FDA Grants Orphan Drug Designation to Azeliragon for Glioblastoma

The FDA has granted an orphan drug designation to azeliragon (formerly TTP488) for the treatment of patients with glioblastoma, according to an announcement from Cantex Pharmaceuticals. The company licensed the drug from vTv Therapeutics Inc, which had been initially under development for Alzheimer’s disease.¹

“Receiving FDA orphan drug status for azeliragon highlights the significant unmet need for novel treatment options for patients with glioblastoma, the most common and lethal primary brain cancer,” Stephen G. Marcus, MD, chief executive officer of Cantex, said in a press release. “This designation validates our continued commitment to developing new treatment options for patients with glioblastoma, as well as for other cancers and their complications, including breast cancer, cancer chemotherapy–related cognitive decline, pancreatic cancer, and cancers such as breast and lung that have metastasized to the brain.”

Azeliragon is an orally active, small molecule antagonist of the receptor for advanced glycation endproducts (RAGE). The agent, which is administered once daily, inhibits RAGE interactions with certain ligands, including HMGB1 and S100 proteins in the glioblastoma microenvironment. By preventing interaction of RAGE with these ligands, azeliragon may inhibit glioblastoma and overcome its resistance to effective treatment.

Clinical safety data from former trials evaluating more than 2000 patients with Alzheimer’s who received up to 18 months of treatment demonstrated that azeliragon is well tolerated.²

Additionally, treatment with 5 mg/day of azeliragon delayed the time to cognitive deterioration (7-point change in ADAS-cog from baseline, log rank P =.0149). Based on these results from the phase 2b study, the registrational phase 3 STEADFAST trial (NCT02080364) was launched under a Special Protocol Assessment from FDA. However, the trial was ultimately terminated due to lack of efficacy at the 5 mg/kg dose.³

Cantex is also developing azeliragon for the treatment of other cancers poor outcomes due to with RAGE-mediated resistance and treatment-related complications.

References

1. Cantex Pharmaceuticals receives FDA orphan drug designation for azeliragon for the treatment of glioblastoma. News release. Cantex Pharmaceuticals. January 9, 2023. Accessed January 10, 2023. https://prn.to/3W10fuD
2. Burstein AH, Sabbagh M, Andrews R, et al. Development of azeliragon, an oral small molecule antagonist of the receptor for advanced glycation endproducts, for the potential slowing of loss of cognition in mild Alzheimer’s disease. J Prev Alzheimers Dis. 2018;5(2):149-154. doi:10.14283/jpad.2018.18
3. Evaluation of the efficacy and safety of azeliragon (TTP488) in patients with mild Alzheimer’s disease (STEADFAST). ClinicalTrials.gov. Updated May 7, 2021. Accessed January 10, 2023. https://clinicaltrials.gov/ct2/show/NCT02080364