REMESTEMCEL-L

Does Mesoblast's Remestemcel-L Have A Blockbuster In The Bag?...Written by Slingshot Contributor: Phil Loria

Evaluating Mesoblast's recent data on remestemcel-L (MSC-100-IV) as pivotal trials begin in 2016. Can the drug receive approval and become standard of care?

Mesoblast also had a huge week with shares up 22% Monday after theyreleased positive results from a study of children with acute graft versus host disease (aGVHD) following a bone marrow transplant (BMT). They alsoannounced Wednesday that their licensee in Japan, JCR Pharmaceuticals, launched remestemcel-L (under the name TEMCELL) for the treatment of aGVHD, making it the first fully approved cell therapy in Japan. The Japanese Government's National Health Insurance set the price of TEMCELL at approximately $7,700 per bag of 72 million cells, meaning a typical adult treatment course costs from $123,000 to $185,000. Mesoblast will receive royalties and other payments from JCR at predefined thresholds of cumulative net sales. Mesoblast is currently conducting a 60-patient, open label Phase III trial, and could start regulatory filings in 2017. With the drug already approved in Japan and data showing positive signs, some investors believe Mesoblast is on the way to having its first FDA-approved drug. Positive Phase III results and starting the regulatory process in the US could be huge value drivers over the next year, and biotech investors should definitely have Mesoblast on their radar.
Patients who receive a bone marrow transplant are susceptible to attacks from donor cells that cause aGVHD, which activates pro-inflammatory T-cells causing sometimes fatal tissue damage in the skin, gut and liver. According to the Center for International Blood and Marrow Transplant Research, there are about 30,000 allogeneic BMTs globally per year for diseases including hematological cancers, with 25% of all cases in the pediatric population. Nearly 50% of all allogeneic BMT patients develop aGVHD. Liver or gastrointestinal involvement occur in up to 40% of all patients with aGVHD and are associated with the greatest risk of death, with mortality rates of up to 85%. There are currently no approved therapies for aGVHD patients in U.S, and off-label options have demonstrated mixed efficacy with high toxicity.
If remestemcel-L is as effective and safe as Mesoblast claims, the drug should do well in Phase III trials and fair well in the regulatory process. Our interview will try to break down the data to see if aGVHD experts agree with Mesoblast on remestemcel-L's potential. If experts are confident in the drug's efficacy, chances of approval, and ability to win the market, it could signal big movements for MESO in the near future. Here are some questions I'd like to ask.
Questions for an expert with experience treating patients for aGVHD following an allogeneic bone marrow transplant, who has a deep knowledge of Mesoblast's various trials for remestemcel-L. He or she will also have a general knowledge of other treatment options and regulatory processes.

1. How many sufferers are identified and realistically seeking treatment in your practice today, and how do you treat them?
2. According to the Center for International Blood and Marrow Transplant Research, there are about 30,000 allogeneic BMTs globally per year for diseases including hematological cancers, with 25% of all cases in the pediatric population. Nearly 50% of all allogeneic BMT patients develop aGVHD. Liver or gastrointestinal involvement occur in up to 40% of all patients with aGVHD and are associated with the greatest risk of death, with mortality rates of up to 85%. To your knowledge, are these accurate epidemiological estimates of the patient population?
3. What are the costs of current therapies? Will remestemcel-L have a higher cost than current therapies?
4. An overall response rate of 65% was seen at day 28 after treatment with MSC-100-IV. A response rate of 81% was seen when MSC-100-IV was used as front-line therapy following steroid failure. Could this suggest that remestemcel-L will be used specifically as a front-line therapy following steroid failure, or does the overall response rate of 65% warrant usage for the whole patient population?
5. In patients with gastrointestinal and liver disease, who have the highest mortality risk, overall response rates were 65% and 62% respectively. Are these rates sufficient in your opinion to warrant widespread usage for this subset of patients?
6. Children who achieved overall response at day 28 had significantly improved survival (82% vs 39%, log rank p-value <0.0001). Extending therapy beyond day 28 in children who had not achieved an overall response, but had some improvement at day 28 resulted in significantly improved survival (72% vs 18%, log rank p-value 0.003). Can you discuss the relevance of these results?
7. To support filing of a biologic license application to the United States Food and Drug Administration for regulatory approval, Mesoblast is conducting a 60-patient, open label Phase III trial using MSC-100-IV as front-line therapy in children with steroid-refractory aGVHD. What are important things to look for, or potential problems that could arise in the Phase III trial?
8. How do you see the patient population changing in the future? Are there possible improvements in BMT technology that could reduce the number of patients who develop aGVHD following an allogeneic bone marrow transplant?
9. There are currently no approved therapies for patients with acute steroid-refractory GVHD in the United States, and off-label options have demonstrated mixed efficacy with high toxicity. How do you compare remestemcel-L to existing treatment options?
10. What are the negatives of an open label trial? Was there any way for them to not have it open label or is that necessary for the trial? Do you think the FDA will accept these results?
11. Assuming it is approved, what percentage of existing patients will use remestemcel-L? What percentage of new patients will use remestemcel-L?
12. Will this treatment increase the number of transplants in general? Are there patients currently not receiving them because of the risk of aGVHD that may not be able to?

In Conclusion

This interview will aim to develop a better understanding of Mesoblast's recent data release on remestemcel-L as they move into a 60-patient open label Phase III trial to support BLA filing. The discussion should help investors understand the market potential for remestemcel-L and future growth prospects for Mesoblast......................................Slingshot Insights will interview a Subject Matter Expert, then post a transcript and recording of the conversation..............V