Study: One-fifth of recent FDA approved drugs not authorized, reimbursed in other countries

More than one-fifth of drugs recently approved by the US Food and Drug Administration (FDA) were not approved or recommended for public reimbursement in other countries, according to a recent study published in JAMA Internal Medicine.

“This cross-sectional study demonstrated that more than one-fifth of the new drugs approved by the FDA in 2017 through 2020 were either refused marketing authorization or not recommended for reimbursement in Australia, Canada, or the UK as of May 2022 due to unfavorable benefit-to-risk profiles, uncertain clinical benefit, or unacceptably high price,” Catherine Pham, PharmD, MPH, of the Pharmacy Outcomes Research Group at Kaiser Permanente National Pharmacy in Downey, CA, and colleagues wrote in their study.

“Most of the drugs refused marketing authorization or not recommended for public reimbursement internationally were initially approved by the FDA under the Orphan Drug Act or at least 1 expedited regulatory pathway,” they said.

Pham and colleagues analyzed regulatory decisions and health technology assessments (HTAs) made by regulators and agencies in Australia, Canada and the UK regarding drugs approved by the FDA between 2017 and 2020. The researchers also examined the cost of each drug for a patient in the US for drugs that HTAs issued a negative recommendation.

In total, 206 new drugs were approved by the FDA in this timeframe, and 162 drugs (78.6%) received marketing authorization by one or more other countries at a median of 12.1 months following FDA approval. The European Medicines Agency (EMA) refused marketing authorization for 5 drugs approved by the FDA after an unfavorable benefit-to-risk assessment: abaloparatide for osteoporosis, betrixaban for venous thromboembolism prophylaxis, emapalumab for primary hemophagocytic lymphohistiocytosis, istradefylline for Parkinson disease and pexidartinib for symptomatic tenosynovial giant cell tumor. In four cases, the EMA cited inadequate study results as the reason for refusal, while the fifth case (pexidartinib) was due to the drug showing a small improvement in symptoms. Abaloparatide was also refused marketing authorization based on cardiac safety concerns, while betrixaban carried concerns of bleeding and pexidartinib had hepatic safety concerns.

Researchers also found 42 drugs approved by the FDA had at least one HTA agency in Australia, Canada or the UK issue a negative reimbursement recommendation because of uncertain clinical benefits or high prices. When Pham and colleagues analyzed the cost of each drug for 42 drugs that had a negative recommendation for reimbursement, they found the annual median cost per patient was $123,432; of these, 25 drugs had an estimated cost higher than $100,000. Ozenoxacin was the least expensive drug at $312 for a 5-day treatment course, while cerliponase alfa was the most expensive at $755,898.

Overall, 20 drugs had oncology indications, and 36 drugs were approved with orphan drug designation or under the priority review, accelerated approval, breakthrough therapy or fast track programs, the researchers said.

“It has been argued that drugs for which there is unclear clinical benefit, such as those granted expedited marketing authorization in the US based on surrogate end points, should be discounted in cost accordingly with the level of uncertainty,” Pham and colleagues said. “Future analyses should evaluate US utilization, pricing disparities, and clinical outcomes of FDA-approved drugs with limited international market presence. Further research is needed to elucidate the differences in perceived value of specific drugs among various countries, including the US.”

JAMA Intern Med Pham et al.

Study: One-fifth of recent FDA approved drugs not authorized, reimbursed in other countries

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