President Joe Biden recently nominated former FDA Commissioner Robert Califf, M.D., to run the agency once more, ending nearly a year of temporary leadership under Acting Commissioner Janet Woodcock, M.D. One insider says that Califf might look to reform and improve the accelerated approval pathway following the controversial Aduhelm (aducanumab) approval earlier this year.
Califf previously led the FDA during the Obama administration, running the agency for roughly the last two years of Obama’s term. Califf advocates for using “real-world evidence” in addition to clinical trial data in medical approvals. Aduhelm, an Alzheimer’s drug, was approved without such data, though studies of the drug relying on real-world evidence — which takes into account electronic medical record and insurance claims data — are underway. During Califf’s initial tenure, Sarepta Therapeutics’ eteplirsen, a muscular dystrophy drug, also earned accelerated approval despite a large outcry from medical researchers.
Critics Raise Ethics Concerns
After leaving government, Califf led Google parent company Alphabet Inc.’s medical division. Before serving in government, Califf administered clinical trials on behalf of pharmaceutical manufacturers at Duke University. Because of that work, members of Congress including Sens. Bernie Sanders (I-Vt.) and Ed Markey (D-Mass.) expressed concerns during Califf’s initial nomination review in 2015 that he might have conflicts of interest. Those criticisms have come up again — Califf received compensation from pharma companies as a board member in recent years — but Califf seems likely to be approved by the Senate through a bipartisan vote once again, despite the objections of Democratic Sens. Joe Manchin and Richard Blumenthal.
Speedy Approvals May Be Reformed
Kelly George, Ph.D., an associate principal at Avalere Health, tells AIS Health, a division of MMIT, that the accelerated approval process does meet an important need despite recent controversies.
As a physician, Califf “understands the concept of what it means to have patients with unmet medical needs,” George explains. “What it means to wait to get all the data sets, means that there are patients that could potentially benefit [before approval], but can’t because you’re still waiting for 100% [of clinical trial] data. That’s where the accelerated approval comes in — what are these types of drugs that are looking at really long timelines?”
“The point of accelerated approval is being able to potentially meet patients’ needs while we’re gathering more data,” George continues. “If there’s a suggestion of efficacy, there’s a suggestion of a patient benefit, we’d rather have something on the market than nothing.”
The accelerated approval process was designed in the 1990s, after largely LGBTQ+ activists, such as ACT UP, pushed the FDA to grant HIV/AIDS patients access to experimental therapies.
“The whole point is, we don’t know a tremendous amount about [accelerated approval] drugs,” George explains. “That doesn’t necessarily mean they don’t potentially have benefit. Aduhelm ended up in a rather controversial space.”
Aduhelm did meet some clinical standards, George says, “but people are still parsing out what [Aduhelm] means for the patient in the end.”
“There’s certainly a number of conversations about improving the process,” George adds. “Instead of products continuing to stay in the market until FDA does something, you could switch the burden and say the sponsor [company] automatically loses market access at a certain point, unless FDA does something. There’s also a MEDPAC proposal where you have a different rebate and pricing system for products in that pathway.”
Can Califf Move the Agency Forward?
“What Califf does in this space is he brings expertise in both real-world evidence and clinical trials…those are two fantastic ways to get data on a drug more quickly and efficiently,” George continues. “You can do real-world evidence, once we have our feet on the ground in that space — presumably you can do it cheaper and quicker.”
George believes that Califf’s ability to “move the agency forward” in real-world evidence “is fantastic. The thing about real-world evidence, which may not be applicable to Califf, is it pulls the power away from sponsors and into…stakeholders’ hands.”
If a clinical trial is the only acceptable standard of evidence, “you went back and looked at the clinical trails that the sponsor ran. And that was it. The sponsor ran trials…they published what they wanted to publish.”
George says that the real-world evidence trend allows “collaborations like ICER. They are getting together and saying, let’s go look at drugs that have already been on the market for years, and do real-world evidence studies and see if those studies come up with the same types of efficacy as the clinical trials way back when. So that’s no longer the sponsor controlling the data — that’s the third party who [manages value or] pricing and [coverage] decisions based a whole new set of data.”
Contact George via Isabella Paladino at Isabella.firstname.lastname@example.org.
This story was reprinted from AIS Health’s biweekly publication RADAR on Drug Benefits.