Two years ago Medtronic bought the stealth-mode transcatheter mitral valve maker Twelve, after which it went equally quiet about the valve development programme. No longer: data from a pilot trial of the device, since named as Intrepid, was presented last week and Medtronic is confident of a world-first approval next year. And being the first entrant could be crucial given the potential size of the market.
“It could be that the mitral valve market is two to three times the one for aortic valves,” says Pieter Kappetein, the chief medical officer of Medtronic’s coronary & structural heart unit. “It depends on which patients qualify for the device and clinical considerations when you implant the valve.”
Medtronic pounced on Twelve during 2015’s mitral valve feeding frenzy, in which several other major cardiovascular players also acquired mitral valve start-ups: Edwards bought Cardiaq; Abbott bought Tendyne; Heartware bought Valtech; and Boston Scientific took an option to buy Mvalve – all in the space of three months (Boston arrives late to the mitral valve party, October 9, 2015).
“The design of the valve is more or less the same as when we acquired it from Twelve,” Mr Kappetein says, although Medtronic has been working on adapting its delivery method from transapical – which necessitates a thoracotomy and cutting through heart muscle – to the less traumatic transfemoral route, used for almost all catheter-mounted aortic valves. The transfemoral version ought to be ready for human trials in 2018.
No small feat
The new data, reported at the TCT meeting in Denver last week, concern the first 50 patients in a European and US pilot study. The 30-day mortality rate with Intrepid was 14%, and at one year follow-up in 17 of the patients this rose to 24%. All four of the deaths occurred in the first six months.
There was no device malfunction, haemolysis or thrombosis and mitral regurgitation – the condition Intrepid is intended to treat, where the valve does not close properly, allowing blood to flow back into the left atrium – was mild or absent in all survivors.
Medtronic’s Intrepid valve
“With this new technology we demonstrated feasibility, and that it results in correction of mitral regurgitation and symptom improvement,” Dr Paul Sorajja of the Minneapolis Heart Institute, the leader of the trial, tells EP Vantage. “It’s no small feat given the technical challenges of this therapy and the device development that’s required.”
The pilot trial has since enrolled a further 32 patients. Full results are expected next year, and Medtronic will need outcomes data on at least 70 patients in order to obtain CE mark. European approval ought to come in the first half of next year, Mr Kappetein says, enabling Medtronic to have the first transcatheter mitral valve on sale anywhere in the world. The event will trigger a $50m payment to Twelve’s former owners (Medtronic enters mitral valve race with obscure $400m buy, August 26, 2015).
With the process of obtaining CE mark under way Medtronic is looking towards the US. It started a pivotal US trial, Apollo, last month. Apollo might give a better idea of the exact benefit of Intrepid since it contains a control group of patients who will receive surgical valve replacement.
“There are two parts of the pivotal trial. The randomised part will randomise 650 patients against surgery, and the registry will consist of 550 patients,” Dr Sorajja says.
One arm of the study will aim to show Intrepid’s noinferiority to conventional surgery, whereas the other will recruit patients who are too sick to undergo surgical procedures.
The primary endpoint in both cohorts is a composite rate of all-cause mortality, all stroke, reoperation or reintervention and cardiovascular hospitalisation at one year. Secondary measures will concern quality of life and the valve’s performance, including its ability to correct regurgitation.
“The technology is being studied in a field in which there are no proven therapies besides medicines to improve patient outcomes,” Dr Sorajja says. “Medicines and cardiac resynchronisation devices and the like have been shown to improve survival but surgery, treating these patients with heart failure and mitral regurgitation, has not been shown to be beneficial for improving survival.”
Dr Sorajja says that there is unlikely to be a trial directly comparing Intrepid with drug treatment.
One way and another the competitive landscape is looking pretty good. Edwards’ Cardiaq valve has run into trouble, with a trial being placed on hold earlier this year. Little more has been heard on Cardiovalve and Mvalve's technology. Only one other company appears to be seriously in the running.
“Our main competitor is Tendyne,” says Mr Kappetein. “There are many more smaller companies that are also trying to come up with a replacement or repair device but they are not as far as we are, and Tendyne is the closest behind us.”
Data on the Tendyne valve, which is now owned by Abbott, were also presented at TCT. Of 30 patients who received the valve, five died within a year of implantation, giving a mortality rate of 17%. This was lower than Intrepid’s 24% rate, but the trials are not comparable, not least because they enrolled patients with different types of mitral regurgitation.
The Apollo trial will take years to report so FDA approval for Intrepid is some way off, but Medtronic is still the frontrunner in the race to the US – just as it is in Europe.