Risks of accelerated approval

USA authorizes cancer treatments eight months before Europe, but study suggests this lead should be viewed with skepticism

Ricardo Muniz

A study by scientists from the USA, Canada, and the UK revealed that of 89 new oncology therapies approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) between 2010 and 2019, 95% were approved by the American agency first, with EU market authorization granted an average of 241 days later.

The results were published in the journal JAMA Network Open. According to the study’s lead author, pharmacologist Mark Lythgoe of Imperial College London, the European “delay” remains relatively unchanged from a decade ago. But an eight-month gap is highly significant, exceeding the life expectancy of many people with advanced cancer, the British expert stresses.

“The FDA’s accelerated approval process has provided access to many innovative drugs that have positively transformed the lives of thousands of patients,” Lythgoe told ScienceArena. As an example, he highlights the antitumor medication imatinib—currently sold under the brand name Gleevec by multinational pharmaceutical company Novartis—which has revolutionized the treatment of chronic myeloid leukemia, a rare type of cancer that affects blood cells.

“Faster approval, however, is a double-edged sword,” says the scientist. The FDA has had to subsequently withdraw more newly approved cancer drugs from the market than the EMA. This may suggest that shorter evaluation processes do not always translate into better results.

Lythgoe mentions another JAMA study, published in 2019, which showed that of 93 cancer drugs granted accelerated approval by the FDA, only 19 (20%) led to improved survival. “Approval speed and volume should only be celebrated if they deliver more significant results, giving the patient a better and longer life,” says Lythgoe.

Ali Raza Khaki, an oncologist at Stanford University School of Medicine, California, and coauthor of the paper, emphasizes that the group’s findings cannot be directly related to the amount of bureaucracy involved at the regulatory agencies or the level of caution with which decisions are made.

Of 93 cancer treatments granted accelerated approval by the FDA, only 19 improved survival rates.

Both researchers, however, draw attention to the fact that the EMA’s authorization process involves two separate stages. The first is approval by the Committee for Medicinal Products for Human Use, followed by mandatory centralized approval by the European Commission. The second stage alone increases the length of the process by an average of 62 days. In contrast, the FDA offers “expedited” approval pathways, including the so-called “breakthrough therapy designation,” which recognizes drugs that offer substantial improvements over available therapies.

But while the EMA withdrew fewer treatments from the market, it also approved fewer than the FDA prior to the publication of pivotal trial results. “These results are important because they give the medical community data on who is most likely to benefit, as well as complete and clear information about the risks and advantages of the therapy and how to manage toxicity,” Khaki explained to ScienceArena.

Questions over the benefits

The limitations of accelerated drug approval were also highlighted by Kristina Jenei, a researcher from the School of Population and Public Health at the University of British Columbia in Vancouver, Canada. In a commentary published in JAMA, Jenei argued that shorter approval times create greater uncertainty about a treatment’s real benefits, exposing patients to additional risks, such as drug toxicity.

This is exacerbated, says Jenei, by inefficiencies in follow-up studies and postmarketing confirmation of clinical benefits. The scientist also warns of what she says is an underappreciated challenge imposed by FDA procedures. “The increased speed of approval in the USA combined with inconsistent follow-up of postmarketing studies lowers global testing standards,” she wrote.

Finally, Jenei points out that the USA is the largest pharmaceutical market in the world and is therefore prioritized by manufacturers as part of their pricing strategy. In fact, 72% of companies submitted drug-approval applications to the FDA before submitting them to the EMA.

“This approach might demonstrate a corporate tactic to launch drugs in countries willing to pay higher prices, which in turn increases prices globally. Other countries must then negotiate with drug prices that were designed for the US market,” said Jenei.

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