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FDA Accepts Resubmission of BLA for Remestemcel-L in Pediatric Steroid-Refractory Acute Graft-Vs-Host Disease

The FDA has accepted the resubmission of a biologics license application (BLA) for remestemcel-L, aimed at treating pediatric patients with steroid-refractory acute graft-vs-host-disease (SR-aGVHD). This follows previous submissions and addresses chemistry, manufacturing, and control issues, with clinical data from the phase 3 MSB-GVHD001 trial supporting the application.

The FDA has accepted the resubmission of a biologics license application (BLA) for remestemcel-L (Ryoncil), targeting the treatment of pediatric patients with steroid-refractory acute graft-vs-host-disease (SR-aGVHD). The resubmission, made on July 8, 2024, addressed chemistry, manufacturing, and control issues. Mesoblast, the developer of remestemcel-L, was informed by the FDA in March 2024 that clinical data from the phase 3 MSB-GVHD001 trial were adequate to support another submission.

Silviu Itescu, MBBS, FRACP, chief executive officer of Mesoblast, expressed optimism about the potential approval of remestemcel-L for children with SR-aGVHD. The initial BLA for remestemcel-L received priority review from the FDA in April 2020, based on pooled data from three separate trials involving 309 pediatric patients with SR-aGVHD. Despite an 8 to 2 vote in favor of approval by the FDA’s Oncologic Drugs Advisory Committee in August 2020, a complete response letter (CRL) was issued in October 2020, requesting additional data.

The MSB-GVHD001 trial enrolled 54 pediatric patients with aGVHD who did not respond to steroids, showing an overall response rate (ORR) of 70.4% at day 28, significantly higher than the prespecified ORR of 45%. The 100-day overall survival (OS) rate was 87% for patients who achieved a response at day 28, compared to 47% for those who did not. Additionally, the 28-day ORR was 70% for remestemcel-L compared with 43% in a matched control group, with respective 100-day OS rates of 74% vs 57%.

A propensity-matched study showed that 67% of high-risk pediatric patients treated with remestemcel-L experienced a response at day 28 and were alive after 180 days, compared to 10% for the control group. A 4-year survival study included 51 evaluable patients with SR-aGVHD treated during the phase 3 trial, showing 6-month, 1-year, 2-year, and 4-year OS rates of 67%, 63%, 51%, and 49%, respectively.

MSB-GVHD001 was a single-arm, prospective trial enrolling pediatric patients between 2 months and 17 years of age with grade B to D aGVHD requiring systemic therapy with corticosteroids. Patients received remestemcel-L at 2 x 106 MSCs/kg twice per week for 4 consecutive weeks, with the option for additional treatment in the event of an aGVHD flare up. The trial's primary end point was ORR at day 28, with 100-day OS rate as a secondary end point.


Reference News

FDA Accepts Resubmission of BLA for Remestemcel-L in ...

FDA accepted Mesoblast's resubmitted BLA for remestemcel-L (Ryoncil) to treat pediatric SR-aGVHD, addressing prior issues. Phase 3 trial data showed a 70.4% ORR at day 28 and 87% 100-day OS for responders, supporting its potential approval.

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