Denali Therapeutics Inc. DNLI announced that its meeting with the Center for Drug Evaluation and Research (“CDER”) division of the FDA for the advancement of pipeline candidate tividenofusp alfa (DNL310) was successful.

Tividenofusp alfa (DNL310) is being evaluated for the treatment of MPS II (Hunter syndrome).

The meeting with CDER outlined a path for Denali to file a biologics license application (BLA) seeking accelerated approval of tividenofusp alfa (DNL310) for the treatment of MPS II and its subsequent conversion to full approval.

Shares of this biopharmaceutical company have gained 17.8% in the year to date against the industry’s decline of 1%.

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Denali’s Plans for Tividenofusp Alfa

Denali reached an agreement with the CDER that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II.

As per discussions with CDER, Denali will include preclinical and clinical data on biomarkers (CSF HS and neurofilament light [NfL]) and safety in the BLA for tividenofusp alfa as a treatment of MPS II.

Denali plans to submit the BLA under the accelerated approval pathway in early 2025.

DNLI is currently enrolling in the phase II/III COMPASS study on tividenofusp alfa in North America, South America, Europe and Australia, based on supportive clinical and preclinical data to date. The study will likely enroll approximately 54 participants with MPS II (with and without neuronopathic disease). The participants are randomized 2:1 to receive either tividenofusp alfa or idursulfase.

Data from a phase I/II study showed treatment with tividenofusp alfa produced robust and durable effects, with normalization of key disease biomarkers and improvement or stabilization in associated CNS and somatic clinical endpoints.

Denali Presents New Data on Tividenofusp Alfa

Denali also announced that new interim data from the phase I/II study is currently being presented at the Symposium of the Society for the Study of Inborn Errors of Metabolism. The presentations include data from additional study participants (n=37) and longer duration of treatment with tividenofusp alfa (up to week 129) as well as new analyses on biomarkers and clinical outcomes.

The data showed a 90% mean reduction in CSF HS from baseline at week 24, with all participants having normal or near normal levels at week 24. CSF HS reduction was sustained through week 104.

The proportion of participants with normal total urine glycosaminoglycans (colorimetric method) increased to 77% at week 24 from 5% of participants at baseline. This effect was sustained through week 129.