There’s been a lot of talk in biotech lately about the need for reforms at the FDA, to make it run faster and more predictably. One idea is taking shape in a bill starting to move through Congress. And at least at first glance, it looks like it’s based on good common sense.
The idea is to make it possible for experimental drugs for rare, life-threatening diseases get to the market faster, by expanding the FDA’s “Accelerated Approval” pathway. A bill called “FAST” that seeks to make this happen was introduced last week and discussed at a public hearing held by the House Energy & Commerce Committee’s Subcommittee on Health.
Here’s the background. Twenty years have gone by since AIDS activists scored a historic victory by getting the FDA to allow for “Accelerated Approval” of experimental drugs that might save lives. That deal enabled patients who were dying of AIDS to get faster access to drugs that otherwise would have been bottled up for years in clinical trials, as researchers tried to gather proof that they helped people live longer than placebos. In backing away from that demanding stance for medical evidence, the FDA agreed to accept certain “surrogate endpoints.” Those measurements—things like viral suppression in AIDS patients—might suggest at an earlier stage of development whether a drug is working and worth delivering to more patients.
In exchange for an earlier-than-usual drug approval on a thinner body of evidence, companies were supposed to follow through on gathering more hard data on things like how long patients were living. And if later evidence emerged that suggested the early indicators were misleading, and the new drug wasn’t actually as safe or effective as first believed, then the FDA would have the right to revoke the “accelerated approval.” For many years since, this same regulatory path has helped make it possible to bring cancer drugs to the market faster than they otherwise would. (There have been problems with this approach, but more on that in a minute.)
The key idea in this FAST bill is that this same regulatory template should be extended to many more “serious or life-threatening” diseases. The logic here is sound: If we can use surrogate endpoints to measure the effectiveness of HIV and cancer drugs, the same idea can be applied to rare diseases like beta-thalassemia or Huntington’s disease. Boosters of the legislation like to claim that as understanding of biology advances, and we learn more about biomarkers in the blood that are leading indicators of disease, we ought to take advantage of them to speed up drug development.
“Why just limit it to HIV and cancer?” says John Maraganore, the CEO of Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: [[ticker:ALNY]]), who testified before the House committee last week. “I think it’s important to get medicines to patients faster while retaining the safety and efficacy standards we rely on.”
Of course, Maraganore acknowledges his company “has a dog in this hunt.” Alnylam is developing treatments for rare diseases like TTR amyloidosis, Huntington’s, and hemophilia that could all end up benefitting from a faster regulatory approach. It’s hard to quantify the difference this bill could make for Alnylam, or any other company competing in those fields, because every disease, and its surrogate endpoint of progress, is going to be a different. But speaking generally, if investors have a choice of investing in a clinical trial program that will take seven years and $50 million to get the data needed for FDA approval, or one for the same drug that requires three years and $20 million of investment, which clinical trial plan do you think they’d rather back?
The investment concern is a real one. Without a more aggressive push for accelerated approvals, the overall pipeline of drug candidates could dry up in a hurry. As Maraganore pointed out in his testimony, a survey by the National Venture Capital Association last fall said that 39 percent of VCs plan to decrease their investments in cancer drugs over the next three years. That’s in large part, he said, because “there appears to be a fundamental re-evaluation” of cancer drug approval standards, which has injected a lot of uncertainty into how much time, money, and data it will take to win an FDA approval.
There are potentially negative consequences if accelerated approval goes too far. There are going to be questions about how “serious or life-threatening” diseases get defined. Is diabetes in this category, in need of shorter regulatory pathways? I think most people would say diabetes is a serious disease, but what about enlarged prostate?
Companies, once they get accelerated approvals, tend to lose
