Takeda, Denali’s Alzheimer’s candidate drug hits regulatory drawback

USA – The FDA has placed a clinical hold on Denali Therapeutics’ Alzheimer’s drug before it even enters human trials.

The decision has an impact on Takeda, which only recently decided to move forward with the pair’s 2018 agreement by opting to co-develop the drug.

The news of the hold sent Denali shares down 13% just days after partner Takeda exercised its option to co-develop and co-commercialize the drug.

Takeda paid Denali US$150 million in advance as part of the two companies’ 2018 collaboration agreement to develop neurodegenerative disease treatments, including DNL919.

According to the biotech, Triggering receptor expressed on myeloid cells 2 (TREM2) function loss is associated with an increased risk of Alzheimer’s.


DNL919 is an antibody transport vehicle (ATV) designed to activate TREM2 and improve microglial function. The ATV drug aims to activate TREM2 in the hope of improving microglial function, or “resident immune cells of the brain,” according to Denali.

Denali had hoped to perform clinical trials of test DNL919 this year. Other investigational medications are being tested in Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and other conditions.

This isn’t Takeda’s first setback in Alzheimer’s drug development. After failing to convert an approved diabetes medication into an Alzheimer’s treatment, the pharmaceutical and its partner Zinfandel Pharmaceuticals canceled a phase 3 trial called TOMORROW in January 2018.

Denali did not elaborate on what prompted the regulatory halt, but stated that it “plans to provide additional updates pending discussion with the FDA.”

Prior to receiving the FDA notice, Denali stated earlier this week that, pending approval of the IND application, it planned to begin first-in-human clinical trials of DNL919 in Alzheimer’s disease in the first half of the year, with human safety and biomarker data available in the second half.

It went on to say that animal model results showed “enhanced brain uptake” with DNL919 when compared to a non-ATV TREM2 antibody, as well as improved pharmacodynamic response.

In the past year, the Alzheimer’s field has been buoyed by a surge of investor and scientific interest, particularly since the FDA’s contentious approval of Biogen’s Aduhelm.

That drug has received widespread criticism, including a proposal this week from the Centers for Medicare & Medicaid Services that Medicare will cover Aduhelm but only for patients enrolled in qualifying clinical trials. The proposal has since received approval from industry groups.

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