National agency pushback against EMA fast track continues

Germany’s healthcare cost watchdog is continuing to push back against the European Medicines Agency’s (EMA) plans to accelerate the approval of new medicines. The German institute worries fast-track drug approvals based on limited clinical trial data or real-world evidence will become the norm—and that this will undermine attempts to gauge the true safety and efficacy of medicines.

EMA has spent the past few years developing and piloting a scheme that would allow companies to win approval in a restricted patient population on the basis of limited data, before going on to generate additional clinical real-world evidence to support wider use of the drug. The regulator rejected most applications to join the pilot scheme—bluebird bio and Immunocore were among the successful companies—but Germany's Institute for Quality and Efficiency in Health Care (IQWiG) nonetheless fears its ideas will creep into standard practice.

“Accelerated approval on the basis of reduced data should be limited to special situations. But there is reasonable concern that it is intended to become the norm,” Stefan Lange, deputy director of IQWiG, told Reuters.

Officials at IQWiG first fired off a volley against EMA’s adaptive pathways program in August, weeks after the European Union-wide regulatory agency published its final report on a pilot project of the scheme. At that time, IQWiG said “neither industry nor EMA has a concept as to how real-world data can be used after drug approval to allow drawing reliable conclusions on benefit and harm.” Given the importance to the scheme of drawing conclusions from real-world data, IQWiG said it may be “high time to pause for a moment and rethink the whole concept.”

EMA hit back at IQWiG through the press, telling Pharmalot it rejected the conclusions of the German institute. As EMA sees it, the current shortcomings in plans to use real-world data are testament to the need to continue working with drug developers, not cause to scrap the scheme altogether.

Lange’s latest comments suggest IQWiG remains sceptical about whether these shortcomings can be resolved. To approve drugs on the basis of studies that lack control arms, EMA may use historic patient data to assess how the experimental therapy performs against standard of care. Lange has big doubts about the validity of such comparisons.

“Any attempt to statistically eliminate the distortions from these selection mechanisms afterwards is bound to fail,” he said.

The concern is compounded by the likely effect of provisional approvals on enrollment in clinical trials. Once some patients can access the medicine, investigators may struggle to persuade others to enter into randomized trials in which they may receive standard of care or placebo, not the new drug.

IQWiG has been the most vocal about its concerns—and as a big player in Europe’s largest drug market has significant clout—but it isn’t the only national agency to question the scheme. Officials in France also have “mixed feelings.” And Reuters reports smaller countries have privately expressed reservations.

The United Kingdom’s National Institute for Health and Care Excellence (NICE) is a high-profile advocate of the adaptive pathways pilot program. But with the U.K. heading toward the EU exit, its influence over region-wide policy could wane over the next few years.

This situation is a microcosm of broader concerns about the effect of Brexit. Generally, the U.K. argues for a faster, lighter-touch approach to regulation than some of its neighbors on mainland Europe. If the Medicines and Healthcare Products Regulatory Agency (MHRA) ceases to have any influence over EMA, some people fear the EU-wide regulator’s appetite for fast approvals may wane.

As drug development consultancy NDA discussed this week, EMA is yet to embrace expedited approvals to the extent FDA has. Last year, the EU approved seven drugs using procedures such as conditional and accelerated pathways. The regulator is pushing on multiple fronts to move faster, but speedy approvals remain the exception rather than the norm.