Regenerating diseased heart tissue is seen as one of the best targets for stem cell therapies, and yet with hundreds of patients, and at least half a dozen types tested, few projects have proceeded past phase II. UK-based Cell Therapy believes that it has developed a strategy to get to market.
In using mesodermal progenitor cells and focusing on patients whose heart tissue is at high risk of incomplete revascularisation, Cell Therapy has found a population that qualifies for orphan designation and will allow for speedy development and regulatory review. It also boasts a delivery system that will not require specialist training. “What we’re hoping with our stuff is that we have compelling efficacy results, but in a delivery that can fit very simply into the existing big pharma paradigm,” says the group's executive director, Ajan Reginald.
Mr Reginald sees that the interest generated in CAR-T in the past two years has perhaps paved the way for greater acceptance of advanced therapies in cardiovascular care. “CAR-T is an example where big pharma is willing to potentially change its model because it’s something that’s got compelling efficacy results.”
Cell Therapy remains largely in stealth mode as it is still funded by its original founders and has not sought any venture capital cash. But for a little-known company it has advanced significantly, with its HeartCel having completed a phase II trial in the target population.
This population has a congenital defect, bifurcation and trifurcation in their cardiac arteries, and thus might not completely recover following coronary artery bypass graft procedures – the allogeneic cells are injected into the area that cannot be revascularised during the surgery.
At the recent International Society of Stem Cell Research annual conference Cell Therapy presented 24-month data on patients treated with HeartCel, which is what the group calls its immunomodulatory cells generated from the mesodermal progenitor cells.
All of its patients are still alive at 24 months and none has suffered a major adverse cardiovascular event; the group says the cardiovascular event rate can be as high as 70% among these patients. Moreover, it has measured a reduction in the size of patients’ scars and an improvement in quality of life.
The congenital defect affects an estimated 290,000 patients in the US and Europe, Mr Reginald says, putting it well below the threshold necessary to qualify as an orphan drug. As such phase II data could be all that is necessary to gain approval in the EU, though a US-based pivotal trial will probably be necessary to gain an FDA green light. The European Medicines Agency application is expected to be submitted in 2016 with hopes for launch the following year.
But he discourages any talk of expanding HeartCel into the larger population of heart failure patients.
“HeartCel is very specifically only useful for these patients that have an inherent disposition toward incomplete re-vascularisation,” he says. “It absolutely wouldn’t work in another population."
He adds: “We’re focused on producing these products that have this critical target product profile. In this day and age you’ve got to pick populations where you think you have the most profound effect because that’s better for patients and it also gives the physician a very precise tool.”
Solo or with a partner?
For this reason Mr Reginald is enthusiastic about the potential for a solo launch, at least in Europe.
“In Europe the best way is for us to take it to market ourselves. There are about 30 specialist heart centres,” he says. “We have the expertise in house to launch products. We’re bringing on more people who have launched dozens of products and have led sales and marketing organisations across Europe. And we have the key opinion leaders interested and involved.”
The US will be different because of a greater dispersion of cardiovascular speciality hospitals as well as population, so a partnership might be necessary after approval, assuming that data from the pivotal trial are positive.
For a small company pondering a regulatory submission to have not sought at least the support of venture capital is unusual – to say nothing of seeking neither a public listing nor big pharma partnership support. However, Mr Reginald describes the group as “comfortable” with its current financial outlook.
“We’ve had discussions with VCs from day one,” he says. “The deal structures have not been ideal for the current shareholder. And we’ve got a lot of the skillsets in-house.
“As we look at the US phase III studies, we’re considering different options.”