FDA Grants Orphan Drug Status to BioXcel’s BXCL701 as Potential AML Treatment

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to BXCL701, one of BioXcel Therapeutics’ lead immunotherapies for the treatment of acute myeloid leukemia (AML).

Orphan drug status is given to investigative treatments for rare diseases, defined in the U.S. as disorders that affect fewer than 200,000 people. The designation comes with certain benefits, including financial incentives for therapy development and commercialization, U.S. market exclusivity for a period of seven years following approval, FDA support for clinical studies, and special fee exemptions and reductions.

“We believe that receiving the third ODD [orphan drug designation] for BXCL701 validates our commitment to transforming drug development in oncology, including orphan indications. We are extremely excited to evaluate BXCL701’s potential as a therapeutic option for AML,” Chetan D. Lathia, BioXcel’s senior vice president and head of translational medicine, clinical pharmacology and regulatory affairs, said in a press release. BXCL701 also is in development as a treatment for a rare form of prostate cancer, and for pancreatic cancer in combination with other immuno-oncology agents.

BXCL701 is an investigational, first-in-class, oral, small molecule that strongly inhibits the activity of dipeptidyl dipeptidases 8 (DPP8) and 9 (DPP9). DPP8 and DPP9 are two enzymes that regulate the body’s immune response, as well as the growth and migration of cancer cells.

By inhibiting the activity of both enzymes, BXCL701 promotes the activation of macrophages — immune cells responsible for removing dead cells and debris from tissues. At the same time, BXCL701 triggers a highly inflammatory form of a programmed cell death, known as pyroptosis, against certain types of cells.

BioXcel has been exploring the effectiveness of BXCL701, and its highly inflammatory mechanism of action, to treat solid cancers, including pancreatic and prostate cancer.

However, a more recent study, published in Nature Medicine, has demonstrated that pyroptosis triggered by DPP8/9 inhibitors can eliminate AML cells directly. That places AML as a new potential indication for BXCL701.

“We … show that DPP8/9 inhibitors induce pyroptosis in the majority of human acute myeloid leukemia (AML) cell lines and primary AML samples, but not in cells from many other lineages, and that these inhibitors inhibit human AML progression in mouse models,” the researchers said.

If confirmed, the new findings may open the door to the expansion of BXCL701’s current therapeutic indications, underscoring its versatility to trigger strong immune responses against solid cancers and to destroy AML cancer cells directly.

“AML is an aggressive form of cancer, originating in the myeloid line of blood cells. For patients who don’t respond adequately to induction therapy or who quickly relapse (about 50% of all patients), outcomes can be particularly poor. Newer, more effective therapeutic options are therefore needed for this indication,” said Vincent O’Neill, MD, senior vice president and chief medical officer of BioXcel.

“BXCL701 has been observed to directly attack and kill AML cells in multiple preclinical studies, corroborating our belief that BXCL701 presents an opportunity to address this rare and deadly disease,” he said.

BioXcel plans to further investigate BXCL701 either as a single agent or in combination with other therapies for patients with high unmet medical needs.

“We believe that an active agent that is orally available offers important advantages in the clinical setting, and could combine well with other oral drugs, potentially providing patients with an all oral combination option,” O’Neill added. “We look forward to exploring BXCL701 as a therapeutic option for AML as we finalize development plans and continue discussions with a number of leading academic centers.”