Why the FDA’s ‘fast track’ approval process is bad for cancer therapy around the world

When it comes to cancer drugs, the US Food and Drug Administration is willing to go where other regulators are not.

A new study found that the FDA has granted accelerated review and approval to dozens of cancer drugs that were either not reviewed or denied authorisation by the European Medicines Agency (EMA) or the UK’s NICE, usually due to a lack of strong efficacy data or cost-effectiveness.

“The accelerated approval process was developed to facilitate the approval of drugs that address unmet medical needs by allowing regulatory approval based on unvalidated surrogate measures,” wrote study authors led by Avi Cherla, of the London School of Economics and Political Science, in JAMA Internal Medicine. Those surrogate endpoints, such as tumour response or progression-free survival (PFS), are not as often used in EMA and NICE approvals.

Between 1992 and 2017, the FDA used the accelerated process to approve 93 cancer drug indications; six of those were withdrawn, leaving 87 such indications on the market.

A total of 73 of those indications were reviewed by the EMA, and five were denied authorisation. Of the 68 indications granted by the EMA, 11 were not reviewed by NICE and five are currently undergoing review. In total, 45 of the drug indications were recommended by NICE for NHS coverage.

The reasons given by NICE and EMA for either not reviewing or not recommending the drugs in question tended to focus on a lack of efficacy data and poor cost-effectiveness. For example, carfilzomib was authorised by the FDA and EMA for treatment of multiple myeloma based on response rate and PFS, but NICE did not recommend its authorisation because overall survival data were immature and the cost per quality-adjusted life-year (QALY) was “likely to be substantially >£41,429.”

In the US, cost-effectiveness is not routinely considered in approvals, and Medicare has no ability to negotiate prices with drug companies. Most of the drugs from this study that NICE did approve were contingent on the negotiation of additional confidential discounts or imposition of restricted indications.

It may seem as though other countries are simply being more cautious in their approach to cancer drug approvals and the FDA’s looser efforts would be confined to the US market, but there is likely an external effect of those accelerated approvals.

“The US approach provides little downward market pressure and works to keep drug prices high,” wrote Dr Vinay Prasad and Dr Myung Kim, of the University of California, San Francisco and the Oregon Health and Science University, respectively, in an accompanying editorial. “High prices make the US the most valuable market for new drugs, which in turn leads to global development of drugs with marginal or unproven benefit and little focus on cost-effectiveness.”

The attempt to bring cancer drugs to market faster in the US, though well-intentioned, has led to development and approval of many expensive drugs with substantial uncertainty regarding their actual benefit. As a result, other high-income nations either delay or deny those medications, due to the lack of solid efficacy and value data.

“The lack of information regarding clinical end points, a consequence of the low US regulatory bar, makes it more difficult for other countries to obtain the evidence they need to justify coverage,” Drs Prasad and Kim wrote. “It is hard to not view the entire global cancer drug ecosystem as broken.”

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