DNLI's Hunter Syndrome Drug Gets Breakthrough Therapy Designation

Core Insights - Denali Therapeutics Inc. (DNLI) has received Breakthrough Therapy Designation from the FDA for its candidate tividenofusp alfa (DNL310) aimed at treating Hunter syndrome (MPS II) [1][2] Group 1: FDA Designation and Implications - The Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions, indicating that tividenofusp alfa may offer substantial improvement over existing therapies [2] - This designation will provide Denali with more intensive guidance from the FDA, including involvement of senior reviewers and eligibility for rolling and priority review of the marketing application [3] Group 2: Clinical Development and Future Plans - Data from an open-label phase I/II study have shown promising results, with positive effects on surrogate endpoints and early signs of improved clinical outcomes in Hunter syndrome participants [3] - Denali plans to submit a Biologics License Application (BLA) for tividenofusp alfa in early 2025 under the accelerated approval pathway [5] Group 3: Recent Pipeline Updates - Denali has initiated dosing in a global mid-stage study, BEACON, for BIIB122 (DNL151), an investigational LRRK2 inhibitor for Parkinson's disease [6] - BIIB122 is also being evaluated in the ongoing global phase IIb LUMA study, which aims to enroll approximately 640 participants with early-stage Parkinson's disease [8] Group 4: Disappointing Results and Discontinuations - Denali reported disappointing results from the phase II/III HEALEY ALS Platform Trial for DNL343, which did not meet its primary endpoint of efficacy in slowing disease progression [9][10] - Partner Sanofi has discontinued the development of SAR443820/DNL788 for ALS and multiple sclerosis due to failure to meet primary and key secondary endpoints in clinical studies [11][12]