“We’re the only company in the world that has completed a study in mesenchymal stem cells derived from induced pluripotent stem cells,” he said, adding that the phase III trial puts Cynata ahead of the pack.
“The unusual thing about this program is that it’s actually not our trial; it’s being sponsored by the University of Sydney. That’s why the NHMRC is financing it, which is the peak funding body for research and development in medicine in Australia.”
Because Cynata had compelling safety and efficacy data from a phase I study in graft-vs.-host disease (GVHD), it was prepared to launch a phase II study in osteoarthritis. The principal investigator, David Hunter, had strong evidence that a good MSC product could be effective in osteoarthritis, “and you put the two together and suddenly you have a phase III trial.”
Australia’s Therapeutic Goods Administration (TGA) has confirmed that the phase III trial of CYP-004 can be conducted under the notification-only CTN scheme, which requires submission of a notification to the TGA, as opposed to the formal review and approval process required under the CTX scheme.
Macdonald said the trial all came about through a longstanding interest of Hunter, who is an orthopedic surgeon in Sydney and who has been investigating the potential utility of mesenchymal stem cells in osteoarthritis.
“He has always been challenged by the variability of the products he gets his hands on, and this product inconsistency is the major impediment ultimately to the commercialization of MSCs,” Macdonald said.
“Because Professor Hunter had been using all sorts of different products from different sources, he was ending up with different results, because the products come from different donors.”
Other researchers have complained about variability in results due to the inconsistency of other MSC products, he said, and Hunter approached Cynata because he “believed our product was the gold standard in MSCs” and could prove whether they work in osteoarthritis.
P1 was in SR-aGvHD, a world-first for an iPSC-MSC company sponsored trial and only a few months after Takahashi's world-first iPSC trial (physician-led).
Here's an interesting article from 2021 with a few additional quotes, adding more colour to the above:
Professor Megan Munsie, deputy director of Melbourne University’s Centre for Stem Cell Systems and head of engagement, ethics and policy at Stem Cells Australia, said this is the first substantial trial she has seen testing a stem cell therapy for OA.
Until now, there just hasn’t been enough legitimate clinical research to advise patients what the options are or to combat unchallenged marketing from dubious stem cell clinics, she said.
Recent meta-analyses have suggested that stem cell treatments for knee OA can relieve pain and improve physical function with no severe adverse effects. However, therapies were inconsistent, the evidence poor, trials likely to be biased, and the longevity of observed effects not guaranteed.
Part of the problem has been the variety of stem cells used previously, the different dosages and treatment intervals tested, and the assortment of manufacturing processes.
Most interventions trialled have used the patients’ own cells, called autologous stem cells, which are most often isolated from a patient’s fat and reinjected into the joint. But these products are not much more than a crude cellular resuspension, Professor Munsie said.
What sets this new trial apart, Professor Munsie said, is the novel strategy developed by Cynata Therapeutics which yields a “well-defined product”.
Their process uses stem cells originally derived from the bone marrow of one young donor and expanded to generate a consistent product at scale. As such, “every patient [in the treatment group] is going to receive the same thing, taking one of the uncertainties out of the picture,” Professor Munsie said.
Cynata has already tested a similar stem cell therapy (produced by the same method but still, as yet, unapproved) in another clinical trial for graft-versus-host disease, which showed they can produce a safe cellular product, Professor Munsie said.
Safety aside, efficacy is another question.
Although the use of stem cells in osteoarthritis is still considered experimental, Professor Hunter said there’s now good evidence to suggest mesenchymal stem cells work by modulating the immune response and reducing destructive inflammation within the joint, which could help facilitate the body’s own mechanisms for cartilage repair.
“By virtue of reducing that inflammation and allowing the joint’s known innate capacity for repair to take over, we would hope to at least slow some of the structural change that’s going on within the joint,” Professor Hunter said.
Outcome measures include physical assessments to assess patients’ functional performance, along with three MRI scans measuring cartilage thickness to see whether stem cells slow down cartilage loss or aid repair.
Patient-reported outcomes of pain intensity, physical activity and quality of life will also be assessed, and the proportion of patients achieving a ‘patient-acceptable’ level of knee pain at 24 months is a primary outcome for the trial.
Here is what I appreciate the most about Professor Hunter being in charge (and not the company):
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