EP Vantage Interview - Heart disease a fertile field for Mesoblast


Fresh from encouraging data in cardiac ischaemia, Australian stem cell specialist Mesoblast has the go-ahead from European authorities to begin a phase IIb trial of Revascor, its drug derived from donor bone marrow cells, in myocardial infarction (MI).

In an interview with EP Vantage, Dr Donna Skerrett, Mesoblast's chief medical officer, says one of the two major goals of the study will be to test the feasibility of the delivery of the Australian group’s therapy, which involves infusing up to 25 million mesenchymal precursor cells at the time patients undergo angioplasty.

The trial is based on data from a subset of patients in a phase II trial in congestive heart failure. This showed patients with signs of reduced myocardial blood flow who received injections of Revascor experienced improved blood flow in ischaemic heart muscle and reduced size of ischaemic tissue when compared to control patients.

“We were seeing things that translated to an improvement in cardiac function at an earlier point than we expected,” Dr Skerrett says. “They were having zero hospitalisations for decompensation; they overall had fewer cardiac deaths. That did encourage us to move forward with another clinical development programme."

That trial, launched before Mesoblast acquired sister company Angioblast last year, featured an endocardial injection of Revascor, a procedure that required patients to undergo cardiac catheterisation.

“An additional procedure to deliver the stem cells was not the appropriate thing to do in an acute heart attack study,” she says. “That’s when we started looking around and how we came upon the intracoronary infusion method combined with the standard of care.”


Mesoblast’s technology relies on its ability to enrich the mesenchymal precursor cells from bone marrow. Unlike some transplanted cells, those precursor cells carry no immunological markers and thus can be harvested from any donor. As gene therapies have disappointed in their ability to regrow blood vessels in other cardiovascular indications, researchers have been looking hopefully to cell therapies (AHA 2010 – Little hope for gene therapy in ischaemic limbs, November 17, 2010).

It is not exactly clear how the cells help repair damaged or diseased tissue: it may be that their ability to secrete paracrine growth factors and cytokines as well as decrease inflammatory and immune reactions is more important than their ability to differentiate into tissue-specific cells.

The group is not alone is pursuing an injected cell-based therapy for heart disease. California firm Cytori Therapeutics has launched its own European pivotal trial for its adipose-derived and reconstructive cell therapy in MI. The difference, of course, is that Cytori’s technology uses a patient’s own cells and Mesoblast’s are donor cells, which theoretically means a more immediate use in the case of post-MI emergency surgery, as Mesoblast has been targeting in its trial.

“Our pre-clinical studies and our understanding of the mechanism of action certainly indicate that timing is very important in acute MI settings,” Dr Skerrett says. “If you get the cells in as early as possible after the ischaemic insult they are most likely to be effective. A lot of that has to do with the ischaemic factors that are the trigger for our cells to release the paracrine factors and cytokines that start the recovery cascade.”


The Mesoblast technology has certainly inspired excitement in its partners. Cephalon offered $130m upfront and bought a 20% share of Mesoblast to secure rights to the cell technology in cardiovascular, Parkinson's, Alzheimer's and oncology indications, in addition to financing late-stage trials including the new MI trial (Cephalon closes the blast doors for a rocketing stem cell deal, December 8, 2010).

Teva is in the process of acquiring Cephalon, and will inherit the deal and Cephalon’s stake in Mesoblast in the process.

Growing expectations have transformed Mesoblast into Australia’s second biggest public pharma company by market capitalisation – behind only blood products and vaccine specialist CSL - without a single product on the market. Its shares have nearly quadrupled in the past year, giving it a market capitalisation of A$2.29bn ($2.43bn).

The Cephalon deal left Mesoblast with $263m cash on June 30, enough to enable the Melbourne-based group to advance development of the same technology to orthopaedic settings and begin research into new indications.

“We can now push ahead with spinal fusion, degenerative disc and long bone fractures,” said company spokeswoman Julie Meldrum. “We’re also in pre-clinical studies in other major indications like diabetes in which Mesoblast will retain 100% of the upside.”

Cell therapy to regrow blood vessels has yet to fully prove itself in the clinic, yet the technology's promise has already shown itself transformative for Mesoblast. Further clinical success will only build expectations, though a stumble could prove a reality check for the high-flying group.

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