PERTH, Australia –Australian stem cell therapy company Mesoblast Ltd. announced that the FDA has accepted its BLA for priority review for its allogeneic mesenchymal precursor cell therapy, remestemcel-L, for children with acute steroid-refractory graft-vs.-host disease (aGVHD).

The first module of the rolling BLA was submitted in April 2019, and the final module was submitted on Jan. 31, 2020. The FDA has set a PDUFA date of Sept. 30, 2020, for the product branded as Ryoncil.

A priority review provides a six-month review period compared to 12 months for a regular review. The product had already received fast track designation for aGVHD. Mesoblast's allogeneic candidates are based on mesenchymal lineage cells collected from the bone marrow of healthy adult donors.

The FDA said it would hold an advisory committee meeting for the remestemcel-L BLA, Mesoblast CEO Silviu Itescu told BioWorld.

Silviu Itesco, CEO, Mesoblast

“It’s a brand new technology, the first of its kind, so we expect to have an advisory committee panel, and those are typically a few months ahead of the PDUFA date. I think it’s an opportunity to get a lot of key opinion leaders to support the strength of the data,” he said.

The company reported in February 2018 that the phase III trial met the primary endpoint, showing an overall response rate of 69% compared to a historical response rate of 45% at day 28 of treatment (p=0.0003).

The FDA had requested additional 180-day survival data, which showed a survival rate of 79% compared to an expected 30% survival rate in a pediatric phase III trial in aGVHD. The open-label phase III trial enrolled 55 children with steroid-refractory aGVHD between the ages of 2 months and 17 years in 32 sites across the U.S., with 89% of patients suffering from the most severe form of the disease (grade C/D).

Those outcomes are consistent with previous results in 241 children with steroid-refractory aGVHD who failed to respond to multiple biologic agents and were treated under an expanded access program that followed outcomes through 100 days. The multi-infusion regimen in both the expanded access program and the phase III trial was well-tolerated.

Roughly 12,000 bone marrow transplants are conducted each year in the U.S., and about half of those patients will develop GVHD; one-fourth of all patients who receive transplants are children.

“There is a need to improve survival outcomes in children suffering from the more advanced stages of this devastating disease. The acceptance of the BLA represents an important milestone for the company,” Itescu said.

If approved, Mesoblast is ready to launch the product in the U.S. immediately, he added.

In November 2019, Mesoblast completed an AU$75 million (US$50.32 million) placement to gear up to launch its first stem cell product into the U.S. market. The CEO said he is planning for a sales force of 10 to 20 people who will sell the allogeneic product to 15 or so transplant centers.

The company’s manufacturing facility is based in Singapore and is owned by Lonza. Itescu said Mesoblast is looking at bringing another facility online following approval.

He said he anticipates that the same data will satisfy European regulators.

The stem cell therapy is already approved in Japan for aGVHD (branded as Temcell) in both pediatric and adult indications. It was the first allogeneic regenerative medicine to receive full approval in Japan and was launched with partner JCR Pharmaceuticals Co. Under the terms of the partnership, Mesoblast receives royalties on Temcell product sales for all licensed indications.

Mesoblast has two other stem cell therapy candidates in phase III trials. Its MPC-150-IM is in two phase III trials for chronic heart failure – one for end-stage (class IV) heart failure patients with left ventricular assist devices (LVADs) and another larger trial in advanced (stage III) heart failure.

New data on heart failure patients

On March 30, the company reported data from a subset of 70 patients with end-stage ischemic heart failure that showed a beneficial effect on LVAD weaning, major mucosal bleeding, serious adverse events and readmissions in ischemic heart failure patients.

“We get some very nice subset analysis data on the older ischemic patients in the LVAD study, showing that beyond the reduction in bleeding in the gut, they also had the ability to strengthen their heart by showing they could be weaned off their device,” Itescu said, adding that they also had a significant reduction in cardiovascular hospitalization rates.

Compared to controls, in MPC recipients the mean proportion of temporary weans from LVAD support was higher (64% compared to 43%), and the rate of mucosal bleeding was lower, and there were fewer serious adverse events.

“Given that they’re older ischemic patients, they represent the phenotype of the majority of patients in the phase III trial,” he said.

The larger end-stage heart failure trial is on track to report midyear. Mesoblast previously reported that interim phase III data met the primary endpoint.

The FDA granted MPC-150-IM breakthrough therapy designation for the end-stage indication under the regenerative medicine advanced therapies designation under the 21st Century Cures Act.

Potential COVID-19 treatment

Earlier in March, Mesoblast said it was evaluating remestemcel-L in patients with acute respiratory distress syndrome caused by COVID-19 in the U.S., Australia, China and Europe.

The company is in active discussions with various governments, regulatory authorities, medical institutions and pharmaceutical companies to implement those activities.

“What people are dying of is acute respiratory distress syndrome, which is the body’s immune response to the virus in the lungs, and the immune system goes haywire, and in its battle with the virus it overreacts and causes severe damage to the lungs,” Itescu said.

“We’re going to be evaluating whether an injection of our cells intravenously can tone down the immune system just enough so it gets rid of the virus but doesn’t destroy your lungs at the same time.

“We have now looked at our own data in lung disease in adults where half the patients had the same kind of inflammation in the lungs as you get with coronavirus, and our cells significantly reduced the inflammation and significantly improved lung function,” he said.

Headquartered in Melbourne, Mesoblast also has facilities in New York, Singapore and Texas and is listed on the Australian Securities Exchange (ASX:MSB) and on Nasdaq (MESO).

Mesoblast shares (ASX:MSB) gained slightly on the news, up 9% to AU$1.51 per share by market close April 1.