FDA Puts Hold on Plans to Start Clinical Testing of DNL919 Therapy

Marisa Wexler MS avatar

by Marisa Wexler MS |

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The U.S. Food and Drug Administration (FDA) has put a clinical hold Denali Therapeutics’ application to begin clinical testing of DNL919, an immune-modulating medication that the company is developing to treat Alzheimer’s disease.

The FDA will issue an official clinical hold letter to Denali in the next month or so, according to a company press release. Denali had been hoping to start clinical testing of DNL919 in the first half of this year.

The company said it will provide further updates “pending discussion with the FDA.”

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The news comes scarcely a month after Denali announced that Takeda Pharmaceutical Company had exercised its option to co-develop and co-commercialize DNL919 as a potential Alzheimer’s therapy, per a 2018 agreement between the two companies.

The active agent in DNL919 is an antibody that is designed to bind to a protein known as TREM2 (triggering receptor expressed on myeloid cells 2), which is expressed exclusively by cells called microglia. Mutations in the gene that codes for this protein have been linked with an increased risk of Alzheimer’s.

Microglia are the resident immune cells of the brain. They are the first line of defense in protecting delicate brain tissue from dangerous infections and play an important role in clearing out toxins and cellular debris from the brain. Dysregulated microglia are thought to play a role in the development of Alzheimer’s and other neurological diseases.

According to Denali, DNL919 is “designed to modulate TREM2 and thereby normalize microglial function,” which the company ultimately expects to have therapeutic benefits for people with Alzheimer’s.

While some antibody-based therapies have been useful for treating certain diseases, these medications generally have been difficult to use for Alzheimer’s and other brain diseases because of the blood-brain barrier (BBB). As its name implies, the BBB is a cellular divide that regulates what substances from the blood are able to cross into the brain. This helps to keep the brain free of dangerous toxins, but often stops medications from entering the brain.

DNL919 uses Denali’s Antibody Transport Vehicle (ATV) technology to overcome the BBB and deliver the therapy to brain tissue.