RARE Daily

What, Me Worry? Another Down Year for Novel, Rare Disease Drug Approvals

January 17, 2023

The effects of the COVID-19 pandemic, the war in Ukraine, and the subsequent economic downturn have caused drug developers to trim their pipelines and focus on programs with near-term and best chances for success. Perhaps the best indicator of the long-term impact these developments will have on bringing new therapies to rare disease patients, albeit a lagging one, will be the number of novel therapies approved by the U.S. Food and Drug Administration.

It may be years, if ever, that such manifestations may be seen. It’s unclear whether any of these factors weighed on drug approvals in 2022, but it was a down year for FDA approvals of novel therapies, the second year in a row that the number of novel orphan drugs approved by the agency declined from the previous year.

The FDA’s Center for Drug Evaluation and Research approved 20 novel therapies for rare disease in 2022, 54 percent of all novel drugs the division approved in 2022. That represented a 23 percent decline in the number of novel orphan drugs approved compared to the 26 the agency approved the previous year. A total of nine of novel orphan drug approvals, 45 percent, were for medicines to treat rare cancers. The approvals are often used as a proxy for innovation and as a measure of industry R&D productivity. Some may worry that we have an innovation problem.

Of the 20 novel, rare disease drug approvals in 2022, 12 were first-in-class therapies, 9 had Breakthrough Therapy designation, and the agency granted 14 of them Priority Review. Six of the therapies were approved under the accelerated approval pathway.

Amylyx Pharmaceuticals’ Relyvrio was among the noteworthy drugs approved in 2022. Relyvrio is an oral combination therapy for the rare, neurodegenerative disease amyotrophic lateral sclerosis, a progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death.

Other noteworthy approvals came from the FDA’s Center for Biologics Evaluation and Research, which approved three novel gene therapies in 2022. This included Bluebird Bio’s Skysona for cerebral adrenoleukodystrophy and the company’s Zynteglo for beta thalassemia, as well as CSL Behring’s Hemgenix for hemophilia B.

People who are worried that two down years of approvals represents a cause for concern can channel their inner Alfred E. Newman and take solace in the journalism adage: “Three is a trend.” To worry now would be premature. Worry next year.

On the other hand, worrying that only 20 novel orphan drugs won approval rather than 26 is a bit like worrying about having an umbrella in a storm when dams have burst open. There’s a much bigger problem than keeping your head dry that needs to be addressed.

The sad truth is we are discovering diseases at a far faster rate then we are treating them. While the patients who benefit from these new drugs may welcome them, applying the model from drug development and regulatory review is ill suited to address the need of patients suffering from nearly 11,000 rare diseases, the vast majority of which are without an approved therapy and have too small a patient population to expect conventional drug development efforts to benefit patients with those conditions.

We do have an innovation problem, but it’s not with regards to science. We need new approaches that transcend the way we develop, test, review, and make drugs for ultra-rare diseases. Picking off conditions one at a time and relying on large-scale manufacturing to make them cost effective, isn’t going to hack it.

Editors note: This chart was updated 1/27/23 to correct a misstated designation.

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