Califf on Tweaking Accelerated Approvals, No Big Revamp
FDA commissioner Robert Califf does not think a total revamp of the drug accelerated approval program is needed in response to criticism that followed a number of drug indications being withdrawn because companies were unable to generate confirmatory effectiveness data. Delivering the commissioner’s address at the Food and Drug Law Institute’s (FDLI) annual meeting 6/14 in Washington, DC, Califf told the audience he is still a fan of the program due to his personal experience with his mother gaining an extra three to four years of living with multiple myeloma after taking an accelerated approval drug.
Califf acknowledged that the program’s biggest fault is probably companies being “too focused on just the acceleration and not enough on the evidence that’s needed to fill in that gap between when approval occurs and when you need the definitive evidence that the treatment fulfills its promise.” He said he supports the user fee legislation moving through Congress that includes certain provisions and “very good approaches to dealing with this,” such as requiring sponsors to have a confirmatory trial underway at the time of approval. He is also backing additional authorities being granted the agency to more efficiently deal with companies who don’t fulfill their confirmatory evidence requirements.
Califf was asked to comment on the recent CMS National Coverage Determination on Medicare coverage for only FDA traditionally approved monoclonal antibodies, and not therapies that have been granted accelerated approval, that target amyloid for treating Alzheimer’s disease. The coverage determination was a significant blow to Biogen’s controversial accelerated approval of Aduhelm (aducanumab), and drug development watchers warned that it could chill development of other potential accelerated approval products, with many perceiving CMS as second guessing an FDA approval decision.
“I don't see this as second guessing at all, because we have different missions,” Califf told the FDLI audience. FDA has standards it follows to reach an approval decision, and CMS has to decide about coverage of a product using a different set of criteria, he said. “One good thing that’s occurred because of those decisions is that we’re working much more closely with CMS now to think these through,” he said. Califf described the past working relationship as being similar to a relay race where FDA runs a lap and then drops the baton, but CMS has got to figure out where it is and pick it up and start all over again. “We really ought to be running side by side in the last phase to make sure that CMS has the data it needs during that transition,” he said.
Additionally, Califf was asked about what is critically important to fix now so that FDA is prepared for the next pandemic. He identified supply chain problems and the U.S. evidence generation system needing work. Califf said there is “no technical reason why the critical supply chains are not digitally integrated so that the system can be stress-tested, preemptive action can be taken, and reaction to problems can be swift. The authority granted to us by Congress in this regard is very limited. Consequently, we often find ourselves reacting to shortages after the fact in every single industry—for example, there were over 300 drug shortages last year and significant restriction of contrast agents affecting my specialty of cardiology.”
A big problem, he continued, is that “each firm manages its own supply chains, but there is no composite view that enables anyone to understand the complete picture. When one firm, as in the case of infant formula, goes down, the ability to adapt is impaired. What we need is a national system that allows some entity, perhaps the FDA, to see what’s going on, make sure the supply is getting where it needs to go, do stress testing, and anticipate where there may be shortages. I am a fan of the benefits of the market, but when it comes to health, a market failure can lead to death and loss of dignity and physical function for those affected. So, the system should monitor, but not intervene except when necessary to prevent harm.”
In order to do this, according to Califf, more transparency on the information manufacturers have about each of their individual supply chains is needed. “The industry has considered this proprietary and has fought prior efforts for the government to gain access,” he said. “This needs to change, so that we can prevent shortages from happening rather than waiting until they happen when it is often too late to prevent serious harm.”
To view Califf's prepared remarks, which include his priority focus areas, click here.