There is a few people excited out there - including me ! Teffific announcement today by the Blaster ... its worth going back and reading the CHF ASX update on 18th April 2018.
Following is the recent Bioworld article.
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September 24, 2018 Mesoblast poised to file BLA after clearing final clinical hurdle in phase III GVHD pediatric stem cell trial
By Tamra Sami, Staff Writer
PERTH, Australia -- Australian stem cell therapy company Mesoblast Ltd. is on its way to filing a BLA for its allogeneic mesenchymal precursor cell therapy that showed strong survival rates in children with acute steroid-refractory graft versus (aGVHD) host disease at six months.
The company reported in February that the phase III remestemcel-L trial met the primary endpoint, showing an overall response rate of 69 percent compared to a historical response rate of 45 percent at day 28 of treatment (p=0.0003).
The 180-day survival data is an “important regulatory and commercial endpoint,” Mesoblast CEO Silviu Itescu told BioWorld, explaining that the FDA wanted to see survival data at 180 days, and with that data now in hand, “there are no other clinical hurdles at this point.”
Itescu said the overall response rate needed to be statistically superior to the 45 percent historical control rate for children who had bone marrow transplants and developed aGVHD.
This data is really “important to us – there were no surprises -- but it was what the FDA had put out as being the critical secondary endpoint, and it’s where most drugs that have tried to treat this disease have fallen over,” he said.
The FDA specifically wanted this study done to ensure that it was a clean study where these children hadn't been offered any other drugs, so it's first-line therapy," he said in an earlier interview. (See BioWorld, Feb. 23, 2018.)
The results are a milestone not only for Mesoblast, but also for the regenerative medicine field.
Leading the pack
The company’s goal is for remestemcel-L to be the first commercially manufactured allogeneic cellular therapy available in the United States. Currently, there are no approved treatments for aGVHD in the U.S. The stem cell therapy already has fast track and orphan designation.
Mesoblast anticipates holding a pre-BLA meeting with the FDA in the coming months, and then it would commence filing a rolling BLA.
Mesoblast’s open-label phase III trial enrolled 55 children between the ages of six months and 17 years with steroid-refractory aGVHD at 32 sites across the United States, with the vast majority (89 percent) suffering from the most severe form of aGVHD (Grade C/D).
In patients who had a positive overall response to treatment with remestemcel-L at Day 28, survival was 87 percent at Day 100. At Day 180, survival in these patients was 79 percent (p=0.001 by Kaplan-Meier survival estimates compared to non-responders). Overall Day 180 survival for the entire remestemcel-L treated group was 69 percent.
Historical survival rates in patients with Grade C/D disease and failure to respond to steroids have been only 10 percent to 30 percent, according to Mesoblast.
These 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.
"These children are a very challenging patient population as they suffer from a particularly aggressive and life-threatening disease for which there are currently no available treatments," said lead investigator Joanne Kurtzberg, director of the Pediatric Blood and Marrow Transplant Program at Duke University Medical Center.
"We are now seeing that children who receive remestemcel-L can have significant overall response rates and reduced early mortality."
Roughly 12,000 bone marrow transplants are conducted each year in the U.S., and about half of those patients will develop GVHD, and one-fourth of all patients who receive transplants are children.
Once the pediatric indication is approved, Mesoblast will discuss with the agency what a confirmatory trial in adults would look like.
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. Japan reimbursement is about $195,000 per patient, Itescu said, noting that Japan generally reimburses at about 60 percent compared to the U.S.
The product has “outperformed our expectations,” Itescu said, noting that JCR is “doing a great job in penetrating the addressable market.” He said that uptake indicated that clinicians have no problem in using the treatment and adapting to a disease that doesn’t have other alternatives.
“They’re seeing the same kind of efficacy that we saw in the pre-approval stage, and all that bodes very well for the U.S. market,” he said.
He anticipates that the Japan data as well as the 180-day survival data will support the BLA.
Heart failure trial to report in coming weeks
Mesoblast currently 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.
The FDA granted MPC-150-IM breakthrough therapy designation for the end-stage indication under the regenerative medicine advanced therapies (RMAT) designation under the 21st Century Cures Act.
The next trial to report is the larger end-stage heart failure trial, which Itescu said is expected to report in the coming weeks. Mesoblast previously reported that interim phase III data met the primary endpoint.
A phase III trial in chronic low back pain due to intervertebral disc degeneration is also underway. Mesoblast had reported data from a phase II trial in December 2017 that showed a single intradiscal injection of 6 million mesenchymal precursor cells (MPC-06-ID) resulted in meaningful improvements in both pain and function that were durable for at least 36 months. (See BioWorld, Dec. 19, 2017.)
Itescu said the stem cell therapy is seeing "consistency in terms of multiple indications with durable outcomes in RA [rheumatoid arthritis] and disc diseases."
In each of those diseases, MPCs are thought to be activated by signals in the damaged tissues to release factors that both inhibit damaging inflammation and induce a pro-reparative state.
“We’re a long way ahead of any competitors,” Itescu said.
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GLTAH.
MSB Price at posting:
$1.87 Sentiment: Buy Disclosure: Held
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