In the biomedical world, perhaps the biggest question looming over President Donald Trump’s upcoming pick for Food and Drug Administration commissioner is how drastically that person will help roll back FDA regulations.
Trump said at last week’s meeting in Washington D.C., with pharmaceutical executives that he wanted to slash FDA rules by 75 to 80 percent—“at a level no one has seen before”—while still promising “tremendous protection for the people.”
Taken at face value, those pledges would seem to benefit one group that has often fought red tape: patients and their advocates who feel regulatory strictures keep them from getting new, potentially life-saving drugs. They pressed hard for last year’s 21st Century Cures Act and its omnibus of looser regulations, guaranteed research funding, and mandates for the FDA to integrate patient feedback into its decisions.
Patient groups cheered when Barack Obama signed the Cures Act into law at the end of his presidency. Their growing impact on funding and regulatory decisions spurred this comment from former FDA commissioner Robert Califf at a conference just after his recent resignation: “If I had a disease with an ineffective advocacy group, I’d be worried right now.”
But as “patient-centric” gains traction as a Washington buzzword, many patient advocates say they are wary of what might be coming. “While this current climate of deregulation may seem popular, the potential harm and risk for patients is too great when considering our past and the important part the FDA plays in patient safety,” says Kimberly Haugstad, president and CEO of the nonprofit Hemophilia Federation of America. The mother of a boy with hemophilia, Haugstad cites thousands of hemophiliacs dying from HIV after receiving tainted blood three decades ago as “one of the largest regulatory failures in recent history.”
Adding to the misgivings are the known views, often stridently anti-FDA, of some of the potential commissioner choices who have emerged, matching a pattern of the new administration nominating critics of federal agencies to run those same agencies.
Barbara Handelin, CEO of nonprofit BioPontis Alliance for Rare Diseases in Raleigh, NC, says that an investor taking the helm—three of the names floated are active in private equity—“would once again be choosing the fox to guard the hen house.”
She says she wants to see a commissioner who can balance scientific rigor, encouragement of industry innovation, respect for drug firms’ business goals, and independence from industry at the same time. None of the current names meet those criteria, Handelin says.
An official nominee is likely to emerge soon, now that the Senate has confirmed Tom Price to run the Department of Health and Human Services. Price, who will oversee the FDA, the Medicare and Medicaid insurance programs, and other health-related agencies, won the seat despite strong Democrat objections over his healthcare stock trades as a member of Congress.
“RADICAL” AND “RAMP IT UP FASTER”
The rumored candidate whose views have caused the most concern is Jim O’Neill, a hedge fund manager and associate of Trump supporter Peter Thiel. O’Neill held a position in the George W. Bush administration at the HHS. When his name emerged in December, Bloomberg News found a recording of his appearance at a conference, during which he said the FDA should only evaluate drugs for safety. Whether they work or not—the standard of “efficacy,” in FDA-speak—should be determined once they are on the market, he said.
Hank Greely, the director of Stanford University’s Center for the Law and Biosciences, says that “radical” view of bringing drugs to market faster probably isn’t realistic—not the least of which because it would require Congress to change a key FDA statute. “It’s a nice libertarian talking point, but not many people—not insurers, not the drug industry, not doctors—really want it,” Greely says.
“It’s critically important to demonstrate effectiveness,” says Tim Coetzee, chief advocacy, services and research officer at the nonprofit National Multiple Sclerosis Society in New York. Many times an MS treatment has been “anecdotally beneficial,” Coetzee says, but getting to clinical trials didn’t change anyone’s health for the better.
As for a more moderate, “ramp it up faster” approach to drug evaluation, “it seems like it’s already faster,” says Greely. The perception of the FDA as a bottleneck changed under President Obama’s first FDA commissioner, Margaret “Peggy” Hamburg, who oversaw new programs to streamline reviews and—of no small importance—helped boost the agency’s budget. (Part of that increase went toward FDA’s new tobacco regulation authority.)
Groups with a mission to speed up life-saving drugs to patients agree. “The FDA is the gold standard in the world in terms of reviews,” says Faster Cures executive director Margaret Anderson. “We’re not hearing anyone interested in lowering the bar.”
Anderson referred to a Faster Cures survey late last year of 150 entities from the biomedical community, including drug companies and patient advocate groups. Everyone who has to work with the agency has suggestions for improvements, many of which the FDA has cautiously begun to explore. But of greater concern, Anderson says, is that the agency be better staffed, fully funded, and that the law to allow it to fund its drug-evaluation work—the Prescription Drug User Fee Act (PDUFA)—be reauthorized this year without delays. Nearly everyone interviewed for this story echoed those same concerns. (Republicans reportedly have set a June PDUFA deadline, but there are reasons to worry about delays.)
Changes under Hamburg and her successor Califf have allowed drugs to come to market with abbreviated testing for efficacy as long as post-approval studies continue to show good results. For example, the successful cancer immunotherapy pembrolizumab (Keytruda), famous for treating President Jimmy Carter’s skin cancer, was first approved in 2014 based on a 173-person trial that compared the drug to historical standards, not to the then-current standard of care. Pembrolizumab has since been approved for certain patients with lung and head-and-neck cancer, as well.
These so-called conditional approvals are not without controversy. Last year, senior FDA officers overruled agency staff to approve eteplirsen (Exondys 51), a drug to treat a subset of patients with the rare genetic disease Duchenne muscular dystrophy. There was no direct evidence of efficacy, but the FDA’s top drug evaluator, Janet Woodcock, gave a green light on Sept. 19 because the data were “reasonably likely to predict clinical benefit” for patients.
Duchenne patient groups, which had exerted intense pressure on politicians and FDA staff, hailed the decision. But others saw it as a slippery slope toward more approvals based on flimsy data, not to mention more encouragement of drug companies to fund patient groups. Consumer watchdog Public Citizen, a critic of the ties between the two, published a report last year on the alignment of pharma funding with patient groups’ lobbying against Medicare changes.
Rare disease patient advocates, working with patients who often don’t have an approved drug for their condition, are very vocal. But what about those who campaign for patients with much more common diseases? Alzheimer’s disease is already a massive health and financial burden and will keep growing as the population ages. Other than a few drugs that temporarily slow cognitive decline for some patients, nothing to treat Alzheimer’s has ever received the FDA’s blessing. The failure rate in clinical trials was nearly 100 percent when this study was published in 2014, and more failures have accrued since then.
But a patient advocate says less regulation wouldn’t necessarily help. “We haven’t had any experience that the FDA is being too tight or over-regulating Alzheimer’s drugs,” says George Vradenburg, chairman of US Against Alzheimer’s. “They’re willing, ready, and able to evaluate drugs that are successful in clinical trials. But they haven’t received any.”
Could the agency make changes to help more Alzheimer’s drugs get into and through clinical trials? The process is daunting because the disease takes so long to advance. Drug makers would love to use a biological signal that shows a drug is working—a short cut, in effect, around long trials that have to show better health outcomes. These signals, known as surrogate endpoints, are often acceptable to FDA reviewers in other fields. One classic example is the use of viral load—the amount of virus in a blood sample—to assess a drug’s effect on HIV infection. More recently, the FDA approved two cardiovascular drugs because they dramatically lowered cholesterol in clinical trials, even though the studies were not designed to determine whether the drugs made people healthier.
(The eteplirsen approval was also based on a surrogate endpoint: the amount of an important muscle-protecting protein that patients were able to produce after taking the drug.)
Getting FDA to accept a surrogate endpoint is not as easy as everyone would like: Coetzee of the National MS Society says trying to qualify a surrogate endpoint is “almost as challenging as getting a new drug approved.” For example, Coetzee would like to see the FDA be more flexible to allow brain changes, measured with magnetic resonance imaging, stand in for more conventional measures when studying previously approved MS drugs in children.
In Alzheimer’s, however, the underlying biology remains too mysterious to pinpoint a surrogate. Vradenburg says he’s confident the agency is open to using one “as long as the evidence is there. But the evidence for predictability isn’t there yet.”
TRUMP GIVES NOD TO “RIGHT TO TRY”
A Trump-led FDA could also broaden “right to try” rules that give desperate patients who aren’t enrolled in clinical trials access to drugs that are still experimental. Laws are already on the books in 33 states. In his pharma meeting last week, Trump complained that FDA was denying “terminal” patients such access. But the agency already has a program to approve one-off requests for compassionate use, as it is often called.
Compassionate use protocols might need tweaks, like less paperwork for doctors, says Stanford’s Greely, but FDA is not the bottleneck. Drug companies are not required to provide their experimental drugs outside of clinical trials. (For several stories of people battling for compassionate use access and the many reasons drug makers are reluctant to grant it, see this 2014 CNBC story.)
Handelin of BioPontis, a rare-disease drug developer that uses patient input to steer work, suggests financial encouragement for companies to provide experimental drugs for compassionate use. The Alzheimer’s advocate Vradenburg says the agency needs to get out in front with updated rules, because the day will come—such as with an Alzheimer’s treatment that in early trials stops or reverses the progression of the disease—“when there will be overwhelming demand for ‘right to try.'”
Vradenburg is cautious about the risks. A patient advocate shouldn’t just take “the popular position,” he says.
With more changes coming to the FDA—whatever one might think about them—everyone, including advocates, will in coming months or years likely find themselves reassessing many positions.