- The Alzheimer's disease space saw another late-stage drug failure on Monday as vTv Therapeutics Inc. announced its lead candidate didn't outperform placebo in Part A of the biotech's STEADFAST program.
- STEADFAST consists of a pair of identical Phase 3 studies, each enrolling 400 participants and evaluating the efficacy of vTv's azeliragon through two cognitive tests. Results from the first study showed patients treated with the experimental drug experienced the same cognitive decline as the placebo group on one of the tests, and a worse decline on the other.
- Shares of vTv fell nearly 70% on the news, to trade at $1.01 apiece by market's open Tuesday. In a statement, the High Point, North Carolina-based company said it is discontinuing all clinical investigations of azeliragon, including Part B of STEADFAST.
Alzheimer's disease is historically difficult to treat, a trend underscored in the last six months. The outlook for Biogen Inc. and Eisai Co. Ltd.'s BAN2401 dimmed in November after the drug failed to meet the primary endpoint of a Phase 2 trial. And in February, Merck & Co. scrapped development of its beta-secretase 1 inhibitor verubecestat after a Data Monitoring Committee said the drug was unlikely to have a favorable risk/benefit profile in a Phase 3 trial.
The setbacks have whittled down an already short list of Alzheimer's candidates in later-stage clinical development. Now, most of the industry's hopes are hinged on Biogen's aducanumab, though even that drug has caused concerns.
A day after Merck's announcement, Biogen said it would increase enrollment in a pair of Phase 3 studies evaluating aducanumab because of "variability" on the primary endpoint. The wording spooked investors, leading to a nearly 7% drop in the big biotech's stock.
Analysts maintained a more tepid response to Biogen's disclosure. But given the series of failures in Alzheimer's, even the more positive views on aducanumab peg the drug at a 65% chance of success.
Data from those late-stage studies likely won't read out until late-2019 or early 2020. And with Merck's and vTv's drugs scrapped, there's not too much to look forward to in the near-term.
Eisai Co. Ltd. and Biogen Inc. have their own beta-secretase enzyme inhibitor, E2609, in Phase 3 testing. A Phase 2 dose-finding study of the drug is set to complete this month. Roche AG, meanwhile, expects a primary completion date in November for a Phase 3 study of gantenerumab, an amyloid beta inhibitor.
Against a steep stock drop, vTv said it will continue to assess the data coming from the Part A and Part B studies.
So far, the company has seen that azeliragon-treat patients in Part A had a 4.4 point decline from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale and a 1.6 point decline from baseline in the Clinical Dementia Rating Scale Sum of Boxes. Patients in the placebo group demonstrated a 3.3 point decline and 1.6 point decline, respectively, in the tests.