Hot topic: FDA’s ‘plausible mechanism’ pathway could boost cell and gene therapies
Good news for developers of drugs for ultra-rare diseases – including cell and gene therapy firms – in the form of a new way of assessing them that’s being proposed by the US’s Food and Drug Administration (FDA).
The regulator is looking at introducing what it calls a “plausible mechanism” pathway. This would allow approval of medicines for ultra-rare diseases, if there are very good reasons to believe they would work.
The problem of getting approvals of drugs for ultra-rare diseases has become more acute as our understanding of them, and our ability to treat them, has improved.
Scientists can now pinpoint the exact gene mutations that cause ultra-rare diseases. In many cases, a specific genetic fault might only be shared by a few dozen people worldwide. Carrying out randomised controlled trials in diseases with such tiny patient population is clearly impossible.
Major regulators such as the FDA and the EU’s European Medicines Agency (EMA) have long recognised this problem, and have a variety of existing mechanisms in place to ensure therapies for rare and ultra-rare disease can be approved.
Nonetheless, drug developers and patient groups have consistently argued that securing approval can still be a real headache.
With that in mind, FDA Commissioner Martin Makary and Center for Biologics Evaluation and Research Director Vinay Prasad recently wrote a short article in the New England Journal of Medicine outlining how this new plausible mechanism pathway might work.
The “PM pathway”, they said, would be limited to conditions known to be caused by a clear molecular or cellular abnormality – and would not be allowed for medicines intended to tackle conditions defined by a range of diagnostic criteria or genome-wide associations.
The proposed medicine would have to directly target the abnormality, and there would have to be strong prior evidence that it did so (e.g. from animal models).
In addition, of course, there would have to be strong evidence of clinical improvement when the medicine was finally tested in humans.
Once a drug maker had shown success treating several patients, the FDA would then “move towards” granting marketing authorisation.
What’s important to note is that authorisation could be granted not just for a single medicine – which might be a bespoke treatment for just a single individual – but for a suite of similar medicines based on the same platform. This is something experts such as CRISPR authority Fyodor Urnov have long called for.
Lots of details have to be ironed out. Law firm Ropes and Gray, for instance, argued that “significant open questions … remain regarding its implementation”.
Nonetheless, the PM pathway is being welcomed as a small but significant step forward, that should help aid the approval of highly personalised medicines.
In a recent note, Singer Capital Markets commented: “The proposed pathway has the potential to be one of the most transformational and sensible changes to come out of the new look HHS (Health & Human Services).
“It rationally enables bespoke gene therapies to follow a more realistic approval framework, without comprising on review standards. In our view, a positive tailwind for cell & gene therapies.”
