FDA is Green-Lighting Drugs at Breakneck Speed and Raising Alarm

The U.S. is approving new drugs so fast that companies are now preparing for a green light months in advance of the scheduled decision date, a pace that’s helping patients with rare or untreatable diseases but raising alarm among consumer advocates.

Global Blood Therapeutics Inc., maker of a new sickle cell disease drug called Oxbryta, built a booth to showcase the medicine at the annual meeting of the American Society of Hematology that begins this weekend — even though the Food and Drug Administration’s scheduled approval date was in March.

The move paid off: Oxbryta was given the go-ahead by the FDA on Nov. 25, almost three months ahead of schedule, and the branded booth will make its debut at the ASH conference in Orlando, Florida, on Saturday.

“It’s very much a change,” said Alethia Young, a biotechnology analyst at Cantor Fitzgerald in New York. “It has happened over the past five years, and it’s probably here to stay. In areas of high unmet need, FDA seems to be committed to getting medicines to these people as fast as possible.”

Oxbryta’s approval added to a growing number of breakthrough products that have beaten their FDA deadlines by weeks and sometimes months. For normal medicines, the agency typically has 10 months to issue a ruling. For those with exceptional benefits, or that treat conditions with few existing therapies, it offers a priority review that takes just six months. From mid-October to mid-November, the agency approved five medicines in as little as eight weeks.

The shift is emerging as the FDA is approving new drugs at a record pace, and breakthroughs in biotechnology and genetics are enabling drug companies and their scientists to provide more specific data to federal regulators.

“It isn’t that we changed our policies and are saying we are going to approve drugs faster,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, who joined the agency under President Ronald Reagan. “The difference now is we are going to see more of those because of the science. If there are people out there with no options and they have terrible diseases, we are going to get those drugs to them as fast as feasible.”

But even as drugmakers, investors and patients cheer on the agency’s pace, patient-safety advocates argue that speed comes at a price. Studies show medicines approved on a faster time line are more likely to have safety problems emerge after they become broadly available, while other treatments offer fewer benefits than anticipated.

While the Trump administration has focused on reducing regulation across the U.S., the FDA’s new-found speed had its genesis more than a quarter-century ago. Drugmakers agreed to pay the agency user fees in return for firm deadlines after years of wild guesses. Congress and the FDA layered on programs providing incentives for drug developers to craft products for patient groups with critical unmet needs, especially for rare conditions.

It’s not just speed. The FDA also is approving more drugs, hitting a record 59 new therapies in 2018. Almost three-fourths received a priority review. That, combined with more efficient data collection, is responsible for the faster FDA action, said Aaron Kesselheim, a professor at Harvard Medical School. Companies are also communicating earlier and more often with the agency, which can head off issues at preliminary stages and help them get products through on the first attempt, he said.

Vertex Pharmaceuticals Inc.’s Trikafta, a triple combination of drugs to treat cystic fibrosis, won FDA approval in October, five months earlier than expected. Investors dubbed it an early Christmas gift from the FDA.

Clearance for Novartis AG’s Adakveo, another new medication for sickle cell disease, came in November. It was 62 days ahead of the FDA’s deadline, known as the PDUFA date. BeiGene Ltd.’s Brukinsa was approved three months ahead of schedule for mantle cell lymphoma.

“These are all rare diseases, genetic conditions, being treated with new and exciting technology,” said Ira Loss, who tracks the internal workings of the FDA for Washington Analysis. “If you have all the data, why wait six more months? You’re talking about people’s lives here.”

Enrolling patients in clinical trials for rare diseases can be challenging, and proponents are eager to jump on the first signs of a response, especially if there are few or no other treatments. But acting fast, based on data from a small number of patients treated for a short period, can miss some serious drawbacks.

“We’re allowing drugs come to market sooner, faster without having sufficient information about their safety,” said Michael Carome, health research group director at the consumer advocacy group Public Citizen. “Over the last few decades the FDA’s standards for approving drugs have weakened, which has led to faster drug approval.”

It’s also led to more concerns emerging after drugs are on the market, he said.

Take Makena, a treatment from AMAG Pharmaceutical Inc. that was supposed to delay preterm births. Public Citizen has been lobbying against the injectable medicine since data failed to show it works. The catch? The results came out years after the drug was already on the market.

“There’s evidence that when drugs are approved on a faster time line, they are more likely to be associated with post-approval changes to their safety-related labeling,” said Kesselheim, the Harvard professor. Drugs that get an expedited approval are 48% more likely to subsequently get an update to their boxed warning — the FDA’s most severe — or contraindications that restrict their use than those that go the traditional route, according to one study that he helped conduct.

Other research has tied faster drug approvals to increased boxed warnings, the most severe form, as well as market withdrawals.

But that alone isn’t a reason to pull back, he said.

“That increased risk that you take by approving drugs quickly is reasonable — if that drug is a very promising drug that meets an unmet medical need for a serious or life-threatening condition,” Kesselheim said.

Finding flaws after a drug is on the market may be a sign that the system is working, the FDA’s Woodcock said.

“We would expect every once in a while that we would be wrong,” with an accelerated approval, she said. “Otherwise, we aren’t taking any chances, we are still making them wait too long to get their hands on this therapy that will extend their lives.”

There are more than three dozen medicines waiting in the wings. They include Seattle Genetics Inc.’ cancer drug enfortumab vedotin, Merck & Co.’s Ebola vaccine V920 and the peanut allergy medicine Palforzia from Aimmune Therapeutics Inc. Esperion Therapeutics Inc. is waiting on decisions for its cholesterol-lowering pills.

“You can’t assume every drug that has a breakthrough designation will get approved early,” Young said. “You never know when a delay will pop up.”

But many companies are taking the gamble.

“We did a lot of things at risk,” including building the branded booth for Oxbryta, said Global Blood Chief Executive Officer Ted Love, “Every day people are dying from this disease. I think the FDA recognized that ASH was a great opportunity for physicians to come to our booth and see the abstracts and presentations and know the drug is fully available.”