Yahoo Finance

Denali Therapeutics DNLI reported primary analysis data from an early to mid-stage study of its pipeline candidate, tividenofusp alfa (DNL310), in 47 patients with Hunter syndrome (MPS II) over a 24-week treatment period, along with additional long-term follow-up data. DNLI’s wholly-owned program, tividenofusp alfa, is an Enzyme Transport Vehicle-enabled iduronate-2-sulfatase replacement therapy in development for MPS II.

Per the additional long-term data readout from the phase I/II study, treatment with tividenofusp alfa resulted in significant and substantial reductions in key disease biomarkers within the central nervous system and peripheral system, bringing them to normal or near-normal levels. Such biomarkers included cerebrospinal fluid and urine heparan sulfate, as well as neurofilament light, a recognized marker of neurodegeneration.

Per Denali, such efficacy data suggests the pervasive nature of treatment effects in MPS II patients over the longer term.

Shares of DNLI have plunged 28.1% in the past three months compared with the industry’s decline of 6.6%.

Image Source: Zacks Investment Research

The therapy led to meaningful clinical outcomes, including normalized liver volume after 24 weeks, continued improvement in hearing thresholds across all tested frequencies, and notable skill gains in most participants in adaptive behavior and cognitive assessments. Moreover, the candidate was generally safe and overall well-tolerated by MPS II patients.

Treatment-related adverse events were mostly mild to moderate in severity. Denali reported that there were three cases of serious adverse events that were manageable with continued treatment. However, one MPS II patient discontinued treatment due to a moderate infusion-related reaction and other non-treatment-related adverse events.

These additional longer-term data will be presented at an upcoming medical conference in San Diego, CA.

Recent Regulatory Updates on DNLI’s MPS II Program

Last month, Denali announced that the FDA has granted Breakthrough Therapy Designation to tividenofusp alfa for the MPS II indication. This designation is intended to expedite the development and review of therapeutic drugs, which are being evaluated for the treatment of serious or life-threatening conditions. Additionally, the candidate also enjoys the FDA’s Fast Track designation in the United States for the same indication. In 2022, the European Medicines Agency granted Priority Medicines designation to tividenofusp alfa for MPS II.

In September 2024, Denali announced the outcome of a successful meeting with the FDA, providing a path to filing a biologics license application (BLA) for tividenofusp alfa for accelerated approval and subsequent conversion to full approval for the treatment of Hunter syndrome.