Takeda’s Denali Fails Initial Alzheimer’s Drug Trials — Possible Unwieldy Treatment Uncovered

After studying the initial Phase I findings of an experimental Alzheimer’s therapy, Takeda and Denali Therapeutics have concluded that the treatment had a “narrow therapeutic window” and have thus ended their joint investigation into its effectiveness.

In 2018, two companies began exploring groundbreaking opportunities in neurodegenerative treatment. Fast forward to 2021, and the companies are now partnering to create a game-changing drug collaboration using an antibody transport vehicle (ATV) called DNL919, designed to activate the TREM2 receptor. With a vested interest in providing new and innovative therapies, this collaboration could be a major breakthrough in the medical world.

Denali’s ambitions of bringing a much-needed treatment for Alzheimer’s patients surged forward this July with the FDA clearing its drug – ATV – to enter clinical trials. This promising therapy targets the receptor that is believed to be mostly responsible for the decline in function associated with the risk of Alzheimer’s, with the aim of positively influencing microglial function. Early Phase I data appears to provide strong evidence that this treatment could be incredibly beneficial for those suffering from cognitive decline.

In its second-quarter financial results reported Tuesday, Denali reported an impressively positive outcome for its data having shown “robust target engagement and effects on microglial biomarkers”, as well as the drug having been “clinically well tolerated at doses with demonstrated changes” lacking in any serious or severe side effects.

The companies recently revealed their findings from a study on a drug meant to treat Alzheimer’s disease. Unfortunately, the data showed evidence of “safety signals” with moderate and reversible hematolic effects, presenting a difficult and narrow therapeutic window for this specific patient population, prompting the companies to drop the drug from further development.

As it turns out, the rapidly advancing treatment landscape for Alzheimer’s disease nowadays emphasizes the synergy of newly approved therapies, making the decision for the companies to abandon this particular drug much easier.

Denali Pharmaceuticals and Biogen have reported less-than-ideal safety results regarding their prospected treatments, DNL919 and TREM2, however this doesn’t mean the end of hope. The companies remain adamant that research should be continued on their back-up molecules, including exploring potential combination therapies as a result of recent drug approvals for Alzheimer’s treatment. They believe that the safety findings are specific to the properties of DNL919 and TREM2 biology, leaving the door open for potential effective therapies in the future.

With DNL919 scrapped, the focus for Biogen, Eisai and Eli Lilly has shifted to amyloid-targeting therapies. Already successful in this area, they have their monoclonal amyloid antibody treatment, Leqembi, approved by the FDA, and Eli Lilly’s donanemab is currently being tested in Phase III clinical trials. As a result, these companies are making strides towards more effective treatment strategies for Alzheimer’s Disease.

Denali and Biogen recently joined forces to accelerate research and development for Alzheimer’s and Parkinson’s disease. Through their partnership, Biogen has exercised their option to Denali’s ATV-amyloid-beta program for Alzheimer’s. The two have also revised their BIIB122 (LRRK2 inhibitor’s) clinical development plan with one key goal in mind – increasing efficiency by focusing on one study in Parkinson’s disease. These strategic decisions show the power of the Denali-Biogen partnership and their commitment to finding cures for these brain-altering conditions.

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