Pictured: Hand making a rejection stamp on a stack of papers/iStock, Pavel Muravev
The FDA has rejected Mesoblast Limited’s application for its investigational immunomodulator remestemcel-L, which it was proposing as a treatment for pediatric steroid-refractory acute graft versus host disease, the company announced Friday.
In its Complete Response Letter (CRL), the regulator asked for more data in adult patients before reconsidering the application. To fulfill this requirement, Mesoblast is planning to conduct a controlled study in the most at-risk adults with the highest rates of mortality.
Company shares tanked 66% in premarket trading in response to the news.
Nevertheless, the FDA’s rejection letter raised “no safety issues across more than 1,300 patients who have received remestemcel-L to date,” Mesoblast CEO Silviu Itescu said in a statement, adding that the regulator also did not flag concerns with its manufacturing process and even acknowledged improvements in the potency assay that the company used to assess the candidate.
Mesoblast will have a Type A meeting with the FDA in 45 days to discuss the trial design for the planned adult study.
According to Mesoblast’s announcement, it had already been making preparations to launch an adult study for remestemcel-L even before the CRL, in line with its commercial strategy of eventually pushing the candidate into adult patients, who comprise 80% of the steroid-refractory acute graft versus host disease (SR-aGVHD) market.
Existing treatments have so far failed to substantially improve outcomes in adult patients with the highest mortality risk, and 90-day survival has stagnated between 20% and 30%, according to the company’s news release.
Friday’s rejection is remestemcel-L’s latest regulatory roadblock. Mesoblast first tried for an approval in May 2019, presenting clinical data that showed high rates of treatment response and patient survival. Mesoblast also won the FDA’s Oncologic Drugs Advisory Committee strong support in August 2020, when the panel voted 9–1 in favor of an approval.
Nevertheless, the FDA delivered a surprise rejection in October 2020, raising the need for at least one more randomized controlled study in order to generate more evidence of remestemcel-L’s efficacy.
In Mesoblast’s resubmission, which the FDA accepted in March 2023, the company included long-term survival findings through at least four years, as well as outcome data for high-risk patients. Before the resubmission, the regulator had also completed its Pre-License Inspection of Mesoblast’s manufacturing facility and found no issues.
Derived from the bone marrow of an unrelated donor, remestemcel-L treatment uses culture-expanded mesenchymal stromal cells to suppress pro-inflammatory cytokines, while also enhancing the body’s anti-inflammatory response. This modulates the immune response that otherwise would give rise to SR-aGVHD. Remestemcel-L is approved under the brand name Ryoncil inother territories, including Canada and New Zealand.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
