Denali’s DNL126 (MPS IIIA) program selected for FDA’s START pilot

June 4, 2024

Cure Sanfilippo Foundation is thrilled to see that a Sanfilippo program has been selected for FDA’s new START pilot program, intended to improve efficiency of drug development by increasing the frequency and timeliness of product specific regulatory communications.

“Congratulations to the Denali team and to the Sanfilippo community!” said Cure Sanfilippo Foundation Chief Science Officer and Co-Founder Cara O’Neill, MD, FAAP.

According to a press release from the FDA

Today, the U.S. Food and Drug Administration is taking steps to help further accelerate the development of novel drug and biological products for rare diseases. The agency is announcing the opportunity for a limited number of sponsors to participate in a pilot program allowing for more frequent communication with FDA staff to provide a mechanism for addressing clinical development issues.

“We hope the insight gained from this pilot will provide information on how best to facilitate more efficient development of potentially life-saving therapies with rare disease indications and help sponsors generate high-quality, compelling data to support a future marketing application,” said Peter Marks, M.D., Ph.D, director of the FDA’s Center for Biologics Evaluation and Research. “These are complex products and we recognize the importance of sponsor communication with the FDA to facilitate development of products for patients with unmet medical needs.”

Selected participants of the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program will be able to obtain frequent advice and regular ad-hoc communication with FDA staff to address product-specific development issues, including, but not limited to, clinical study design, choice of control group and fine-tuning the choice of patient population.

The program will be open to sponsors of products currently in clinical trials under an active Investigational New Drug application (IND), regulated by the Center for Biologics Evaluation and Research (CBER) and/or the Center for Drug Evaluation and Research (CDER). Eligibility criteria for the pilot differs between CBER and CDER-regulated products.

Denali Therapeutics shared news of its inclusion in the START pilot program in a press release

Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative and lysosomal storage diseases, today announced that the U.S. Food and Drug Administration (FDA) has selected DNL126 for participation in the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program. DNL126 is an investigational enzyme replacement therapy designed to cross the BBB for the potential treatment of MPS IIIA (Sanfilippo syndrome type A).

The FDA announced the START Pilot Program on September 29, 2023, with the stated purpose to further accelerate the pace of development of novel drug and biological products that are intended to address an unmet medical need as a treatment for a rare disease. Selected participants of the START Pilot Program are provided opportunities to obtain frequent advice and engage in more rapid ad hoc communication with FDA review staff to address product-specific development issues. The START pilot and metrics are milestone driven and agreed upon by the FDA and sponsor. Initial selection for START planned to include up to six eligible programs (three each) from the FDA’s Center for Biologics Evaluation and Research’s (CBER) Office of Therapeutic Products and Center for Drug Evaluation and Research’s (CDER) Office of New Drugs.1

“We are thrilled to be selected by the FDA for participation in START and see this as another important opportunity to work together to solve challenges unique to rare disease drug development,” said Carole Ho, M.D., Chief Medical Officer of Denali. “It is an exciting time to be part of the collective effort of making new treatments available to individuals and families living with rare diseases. We look forward to continued collaboration with CDER to determine the most efficient development path for DNL126 in MPS IIIA, a devastating and progressive disease for which treatments are urgently needed.”

Denali is conducting a Phase 1/2 study of DNL126 for children with MPS IIIA, which has generated high interest from the MPS IIIA community for whom there are no approved treatment options. As a selected START participant, Denali anticipates the increased level of engagement will facilitate alignment on the most efficient development path to ultimately support a marketing application for DNL126 in MPS IIIA.

Denali is also developing tividenofusp alfa (DNL310) as a potential treatment for people living with MPS II (Hunter syndrome) and expects to complete enrollment of the Phase 2/3 COMPASS study this year. Given the advanced development stage of the program, Denali did not apply to START for tividenofusp alfa. The FDA granted Fast Track designation to tividenofusp alfa, which also facilitates increased communication and engagement with the FDA specific to this program.

About MPS IIIA (Sanfilippo syndrome Type A)
MPS III, also called Sanfilippo syndrome, is a rare, genetic lysosomal storage disease that causes neurodegeneration. There are four main types of MPS III, depending on the enzyme affected. Type A is caused by genetic defects that result in reduction in the activity of N-sulfoglucosamine sulfohydrolase (SGSH), an enzyme responsible for degrading heparan sulfate in the lysosome. There are no approved treatments for MPS IIIA. A natural history study of biomarkers and adaptive behavior in MPS IIIA is ongoing and more information can be found here.

About DNL126 (ETV:SGSH)
DNL126 (ETV:SGSH) is an investigational, intravenously administered, Enzyme Transport Vehicle (ETV)-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy designed to cross the BBB via receptor-mediated transcytosis into the brain and to enable broad delivery of SGSH into cells and tissues throughout the body with the goal of addressing the behavioral, cognitive, and physical manifestations of MPS IIIA.

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