Commentary
Video
Elevidys offers significantly higher dystrophin production than existing Duchenne muscular dystrophy treatments but requires intensive monitoring for adverse events.
In an interview with Pharmacy Times®, Craig McDonald, MD, chair of the department of physical medicine and rehabilitation at UC Davis Health, explains how delandistrogene moxeparvovec (Elevidys; Sarepta Therapeutics) marks a significant breakthrough in treatment for patients with Duchenne muscular dystrophy (DMD), a progressive and difficult-to-treat neuromuscular condition. According to McDonald, new clinical data suggest improved function and prolonged disease stability in DMD, positioning gene therapy as an emerging standard for patients aged 4 and older, though McDonald hopes of expanding to younger patients.
McDonald highlights the importance of pharmacists and patient care teams in monitoring for possible risks, including acute liver injury and myocarditis, and emphasizes that weekly patient follow-up in the months following treatment with Elevidys is essential.
Pharmacy Times: How does Elevidys compare with existing Duchenne muscular dystrophy (DMD) treatments in terms of efficacy and safety profiles?
1. Gene therapy is expected to become the primary treatment for DMD, with future expansion to younger patients potentially improving long-term benefits.
2. Patients need weekly follow-ups for at least 3 months to monitor for thrombocytopenia, myocarditis, and liver enzyme elevations (GGT levels).
3. Pharmacists are critical in counseling patients and caregivers about close monitoring, managing adverse effects with high-dose steroids, and ensuring adherence to safety protocols.
Craig McDonald, MD, UC Davis Health: I think Elevidys is really a transformational treatment for Duchenne patients. We've not seen this degree of improvement in a sustained fashion with any of the other treatments, such as corticosteroids. It produces a much higher level of replacement dystrophin on the order of, at times, 40% to 50% values of dystrophin, versus most Duchenne patients who have absence of dystrophin, whereas the exon skipping therapies that are available in Duchenne generally produce very low levels of dystrophin, a clinically important, measurable amount of dystrophin that can have an impact on disease progression. But the levels we see with exon skipping therapies are generally on the order of 3% to 5%, whereas the levels seen with Elevidys are on the order of 30% to 50%. I think, at least in my clinical experience now, following these patients for 4 years and beyond from the open label extension trials where we actually know they received Elevidys, I've been really quite impressed with their improvement in function. They have a higher peak obtained level of function, followed by longer-term disease stability. I think it's really been a transformational therapeutic compared to many of our other therapeutics used in DMD.
Pharmacy Times: What are the implications of these findings for the future management of DMD, particularly concerning gene therapy's role in treatment paradigms?
McDonald: Yeah, I think over time, gene therapy will become a standard of care treatment. I think it largely is emerging as a standard of care treatment for patients who are over the age of 4 with DMD; that's what the FDA-approved label allows us to treat, patients aged 4. I think long term, we hope to be able to treat patients younger, and we think we'll get even a greater long-term benefit if we can treat patients perhaps down to 2 years or even 6 months. Perhaps that will prompt us to actually begin to, on a national basis, do newborn screening for DMD. I think we do need more data, though, to determine if treatment of non-ambulatory patients who are older and more progressed in their disease can have a significant impact for those patients in terms of preserving their upper limb function, their breathing function, and their cardiac function.
Pharmacy Times: For pharmacists counseling patients and caregivers, what are the most critical considerations regarding the administration and monitoring of Elevidys?
McDonald: That's a really important point. This is not a benign therapy. There is potential for significant adverse events, which are all, for the most part, quite manageable, but we have to ensure that we're really going to be following patients very closely. Over the first 3 months after treatment, we generally see them in clinic on a weekly basis. We do laboratory monitoring for adverse events such as thrombocytopenia or [an] increase in troponin leak, which would be indicative of myocarditis or worsening cardiomyopathy. We also monitor them in terms of their liver enzymes, and namely the GGT level, which is what we use in Duchenne patients to monitor for acute liver injury. The acute liver injury is a common complication, which can occur in upwards of 30% of patients treated with gene therapy, and that requires treatment with high-dose peri-infusion steroids, prednisone dosages on the order of 2 mg/kg, or even use of solumedrol or methylprednisone alone, which are also used if the acute liver injury is becoming worse. These patients have to be very carefully monitored. I think all of these adverse events with Elevidys are monitorable and manageable, but it does require really close follow-up. The parents and the patients have to go into this knowing that they need to be followed very, very closely and be prepared to see the treating physicians in a very intense safety monitoring regimen, where they're seeing it at least once a week, if not more.
