Ann: FDA Advisory Committee Sets Review Date for Remestemcel-L, page-461

FDA breifing notes whats good. my biased view.

On 1/31/2020, the Applicant submitted BLA 125706 for remestemcel-L for treatment of SRaGVHD in pediatric patients with the results of Protocol MSB-GVHD001 as the sole basis of efficacy. To obtain marketing approval, the Food Drug and Cosmetics Act (FD&C Act) requires that sponsors provide substantial evidence of safety and efficacy of their products based on the conduct of adequate andwell-controlled studies.

It is of interest that the Day-28 ORR is consistently 64% - 69% in remestemcel-L-treated pediatric patients with or without additional standard care salvage therapy (Table 7).

Further, the pediatric subpopulation comparison within Protocol 280 appears to have a substantial numerical difference between treatment arms for Day-28 ORR, but as this is analysis of a small subgroup (note broad confidence intervals), the results might be appropriate for only hypothesis generation, but would not generally be considered evidence of a treatment effect.

Protocol MSB-GVHD001 met its primary objective; the Day-28 ORR was 69.1% (95% CI: 55.2,80.9) in the FAS. The primary endpoint results in MSB-GVHD001were statistically significant, the measured response was durable (median 54 days), and the results were consistent across sub populations and secondary efficacy endpoints.

Due to these design differences, it is unclear that these study results are relevant to the proposed indication for use of remestemcel-L as a single-agent treatment of SR-aGVHD in pediatric patients, but it raises the uncertainties associated with interpreting the observed efficacy outcomes between studies.

The safety population (n = 54) included all subjects who received at least 1 dose of remestemcelL. FDA safety analysis confirmed the Applicant’s safety analyses (see Applicant's Briefing Document Section 6.2.2) and revealed no safety signal of concern In general, no safety signal of concern was identified in the studies of remestemcel-L.

The Applicant is seeking approval of remestemcel-L for the indication of treatment of steroid-refractory acute graft-versus-host disease in pediatric patients based on results from a single trial, Protocol MSB-GVHD001.

Although the study reached the primary endpoint goal of a 28-day ORR at 69.1%, it is unclear whether this one single-arm trial provides evidence of clinical benefit in the treatment of SR-aGvHD in pediatric patients. Furthermore, it is unclear if the durability of response requires continued infusions of remestemcel-L. Finally, the relevance of the two previously conducted randomized, double-blind, placebo-controlled, multicenter studies that failed to meet their primary efficacy endpoints is uncertain.

The primary endpoint results in MSB-GVHD001 were statistically significant, the measured response was durable (median 54 days), and the study results were consistent across subpopulations and secondary efficacy endpoints.

Does the fact that study 265 and Study 280 were conducted over ten years ago impact how they should be considered in this context?