We are pleased to share that Denali Therapeutics has just announced positive preliminary cerebrospinal fluid heparan sulfate (CSF HS) biomarker data for its Phase 1/2 study of DNL126 in Sanfilippo Syndrome Type A (MPS IIIA).
Denali stated in a public third-quarter report on its website:
“Preliminary data from our Phase 1/2 study of DNL126 in MPS IIIA demonstrate a robust reduction from baseline in CSF heparan sulfate levels, including normalization. Based on these data and a positive regulatory environment, we recently expanded the study to support a potential accelerated path, said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics.”
- Preliminary data from up to 25 weeks of dosing in the ongoing open-label Phase 1/2 study in MPS IIIA participants demonstrate a significant reduction in CSF HS levels from baseline, including normalization.
- The safety profile supports continued development. The most frequent treatment emergent adverse events were infusion related reactions of mild and moderate severity in all participants. There was one serious adverse event considered by the investigator not related to drug. Denali plans to present the data at a future medical meeting.
- Based on the preliminary Phase 1/2 results and a positive regulatory environment, Denali recently expanded the study and continues to assess the development plans including an accelerated approval path.
- DNL126 was selected in June 2024 for the FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) program to accelerate the development of rare disease therapeutics, and collaborative engagement has commenced to support progress to a pre-BLA meeting.
Denali provided the following additional information to Cure Sanfilippo Foundation regarding the DNL126 study to share:
Q: When do you plan to present data at an upcoming medical meeting?
A: At this time, we have not finalized plans for when and where we will share data from the ongoing Phase 1/2 study. Once we determine our presentation plans and a publication has been publicly accepted, we will share this information.
Q: Can you share details of the study expansion mentioned in this update?
A: This expansion refers to the recent opening of enrollment in Cohorts A3, B1, and B2 in the Phase 1/2 study. Details on these cohorts can be found on https://clinicaltrials.gov/study/NCT06181136. As previously shared, all participants for A1, A2, and A3 have been identified. Our focus remains on identifying the most effective and timely path to advance DNL126 as a potential treatment for the MPS IIIA community.
Q: How does being part of the FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) pilot program impact the development of DNL126?
A: Being part of this program enables us to work closely with the FDA to further accelerate the development path for DNL126. We look forward to working collaboratively with the FDA on this effort.
What is DNL126?
DNL126 is a first-in-human Phase I/II study that is testing the safety and efficacy of the experimental enzyme replacement drug named DNL-126. In this study, DNL-126 is given by infusion into a central venous port which is a device that is implanted under the skin of the chest and into a deep vein. This study currently has several active clinical sites in the USA, and is enrolling up to 4 children in cohort B1 [severe phenotype, age <28 months of age (2 years, 4 months)] and up to 4 children in cohort B2 (sibling of child enrolled in cohort B1 and <18 years of age). Follow ClinicalTrials.gov for ongoing study status and enrollment updates.