Shares in vTv Therapeutics fell more than 25 percent following the company's disclosure that Part B of the STEADFAST study investigating azeliragon in people with mild Alzheimer's disease failed to meet its co-primary efficacy endpoints. Despite the setback, CEO Steve Holcombe said "we believe that azeliragon has the potential to address the pressing unmet need in Alzheimer's disease."
The STEADFAST study consists of two identical Phase III trials, dubbed Part A and B, designed to investigate the safety and efficacy of azeliragon for the treatment of patients with mild Alzheimer's disease. The studies were expected to each enrol 400 patients, although Part B was halted early after vTv reported in April that in Part A of the trial, azeliragon did not meet either co-primary efficacy endpoint, which were cognitive or functional outcomes as measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb).
The company subsequently announced that based on post-hoc analyses of data from Part A of the study, a subpopulation of patients receiving azeliragon showed significant benefit relative to placebo on ADAS-cog. According to vTv, the subpopulation consisted of participants with peak azeliragon blood plasma concentration of less than 7.5 ng/mL. The drugmaker later prespecified this patient group as the primary population prior to unblinding in Part B.
Despite top-line results from Part B showing that azeliragon failed to meet the main goals as measured by ADAS-Cog and CDR-sb, vTv said that consistent with prior findings, lower maximal plasma concentrations of the drug were associated with improvements in efficacy relative to placebo. The company added that when pooling the results of Part A and B, and comparing change from baseline at 12 months, the azeliragon subgroup, consisting of 88 patients, had a 1.8-point improvement in ADAS-cog, a 0.4 improvement in CDR-sb and a 2.3 improvement in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) relative to the 373 patients in the placebo group.
The drugmaker said that it is seeking a meeting with the FDA to propose a pathway for further development in support of regulatory approval of azeliragon. Holcombe remarked "we are eager to obtain early feedback from the FDA based on the results we have achieved and the data that we have observed associating lower plasma levels of the drug and improved efficacy."
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