As indicated below, this decision is not final. Mesoblast are in the process of lodging a dispute resolution request, which the FDA are legally required to assess in good faith. As I discuss below, there is still a likelihood Ryoncil will still be approved since we have the advantage of going through the accelerated approval pathway.
In the type A meeting, Mesoblast will argue: 1. There are currently no approved treatments for SR aGvHD in pediatric patients 12 and under and this is an unmet condition that has a high mortality rate. 2. The treatment has proven efficacy. 3. The precedent for approval using a single-arm trial has already been set by the FDA approving Ruxolitinib in 2019. 4. A post-marketing study in Adults to satisfy the concerns of the FDA.
The fundamental question is whether the FDA will meet Mesoblast halfway by overturning the CRL and issuing an approval letter, whilst allowing Mesoblast to perform a post-marketing study in Adult SR aGvHD patients. This will be the most ideal pathway for both the FDA and Mesoblast. Can the FDA and Mesoblast reach a compromise? Or will the FDA be unrelenting and request an additional clinical trial before approval is granted.
Let's look at a case study for Sarepta where a CRL was overturned in December last year. This is the pathway Mesoblast will be pursuing. Will the FDA show the same courtesy to Mesoblast?
In stunning reversal, FDA clears Sarepta DMD drug it rejected 4 months ago
"Out of nowhere, the agency Thursday granted accelerated approval to Sarepta’s Vyondys 53 (golodirsen), a drug it turned down in August for safety reasons. The go-ahead covers about 8% Duchenne patients whose dystrophin gene bears a certain mutation amenable to exon 53 skipping."
"While the FDA didn’t elaborate on the sudden change of course, Sarepta said it had launched a formal dispute resolution request after receiving the agency's complete response letter (CRL) detailing its reasons for the rejection. Sarepta worked with Peter Stein, director of the FDA's Office of New Drugs, to resolve the concerns raised in that CRL."
The win confirmed “that dystrophin is an adequate surrogate for accelerated approval, and FDA’s continuing flexibility in areas of high unmet need like DMD,” RBC Capital Markets analyst Brian Abrahams wrote in a Thursday note to clients. It also showed that Sarepta “still has a productive and collaborative relationship with the agency, which should help them navigate the paths for the gene therapies,” he added
For Vyondys 53, its approval is again conditional upon Sarepta running a confirmatory trial. The company is already conducting one, called Essence, which is designed to assess whether the drug improves motor function in its indicated patient population. Data aren't expected for almost five years, however.
“If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug,” the agency said Thursday. Nevertheless, RBC’s Abrahams said his team reviewed “it unlikely that the results of Essence fail to show functional benefits to the level that would support continued marketing of Vyondys” after it reads out around 2024.
“The FDA recognizes the urgent need for new medical treatments for serious neurological disordersand we have a long-standing commitment to working with researchers, drug companies and patients to facilitate the development and approval of treatments for rare diseases...... “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
“Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness.
Vyondys 53 was approved under the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments.
This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit.
In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease and the lack of available therapy.
Vyondys 53 was evaluated in a two-part clinical study. The first part included 12 DMD patients, with eight patients receiving Vyondys 53 and four receiving placebo. The second part of the study was open-label, and included the 12 patients enrolled in part one of the study, and 13 additional patients who had not previously received the treatment.
As part of the accelerated approval process, the FDA is requiring the company to conduct a clinical trial to confirm the drug’s clinical benefit. The ongoing study is designed to assess whether Vyondys 53 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.
The FDA granted this application Fast Track and Priority Review designations. Vyondys 53 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. In addition, the manufacturer received a rare pediatric disease priority review voucher. The FDA’s rare pediatric disease priority review voucher program is intended to encourage development of new drugs and biologics to prevent and treat rare diseases in children.
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