By Robert Langreth, Fiona Rutherford and Tanaz Meghjani
One ALS drug made $400 million in sales for its maker. It doesn’t work. A cancer treatment brought in $500 million. That one turned out to have no effect on survival. A blood cancer medication made nearly $850 million before being withdrawn for two of its uses. That drug had been linked to patient deaths years prior.All of them were allowed to be sold to Americans because of the US Food and Drug Administration’s drive to get new drugs to patients quickly — sometimes even before they’re done testing. The agency has been under pressure to move faster, a dynamic that has roots in the AIDS crisis when patients were dying while waiting for new medications. But in the years since, it has evolved into an approval process that critics say is driving confusion and could be putting people at risk.
Drug companies are profiting, though. Since 2014, they’ve made at least $3.6 billion in global sales of medications that have either later been shown to be ineffective or had most or all of their uses withdrawn in the US, according to data compiled by Bloomberg.
“We get drugs faster and faster and know less and less about them and pay more and more,” says Yale University public health professor Gregg Gonsalves, a former AIDS activist who was part of a group that urged the FDA to get quicker — but also more rigorous — in the 1990s. Patient groups that are now pushing for speedy approvals took the wrong lessons from the HIV crisis, he said. “The idea is not to have more drugs. It is to have drugs that work.”
There are a number of ways a drug company can get its treatment to patients faster: There’s the “priority review” pathway, then “fast track,” “accelerated approval” and “breakthrough therapy.” Companies can also use vouchers to ensure speedier reviews for drugs that wouldn’t normally qualify. Bloomberg’s data analysis showed that the majority of new drugs in the US are approved through one or more of these sped-up pathways. Last year two thirds of all new drugs reached the market this way.
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Amylyx is how taking its drug off the market — after reaping $400 million in sales from it. Decades ago, the FDA reviewers weren’t very flexible and drugs sometimes languished for years as the agency demanded more data.
“Now they’ve gone so far in the opposite extreme direction, sometimes approving things where there’s literally no evidence except wishful thinking,” says Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank. The FDA’s Duvall-Jones said the agency only approves drugs if there is “substantial evidence” they work and the benefits outweigh the risks.
In theory, sped-up approval programs are designed for the most promising drugs that address some of the most crucial medical needs. In practice, the drug industry has found ways to expand use of these pathways beyond the relatively narrow uses for which they were originally envisioned. That may be because of pressure on the FDA from patients and their loved ones, who often join forces through nonprofits that make getting drugs approved quickly part of their mission.
The ALS Association, for example, said in its annual report that it “led a campaign to encourage the FDA to act with urgency and flexibility” to get Amylyx’s drug to patients. After Amylyx’s drug failed in the larger study, the ALS Association put out a statement expressing disappointment and noting that they had supported the early approval because the drug appeared safe and patients were “willing to take the risk if it turned out to be ineffective.”
Additional Approvals
One of the issues with the FDA letting a drug onto the market quickly is that it can open the door for similar drugs to be approved, too. That’s what happened with a group of blood cancer drugs. Gilead Sciences Inc.’s Zydelig was approved in 2014 through sped-up pathways for two types of lymphoma. But within two years, the company halted multiple studies of the drug due to serious side effects and deaths of patients in trials. The FDA put out safety warnings, yet in the years after, the agency continued to grant sped-up approvals for a number of similar drugs.
One of those was TG Therapeutics Inc.’s blood cancer pill Ukoniq, which snagged accelerated approval in February 2021 for two types of lymphoma based on small trials that didn’t assess whether patients lived longer. The company’s shares shot up 12% on the speedy approval.
But less than a year later, a larger study of TG Therapeutics’s drug in a third blood cancer found a potential increased risk of death when compared to patients on standard treatment.
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One of the problems is that sometimes drugmakers resist pulling a drug off the market, even after it’s obvious it doesn’t work. Makena, a drug to reduce the risk of premature birth, received a sped-up approval in 2011. Eight years later, a large trial found it didn’t work.
Yet it took another four years for the FDA to force it off the market. Makena, which was owned by a number of companies in its 12 years on the market, generated over $1.6 billion in sales.
The FDA is trying to take a stronger hand to get problematic drugs off the market. In February, it used a new “expedited withdrawal” procedure for the first time to rescind the approval for Pepaxto, a bone marrow cancer drug from Oncopeptides AB after the agency concluded that a new trial had failed to confirm the drug worked and actually suggested patients taking the drug died sooner.
Oncopeptides’ shares, which hit a two-year high in Swedish trading shortly after the accelerated approval in February 2021, have since lost more than 95% of their value.
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A company can also use more than one sped-up pathway on the same drug in the hopes of getting to market that much faster. In 2016, Eli Lilly & Co.’s cancer drug Lartruvo was approved after having snagged all four expedited pathways. The accelerated approval was based on one trial of 133 patients that showed promising survival results in sarcoma, a cancer that affects muscles and other soft tissues, even though the drug’s effect on slowing cancer growth weren’t clear cut.
Just over two years later, a larger study showed the drug had no effect on patient survival and Lilly pulled it from the market. …. In the short time Lilly’s drug was available, it sold more than $500 million.
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