Opinion: Limb girdle muscular dystrophy patients face a maddening reality

When I was first diagnosed with limb girdle muscular dystrophy (LGMD), I was devastated to learn there wasn’t any treatment or cure. For those of us living with progressive diseases, time is not neutral. Every month a promising therapy is delayed, we will have irreversible loss of muscle function. Rare disease drug development is in the midst of an extraordinary era of scientific innovation. Researchers are advancing gene therapies and targeted treatments unimaginable just a decade ago. The Food and Drug Administration has opportunities today with new leadership to modernize, including the utilization of innovative trial designs and tools so the United States continues to lead the world in rare disease drug development. In particular, with the Food and Drug Omnibus Reform Act (FDORA) of 2022, Congress enabled the FDA to utilize a tool called platform technology designation to modernize drug development. The idea was sensible and even elegant: When a company uses the same underlying technology or platform — say, the same viral vector to deliver a gene — across multiple diseases, it should not have to start over every time. What is learned in one program for one disease should carry forward to the next. Platforms are supposed to be about efficiency. They are supposed to move development forward. But patients, clinicians, advocacy organizations, biotechnology leaders, and members of Congress have raised growing concerns that FDA’s recent actions are creating greater uncertainty and that the agency is failing to consistently apply the regulatory flexibility Congress intended for rare diseases. Too often, FDA is misapplying the very tools Congress created to accelerate treatments. One example is how FDA is implementing platform technology designation. In fact, it has turned the logic inside out. LGMD patients like me are paying the price. In June 2025, the FDA awarded Sarepta a platform technology designation for the viral vector behind its muscular dystrophy gene therapies, including a therapy for a subtype of LGMD known as LGMD2E/R4. It was a landmark moment. But over a month later, the FDA revoked the platform designation and placed a hold across all the company’s trials after the tragic deaths of three nonambulatory individuals built on that shared vector: two Duchenne patients and one LGMD 2D/R3 patient. These deaths halted everything, and for good reason. Researchers needed to reassess the risk and discover if there is a different safety profile for the nonambulatory population. This was a terrible time for both the DMD and LGMD communities. As a patient community, we all still think of these people and their families daily. Not too long after, the LGMD2E/R4 Phase 3 trial was nearing completion for a separate subtype. The company was preparing to file for approval within the next few weeks, yet the entire program for this subtype was also placed on hold for ambulatory and nonambulatory. Patients and families were left asking why ambulatory LGMD patients could not continue toward review while the risks in nonambulatory patients were studied separately. Then FDA made another decision that left LGMD families even more confused. FDA has since allowed access/dosing to resume for the related Duchenne therapy, built on the very same platform, for patients who can still walk. So, the agency used the platform to justify stopping everything, but the careful, patient-by-patient benefit-risk judgment that restored access was applied to only one disease state. The LGMD 2E/R4 patients remain on clinical hold, and the potential treatment cannot move forward for approval even for ambulatory patients at this time. This is not a one-off occurrence. In January, FDA placed a clinical hold on a gene therapy for one form of the rare disease Hurler syndrome, a severe form of mucopolysaccharidoses known as MPS, after a tumor was found in a young patient who received the gene therapy. FDA then extended the hold to a separate therapy for a very serious but different disease, Hunter syndrome, citing shared risk. However, none of the 32 Hunter syndrome patients treated in that second program, some dosed nearly seven years earlier, had shown similar outcomes. These very serious diseases, which often have pediatric onset, are often fatal and progressively debilitating, so families are desperate for a treatment. Notice the pattern: When the question is risk, FDA extrapolates freely across products and across diseases. When the question is accumulated knowledge with years of safety and efficacy data, refined dosing, and better patient selection, sponsors are told that information doesn’t go the other way. In the past month, the new FDA leadership has lifted the hold on Hunter syndrome and reconsidered the program’s approval pathway. That reversal was welcome, but it underscores the need for a consistent framework governing when risk is transferred across programs in platforms. This issue has major ramifications across rare disease drug development, as sponsors need predictability to utilize innovative tools such as platform designation or even basket trials. I want to be clear: I am not saying adverse events don’t matter. They matter enormously, and they deserve serious, urgent investigation. But the platform designation was designed to increase efficiency and speed the path of treatments. Yet, it seems to be doing just the opposite. A promising treatment for LGMD2E/R4 is still on hold, and while ambulatory patients are waiting, their muscles are deteriorating. This subtype of LGMD is ultra-rare so another drug developer is unlikely to step up. Regulators must be careful not to block an entire disease community from a potentially life-changing therapy while we all work to understand a risk that may be different and higher in a certain subgroup. While waiting, these patients progress and lose function. Additionally, as the field of adeno-associated virus (AAV) gene therapy grows in knowledge, it is extremely important to understand how we can more safely protect patients with enhanced immunosuppression regimes now and not later. How many fatalities need to occur in AAV gene therapy when growing consensus is pointing to sirolimus to prevent liver hepatotoxicity? This is an urgent issue for the rare disease community that deserves the attention of Congress. It created the platform technology designation to make development more efficient, not to create a one-way system in which risk travels quickly but all knowledge, including positive information, travels slowly. The FDA must protect patients from treatment-related harm, but it must also account for the irreversible harm caused by doing nothing. For people living with progressive rare diseases, both risks are real. As Congress considers FDA reforms to accompany reauthorization of the Prescription Drug User Fee Act, I urge them to send a clear message to FDA that Congress expects FDA to utilize the provisions in the 21st Century Cures Act like novel trial design for rare diseases while also advancing the effective application of platform technologies from FDORA. With new FDA leadership, rare disease treatments need to take priority. Patients like me and others can’t wait. Kat Bryant Knudson is the founder and CEO of The Speak Foundation, a patient-led nonprofit advancing care, research, advocacy, and treatment development for people living with limb girdle muscular dystrophy. Disclosure: Sarepta provided limited grants to the Speak Foundation in 2024 and 2025 to support patient programs.