FDA rejects remestemcel-L for the treatment of steroid-refractory aGvHD pending further study

In a surprise move, the U.S. Food and Drug Administration (FDA) have issued a complete response letter rejecting the application of a Biologics License Application for remestemcel-L for the treatment of pediatric steroid-refractory acute graft-versus-host disease (SR aGvHD).¹ At least one additional randomized clinical trial in adults or children will need to be performed before the company can refile for approval. This decision was taken despite the Oncologic Drugs Advisory Committee (ODAC) of the FDA voting nine to one that remestemcel-L safe and effective. This was reported on by the GvHD Hub and can be found here.

The FDA felt that there is still a need to improve specific tests to assess the biological activity of remestemcel-L, and show that the ability of remestemcel-L to reduce inflammation in humans can be confirmed by inflammatory biomarkers. In the absence of these results, the FDA raised concerns that the manufacturing process could not consistently produce the necessary quality of the drug product. It is expected that the company will request a Type A meeting with the FDA to ask for an accelerated approval following the completion of the requested clinical trial.

The decision to approve remestemcel-L by the ODAC was based on the results of the prospective MSB-GvHD001 study (NCT02336230), which tested 55 pediatric patients with SR aGvHD and recorded overall response rates of 70.4%. Further details of this study can be found here on the GvHD Hub. In addition to its use in GvHD, remestemcel-L is currently being evaluated in a phase III trial (NCT04371393) for acute respiratory distress syndrome in 300 patients with COVID-19.

Remestemcel-L uses mesenchymal stem cells from the bone marrow of unrelated donors as an allogeneic cell therapy product. It has potential immunomodulatory effects and may be able to counteract elevated cytokine release by downregulating inflammatory responses.