The on-again, off-again European pivotal trial of Carmat’s artificial heart is back on, and the French group believes it can meet its target of CE mark approval next year. But it is actively enrolling patients in only one of the four countries in which the trial is running, and the timeline for approval is ambitious to say the least.
Carmat’s chief executive, Stéphane Piat, cannot be faulted for confidence, however. “If you compare our device to what has been achieved so far with other solutions, we are much better and we have no complications,” he told Vantage this morning at the annual meeting of the European Society of Cardiology. “We are doing much better than anything ever.”
The pivotal study is being conducted in Denmark, France, the Czech Republic and Kazakhstan, and consists of two cohorts, each of 10 patients in the very last stages of biventricular heart failure. The first arm of the trial read out in January, with a clean safety profile and seven of the 10 patients reaching the primary endpoint of six months’ survival or a successful heart transplant within that time.
This was an improvement on the group’s four-patient feasibility trial, in which only half of the patients reached the six-month time point. Carmat claims that the only other total artificial heart currently on the market – Syncardia Systems’ Total Artificial Heart – has a six-month survival rate of 54-62%.
The second half of the Carmat trial ought to match or exceed the 70% survival rate at six months seen in the first cohort, Mr Piat says.
“There is no reason why you should not expect some improvement in survival, we hope. But in terms of complications we can’t do better than 0%.”
If the data from the second cohort do match that from the first, Carmat ought to be odds-on for CE mark. But the trial has been delayed twice, most recently by a change to the manufacturing process for the prosthesis, which Mr Piat says was a planned alteration scheduled for the end of cohort one, to allow the company to improve the design of the device.
The current status of the trial is that the Danish authorities have given approval for implants to resume, and the company is in discussions with the authorities in Kazakhstan and the Czech Republic with a view to resuming enrolment there. It has not yet requested permission to restart enrolment in France.
The trial began in August 2016 and took until July 2018 to recruit the first 10 patients. Mr Piat declined to say how many patients have been signed up to the second part of the trial, but unless eight or nine implants have already been done the plan to complete enrolment by the end of this year looks tight.
“There is a shortage which is enormous, so it’s pretty easy to find patients,” Mr Piat says. “We never had anybody refuse the treatment. It should be pretty straightforward.”
If the trial does hit this timeline, the data ought to be presented in June or July 2020, and the company plans to submit its CE mark application to the German notified body Dekra by that year’s end.
Mr Piat emphasises that commercial uptake of the product, should CE mark be awarded, is hard to predict, and points out that usually initial sales of a new device can be pretty slow.
“For Carmat it could be a bit different because the shortage of human hearts is so important – the demand, unfortunately, is huge. If we confirm the data we have today we might have a lot of interest.”
He adds that the reimbursement pathway in Germany in particular is very good and very quick, despite the fact that the device is expected to sell for hundreds of thousands of Euros – though Mr Piat is quick to add that heart transplantation is even more expensive, and the price of most medical devices comes down after they have been on the market for some time.
Carmat calls its device “the world’s most advanced total artificial heart project”, and this is probably true in the scientific sense. It is not true commercially; US group Syncardia has been selling an artificial heart for nearly two decades. Mr Piat regards Syncardia’s device very much as yesterday’s technology.
“Syncardia is very important in the history of artificial hearts because they proved that it’s possible, and it works, to change a human heart for a device,” he says. “But Syncardia’s is a very old technology and we are very far from what they are doing.”
He adds that Syncardia’s device has been linked with complications such as stroke, cable infection and gastrointestinal bleeding, unlike Carmat’s heart, he says.
So the product might stand a chance of competing if and when it gets to market. But there is another barrier Carmat must overcome: obtaining the cash to get that far.
The company has had a number of sources of funding over the years, including a €30m ($32.6m) loan from the European Investment Bank, obtained last December, and a €33m subsidy from the investment bank Bpifrance. But Carmat ended 2018 with a net loss of €41.7m and cash of just €25.3m. It will need around €100m to break even, according to Mr Piat.
“We burn money, we don’t earn money,” he says. No wonder the group’s timeline for approval is so brief.
|The chequered history of Carmat's pivotal European trial|
|Aug 29, 2016||Begins pivotal study|
|Nov 30, 2016||Suspends study after the first patient to receive the implant dies|
|Feb 6, 2017||Withdraws its initial request to resume the trial|
|May 2, 2017||Resumes study in France|
|Oct 5, 2017||Expands study to Kasakhstan|
|Oct 13, 2017||Expands study to Czech Republic|
|Apr 5, 2018||Performs 30% of trial implants and states aim of obtaining CE mark in 2019|
|Jul 11, 2018||Completes enrollment of cohort one|
|Jan 15, 2019||Presents positive interim results of the first part of the study and changes manufacturing process|
|May 10, 2019||Further delays production of prostheses from initial goal of April 2019|
|May 21, 2019||Resumes production of prostheses|
|Aug 28, 2019||Gains approval to restart enrolment in Denmark|
|Source: company website.|