After I was first identified with limb girdle muscular dystrophy (LGMD), I used to be devastated to study there wasn’t any remedy or remedy. For these of us dwelling with progressive ailments, time is just not impartial. Each month a promising remedy is delayed, we can have irreversible lack of muscle operate.
Uncommon illness drug improvement is within the midst of a rare period of scientific innovation. Researchers are advancing gene therapies and focused remedies unimaginable only a decade in the past. The Meals and Drug Administration has alternatives right now with new management to modernize, together with the utilization of revolutionary trial designs and instruments so the USA continues to guide the world in uncommon illness drug improvement.
Particularly, with the Meals and Drug Omnibus Reform Act (FDORA) of 2022, Congress enabled the FDA to make the most of a software known as platform expertise designation to modernize drug improvement. The concept was wise and even elegant: When an organization makes use of the identical underlying expertise or platform — say, the identical viral vector to ship a gene — throughout a number of ailments, it mustn’t have to start out over each time. What’s realized in a single program for one illness ought to carry ahead to the following. Platforms are imagined to be about effectivity. They’re supposed to maneuver improvement ahead.
However sufferers, clinicians, advocacy organizations, biotechnology leaders, and members of Congress have raised rising considerations that FDA’s latest actions are creating better uncertainty and that the company is failing to constantly apply the regulatory flexibility Congress supposed for uncommon ailments. Too usually, FDA is misapplying the very instruments Congress created to speed up remedies. One instance is how FDA is implementing platform expertise designation. In reality, it has turned the logic inside out. LGMD sufferers like me are paying the worth.
In June 2025, the FDA awarded Sarepta a platform expertise designation for the viral vector behind its muscular dystrophy gene therapies, together with a remedy for a subtype of LGMD referred to as LGMD2E/R4. It was a landmark second.
However over a month later, the FDA revoked the platform designation and positioned a maintain throughout all the corporate’s trials after the tragic deaths of three nonambulatory people constructed on that shared vector: two Duchenne sufferers and one LGMD 2D/R3 affected person. These deaths halted every little thing, and for good motive. Researchers wanted to reassess the chance and uncover if there’s a totally different security profile for the nonambulatory inhabitants. This was a horrible time for each the DMD and LGMD communities. As a affected person neighborhood, all of us nonetheless consider these folks and their households every day.
STAT Plus: Affected person dies in Sarepta gene remedy trial, including to security considerations
Not too lengthy after, the LGMD2E/R4 Part 3 trial was nearing completion for a separate subtype. The corporate was getting ready to file for approval inside the subsequent few weeks, but the complete program for this subtype was additionally positioned on maintain for ambulatory and nonambulatory. Sufferers and households had been left asking why ambulatory LGMD sufferers couldn’t proceed towards assessment whereas the dangers in nonambulatory sufferers had been studied individually. Then FDA made one other determination that left LGMD households much more confused.
FDA has since allowed entry/dosing to renew for the associated Duchenne remedy, constructed on the exact same platform, for sufferers who can nonetheless stroll.
So, the company used the platform to justify stopping every little thing, however the cautious, patient-by-patient benefit-risk judgment that restored entry was utilized to just one illness state. The LGMD 2E/R4 sufferers stay on medical maintain, and the potential remedy can not transfer ahead for approval even for ambulatory sufferers at the moment.
This isn’t a one-off prevalence. In January, FDA positioned a medical maintain on a gene remedy for one type of the uncommon illness Hurler syndrome, a extreme type of mucopolysaccharidoses referred to as MPS, after a tumor was present in a younger affected person who obtained the gene remedy. FDA then prolonged the maintain to a separate remedy for a really critical however totally different illness, Hunter syndrome, citing shared threat. Nevertheless, not one of the 32 Hunter syndrome sufferers handled in that second program, some dosed practically seven years earlier, had proven related outcomes.
These very critical ailments, which regularly have pediatric onset, are sometimes deadly and progressively debilitating, so households are determined for a remedy. Discover the sample: When the query is threat, FDA extrapolates freely throughout merchandise and throughout ailments. When the query is gathered data with years of security and efficacy information, refined dosing, and higher affected person choice, sponsors are informed that data doesn’t go the opposite means.
Up to now month, the brand new FDA management has lifted the maintain on Hunter syndrome and reconsidered this system’s approval pathway. That reversal was welcome, nevertheless it underscores the necessity for a constant framework governing when threat is transferred throughout applications in platforms. This situation has main ramifications throughout uncommon illness drug improvement, as sponsors want predictability to make the most of revolutionary instruments comparable to platform designation and even basket trials.
I need to be clear: I’m not saying hostile occasions don’t matter. They matter enormously, they usually deserve critical, pressing investigation. However the platform designation was designed to extend effectivity and pace the trail of remedies. But, it appears to be doing simply the other. A promising remedy for LGMD2E/R4 continues to be on maintain, and whereas ambulatory sufferers are ready, their muscular tissues are deteriorating. This subtype of LGMD is ultra-rare so one other drug developer is unlikely to step up.
Regulators should be cautious to not block a whole illness neighborhood from a probably life-changing remedy whereas all of us work to grasp a threat that could be totally different and better in a sure subgroup. Whereas ready, these sufferers progress and lose operate. Moreover, as the sector of adeno-associated virus (AAV) gene remedy grows in data, this can be very vital to grasp how we are able to extra safely shield sufferers with enhanced immunosuppression regimes now and never later. What number of fatalities have to happen in AAV gene remedy when rising consensus is pointing to sirolimus to forestall liver hepatotoxicity?
That is an pressing situation for the uncommon illness neighborhood that deserves the eye of Congress. It created the platform expertise designation to make improvement extra environment friendly, to not create a one-way system during which threat travels rapidly however all data, together with constructive data, travels slowly. The FDA should shield sufferers from treatment-related hurt, nevertheless it should additionally account for the irreversible hurt attributable to doing nothing. For folks dwelling with progressive uncommon ailments, each dangers are actual.
As Congress considers FDA reforms to accompany reauthorization of the Prescription Drug Person Charge Act, I urge them to ship a transparent message to FDA that Congress expects FDA to make the most of the provisions within the twenty first Century Cures Act like novel trial design for uncommon ailments whereas additionally advancing the efficient software of platform applied sciences from FDORA.
With new FDA management, uncommon illness remedies have to take precedence. Sufferers like me and others can’t wait.
Kat Bryant Knudson is the founder and CEO of The Converse Basis, a patient-led nonprofit advancing care, analysis, advocacy, and remedy improvement for folks dwelling with limb girdle muscular dystrophy. Disclosure: Sarepta offered restricted grants to the Converse Basis in 2024 and 2025 to help affected person applications.
