Australian biotech Mesoblast has had a rollercoaster ride working toward FDA approval of its mesenchymal cell therapy product remestemcel-L. They are seeking approval for use in patients with graft-versus-host disease (GvHD).
More specifically, it is intended for pediatric patients with steroid-refractory acute graft versus host disease, or SR-aGVHD. This is a serious condition and new treatment options are urgently needed.
Could remestemcel-L help through an immunomodulatory function? Trial data so far have been encouraging. However, Mesoblast just announced that the FDA has determined more data are required. In fact, a whole new trial is needed, which is bad news for Mesoblast. It’s going to be time consuming and costly.
How did we get here? First a little background.
Background on remestemcel-L
Remestemcel-L is a mesenchymal cell or MSC product. It is intended to have useful immunomodulatory activity such as reducing harmful immune cell function. Mesoblast is testing it for several health conditions.
Since it is from a donor it is allogeneic and hence not the patients’ own cells. As an off-the-shelf product, it could treat large numbers of patients, which is a big plus.
It was previously called Prochymal. Now it is called Ryoncil.
Mesoblast originally acquired the MSC program from Osiris almost exactly a decade ago.
FDA wants Mesoblast to get more data
It’s been a long road since.
While Mesoblast’s MSC product has been approved for GvHD in other countries, US market approval would be a key step forward.
After an earlier rejection of a BLA submission request, this March the FDA gave a nod to Mesoblast’s BLA proceeding. The company had submitted additional data to the agency. At that point the FDA presumably began reviewing the BLA and new data. There was hope of an approval.
The deadline or PDUFA date for an FDA decision was yesterday, August 2, 2023, six months after the earlier nod.
Shift to adult GvHD focus?
Now a day later Mesoblast announced the bad news today. From the PR:
“the US Food and Drug Administration (FDA)…requires more data to support marketing approval. To obtain the data required, Mesoblast will conduct a targeted, controlled study in the highest-risk adults with the greatest mortality. This adult study is in line with our overall commercial strategy, which envisioned a sequenced progression from pediatric to adult SR-aGVHD indications. Adults comprise 80% of the SR-aGVHD market.”
I’m a little unsure why they are going to do an adult trial when I thought the earlier focus was pediatric. Maybe that will become clear and if so I’ll do an update. Does this mean they will focus just on adult GvHD moving forward? Then circle back perhaps in the future to kids?
This post is kind of a hot take on this breaking news so I may make other updates to it as well.
Had it gone the other way, this would have been the first U.S. approval of an MSC product and I believe the first approval of any off-the-shelf cell therapy in the U.S. It’s disappointing news.
Even so, the company appears committed to continuing the process and getting more data. I hope they get there.
The number of failures of MSCs in clinical trials is estimated at more than 1000. There are 4,500 listings for stem cell therapy trials on Clinicaltrials.gov. None has been approved by the FDA. It may be time to start thinking of doing something else.