The so-called 21st Century Cures Act, now making its way through Congress, is designed to speed up the FDA review process for potentially lifesaving medicines by encouraging approvals based on midstage data. But a new case study takes a look at what might have happened if a trio of once-promising Alzheimer's drugs had made it to market before their eventual Phase III failures, painting a grim picture of the bill's potential.
Writing in the BMJ, fellows at the National Center for Health Research isolated Eli Lilly's ($LLY) semagacestat, Pfizer's ($PFE) latrepirdine and Johnson & Johnson's ($JNJ) bapineuzumab, three treatments for Alzheimer's whose Phase II results suggested they could improve cognition for sufferers of the memory-destroying disease and generate blockbuster sales in the process. Each eventually flamed out in Phase III, with semagacestat running into serious safety risks, latrepirdine coming up short on efficacy and bapineuzumab failing in a huge trial with more than 4,000 volunteers.
But what if 21st Century Cures had been on the books? As the authors point out, the bill encourages approving drugs based on Phase II data and surrogate endpoints and thus would have cleared the way for semagacestat and bapineuzumab to win approval based on their ability to remove buildups of plaques in the brain years before they had to demonstrate any effect on cognition in Phase III. And latrepirdine could have made its way to market based on promising midstage results of its own.
Each drug, at its most promising, was about four years away from completing Phase III. And the National Center for Health Research estimates each would have brought in more than $7 billion over that period had it been approved, money wasted on therapies with no cognitive benefit and, in one case, serious safety concerns.
The most alarming example is semagacestat, which Lilly and partner Elan pulled out of Phase III after discovering that patients in the treatment arm were 5 times more likely to develop skin cancer. Had the drug won early approval, the normal cognitive decline tied to Alzheimer's would have made it difficult for physicians to deduce that semagacestat wasn't working, the authors write, and it's unlikely anyone would have ferreted out the treatment's ties to cancer until the completion of a postmarketing study years later.
The BMJ study is hardly the first criticism 21st Century Cures has faced. The bill, which passed the House in July, has drawn ire from academics and public health advocates who worry it goes a step too far in speeding the review process. The proposal includes provisions that would allow the FDA to approve new antibiotics based on preclinical results and data from small human trials, and it encourages a broader embrace of surrogate endpoints in drug evaluations, urging the agency to OK treatments based on what is effectively secondhand evidence.
As the editorial boards of The New York Times and The New England Journal of Medicine have pointed out in their rebukes of 21st Century Cures, the FDA already has the fastest approval process in the world, and about one-third of all new drugs are cleared on just one late-stage study. With new programs like priority review and breakthrough therapy designations, the FDA is consistently shortening its standard 10-month vetting process to as few as 6 months. Speeding that up, critics fear, could put patients at risk.
- read the study