, disclosed in a recent SEC filing, was prompted by hypersensitivity reactions observed in preclinical mouse studies.
Denali's DNL952 utilizes the company's proprietary Enzyme Transport Vehicle technology to deliver the therapy across the blood-brain barrier and into muscles. The treatment aims to restore levels of the GAA enzyme, which is deficient in Pompe disease patients, leading to glycogen buildup in various organs.
In response to the FDA's concerns, Denali must implement several protocol changes before initiating the Phase I study, including:
- Lowering the starting dose
- Revising inclusion criteria
- Adjusting stopping rules
- Implementing additional safety monitoring measures
Despite the setback, Denali remains optimistic about the timeline for DNL952's development. 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 also intends to submit a clinical trial application in Europe in the first half of 2026.
Delayed Decision on Hunter Syndrome Treatment
In a separate development, Denali announced that the FDA has extended its review period for tividenofusp alfa (tivi), the company's investigational treatment for Hunter syndrome. The regulator pushed back its target action date to April 5, 2026, citing the need to review updated pharmacological information submitted by Denali.
This delay comes at a critical time for Denali, as tivi represents the company's potential first market launch. To bolster its financial position and support ongoing development programs, Denali has entered into a $275 million financing deal with Royalty Pharma. Under the agreement, Denali will receive $200 million upon tivi's approval, with Royalty Pharma entitled to 9.25% royalty payments on worldwide sales until certain conditions are met.
CEO Ryan Watts, Ph.D., emphasized that the Royalty deal is intended to strengthen Denali's development programs as the company prepares for tivi's potential market debut.
References
- FDA Pauses Denali’s Pompe Plans Due to Preclinical Safety Signals
Hypersensitivity reactions in a mouse model prompted the agency to suspend Denali’s planned Phase I development for DNL952 for Pompe disease.
- 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 are the major competitors currently developing treatments for Pompe disease, and how do their approaches differ from Denali's DNL952?
What preclinical or clinical safety data exists for other therapies utilizing Enzyme Transport Vehicle technology?
What is the anticipated market size for Hunter syndrome treatments, and how does tividenofusp alfa's profile compare to existing or upcoming therapies?
What milestones does Denali need to achieve to solidify its financial position, particularly in light of the $275 million financing deal with Royalty Pharma?
How does the FDA's feedback process impact the projected timelines and success rates of Denali's therapies in the pipeline?