Mesoblast finally pushes GvHD cell therapy over finish line

At its third attempt, Mesoblast has secured FDA approval for Ryoncil as a treatment for children with graft-versus-host disease, the first-ever approval for a mesenchymal stromal cell (MSC) therapy in the US.

The regulator has cleared Ryoncil (remestemcel-L) to treat steroid-refractory acute GVHD in paediatric patients aged two months and older. It is derived from MSCs harvested from the bone marrow of healthy adult human donors.

Steroid-refractory acute GvHD is a serious and life-threatening condition that can occur as a complication of donor haematopoietic stem cell transplantation (HSCT), used to treat blood cancers and other disorders.

It is caused by over-stimulation of inflammatory cytokines, which causes the donated immune system to attack the patient's own body with "significant, wide-ranging health consequences, including damage to multiple organs, reduced quality of life and risk of death," commented Nicole Verdun, director of the Office of Therapeutic Products in the FSA's Centre for Biologics Evaluation and Research (CBER).

Ryoncil's approval marks the end of a mammoth journey for Australian biotech Mesoblast, which saw two earlier marketing applications for the MSC therapy turned down by the FDA in 2020 and 2023 – the first rejection coming against the advice of the agency's expert advisors.

Mesoblast ran an additional clinical trial to support its latest application, which revealed that in 54 paediatric patients with severe, acute GvHD, Ryoncil treatment achieved a complete response in 16 (30%) after 28 days, with another 22 (41%) having a partial response.

There are around 10,000 HSCTs carried out in the US each year, with the numbers rising fast as a result of improved supportive therapies that have made the procedure safer, and around 1,500 procedures are carried out in children.

It is estimated that acute GvHD occurs in approximately half of HSCT patients, and half of those cases do not respond to treatment with steroids, the standard first-line treatment. In patients who don't respond to steroids, the death rate can be as high as 70% within 100 days.

In October, Nasdaq-listed Mesoblast issued $50 million in convertible notes to top up funding in anticipation of the FDA decision to fund the launch of Ryoncil. Shares in the company were up over 50% after news of the approval emerged.

The Melbourne-based biotech held a webcast earlier today to update investors on its launch plans for Ryoncil in the US. Chief executive Silviu Itescu said on the call that Ryoncil would be available in the "coming weeks" and has a couple of years' worth of inventory on hand. He was a little coy on pricing, saying that it would be in line with other cell-based therapies that deliver long-term clinical benefits.

The company is also developing MSC therapies for other indications, including adult GvHD, inflammatory bowel diseases, heart failure, and chronic lower back pain due to degenerative disc disease.

Analysts have previously suggested that Ryoncil could make sales of $500 million-plus in paediatric and adult GvHD, with its follow-on MSC products in heart failure and disc repair potential blockbusters.