Mesoblast lifts off as FDA agrees to review GvHD drug again

More than two years after Mesoblast was poleaxed by the FDA’s rejection of its mesenchymal stem cell therapy for children with graft versus host disease (GvHD), the US regulator has started a second priority review of the drug.

The therapy – called remestemcel-L – is used to prevent the life-threatening complication, which can affect children who receive bone marrow transplants for serious blood cancers and some other conditions. It occurs when the transplanted cells mount an immune response against the patient’s tissues.

In 2020, the FDA said it would not approve remestemcel-L, going against the recommendations of its own expert advisors, and asked the company to provide more evidence of efficacy.

That decision was a massive disappointment both to Mesoblast and medics caring for paediatric bone marrow transplant patients, as there are no approved therapies for GvHD in the under 12-years age bracket for patients who don’t respond to steroid therapies.

Shares in the Australian biotech rose 14% in the wake of the announcement that US approval may be back on the table, with the regulator now scheduled to deliver a verdict on remestemcel-L by 2nd August.

There are around 50,000 bone marrow or haematopoietic stem cell transplants (HSCTs) carried out around the world each year, with the numbers rising fast as a result of improved supportive therapies that have made the procedure safer.

If treatment with steroids doesn’t work to limit the immune reaction, which is estimated to occur in up to 15% of cases, the death rate can be as high as 70% within 100 days.

If approved, remestemcel-L will be the first allogeneic or “off-the-shelf” cellular medicine to be approved in the US, according to Mesoblast. So far, all cell therapies are based on cells harvested from patients themselves.

The company bolstered its marketing application for the refiling with long-term survival results through at least four years for children enrolled in its phase 3 trial, new outcome data in high-risk patients, and testing showing that an assay for potency accurately reflects the activity of the treatment – something that had been called into question by the FDA.

Updated results with the therapy show that two-thirds (67%) of high-risk children treated with remestemcel-L responded positively to treatment within 28 days and were alive after 180 days compared to just 10% of historical controls taken from patient registry data.

The therapy is already approved as Temcell in Japan, where it is licensed to JCR Pharma and generates a couple of million dollars per quarter for Mesoblast. Sales have previously been predicted by analysts to reach upwards of $150 million per year in paediatric GvHD, if approved in the US and depending on pricing.

“Over the last two years we have worked tirelessly to address the issues previously raised by the FDA,” said Mesoblast's chief executive, Silviu Itescu. “We look forward to working closely with the agency over the review period with the aim to make remestemcel-L available.”