Yesterday, publicly traded vTv Therapeutics announced the termination of both parts of its STEADFAST clinical study, which had been testing the small molecule azeliragon in patients with probable Alzheimer’s. According to topline data from Part A of the Phase 3 clinical trial, patients who took the drug for 18 months performed no better than those on placebo in tests of cognition and function. Though only a fraction of patients in Part B, which is identical in design, have completed 12 months on the drug, the company has terminated that trial. In a press release, vTv said it would analyze the data for trends in subgroups.
- Azeliragon shows no benefit in Phase 3 trial.
- Patients on the RAGE antagonist decline just as fast as those on placebo.
- Company halts development of the small molecule for AD.
Azeliragon blocks the receptor for advanced glycation end products (RAGE), which can cause inflammation in the brain. Because microglia and astrocytes upregulate expression of RAGE in AD, and because evidence suggested RAGE binds and mediates Aβ toxicity, researchers reasoned that blocking the receptor would be beneficial (Mar 2008 news).
TransTech Pharma discovered azeliragon, a.k.a. TTP 488, and licensed it to Pfizer, which, together with the National Institute on Aging, sponsored an 18-month trial of the antagonist back in 2007. Run by the Alzheimer’s Disease Cooperative Study, it tested daily doses of 5 mg and 20 mg given after six-day ramp-ups of 15 mg and 60 mg, respectively, in patients with mild to moderate AD. Trials of both dosing regimens were halted early for lack of efficacy (Nov 2011 conference news).
Latching onto hints of a benefit in patients with mild AD, TransTech Pharma, which would become vTv, received fast-track approval from the Food and Drug Administration to test the drug in patients with probable AD and a brain MRI consistent with that diagnosis. No other markers were used for inclusion criteria. The STEADFAST study was slated to recruit 800 participants randomized to either 5 mg/day azeliragon or placebo. Primary cognitive and functional outcome measures were the ADAS-Cog and CDR-sum of boxes, respectively.
In its press release, the company reported that treatment and placebo arms worsened by 4.4 and 3.6 points, respectively, on the ADAS-Cog, while both changed by 1.6 on the CDRsb. The ADAS-Cog differences were not statistically significant.—Tom Fagan