FDA Makes Changes to Alzheimer’s Clinical Trial Goals Amidst Recent Failures

As reported by KCCI in Kansas, Pfizer Inc. has ended funding to its Alzheimer’s programs. It reports that the company plans to invest in other research programs through venture funds, although no specifics have been released.

This appears to be a follow-up to January reporting that Pfizer was abandoning its Alzheimer’s and Parkinson’s disease programs, which would include eliminating 300 jobs from the neuroscience discovery and early development programs in Massachusetts and Connecticut. In a statement at the time, Pfizer said, “This was an exercise to re-allocate spend across our portfolio, to focus on those areas where our pipeline, and our scientific expertise, is strongest.”

It also follows a very tough week for Alzheimer’s research and development. On February 14, Merck & Company announced it was halting protocol 019, its APECS Phase III clinical trial of verubecestat (MK-8931) in Alzheimer’s disease. An external Data Monitoring Committee (eDMC) had recommended halting the trial after an interim safety analysis found the likelihood of benefits didn’t outweigh the risks.

Verubecestat is a BACE inhibitor. BACE is behind the development of beta-amyloid, which is believed to be the predominant cause of Alzheimer’s disease. The theory is that by inhibiting BACE, it will halt the development of beta-amyloid, which will prevent the disease from occurring. Later in the disease, tau proteins accumulate in the brains of Alzheimer’s patients, but that has not been as intense a focus as amyloid clearance or prevention.

Only a day later, Biogen stock dropped after the company’s chief medical officer, Al Sandrock, speaking at the Leerink Healthcare Conference, startled investors by saying the company had added 510 more patients to its clinical trial of aducanumab in Alzheimer’s disease.

Aducanumab is not a BACE inhibitor. It is an antibody for beta-amyloid, designed to clear beta-amyloid after it appears. The company indicated the expansion was made to help clear up some of the “variability” they were finding in the data. Investors, however, probably spooked by the Merck news, caused the company stock to plunge by 9.1 percent.

In a post today, Keith Speights, writing for The Motley Fool, pondered the question of whether investors should buy Biogen on the dip caused by Sandrock’s statement. Both of the earlier points were mentioned—the Merck trial and the trial expansion—but he also mentioned that Biogen recently stopped a Phase II trial of its multiple sclerosis (MS) drug Tysabri, because it was no more effective than a placebo for treating stroke.

“The bigger issues for Biogen, though,” he writes, “stem from competition for its current products. Roche’s Ocrevus presents a threat to Tecfidera and Tysabri, two of Biogen’s biggest moneymakers. Although Biogen receives royalties from sales of Ocrevus, the negatives of lost market share for its existing products outweigh the positives from those royalties.”

It is also facing competition for its MS drug Tecfidera from Celgene’s ozanimod, and Avexis’s potential new drug for spinal muscular atrophy (SMA). Biogen’s Spinraza for SMA was approved in early 2017.

Despite the recent dismal news regarding Alzheimer’s drug development, the U.S. Food and Drug Administration (FDA) recently proposed new guidelines for developing drugs for the disease. The goal is lowering the clinical study goals. The strategy is part of the agency’s efforts to expand access to treatment options for many diseases, and hints that it might consider an accelerated approval process.