For the past five years the market for transcatheter aortic valves has been a duopoly, split between Edwards Lifesciences’ Sapien and Medtronic’s CoreValve franchises. Abbott Laboratories, usually such a strong player in vascular tech, has trailed badly. But it could soon start gearing up to get itself a slice of the action.
European post-approval data reported this week on Portico, the aortic valve Abbott inherited from St. Jude Medical, are positive. More importantly the valve’s US pivotal trial is due to report in the next couple of months, and will have to match the superb results seen with the approved devices.
Results from the 941-patient Portico-1 registry, presented last week at the TCT meeting in San Diego, showed that a year after implantation 12.1% of Portico recipients had died. Rates of cardiovascular mortality, disabling stroke and heart attack were 6.6%, 2.2% and 2.5% respectively. The proportion of patients classified with NYHA class III or IV heart failure fell from 63.8% to 7.7%. The rates of mortality and stroke in particular were low, the authors wrote in the Journal of the American College of Cardiology.
All of which is great, but doesn’t get Abbott any further ahead in the US, Portico-1 having been conducted in other countries. As far as the US is concerned Abbott must wait until its pivotal trial reports towards the end of this year. This study will enrol more than 750 patients and is, like pivotal trials for Sapien and CoreValve, split between patients at high risk of complications and death from surgery and those at extreme risk, who are essentially inoperable.
Sapien and CoreValve were approved on the basis of vastly improved survival compared with a surgically implanted valve in high-risk patients and with drug therapy in the extreme risk group. Portico will not face these tests. Since there are now commercially available transcatheter valves it would be unethical to deny them to the control group, so Portico will go up against Sapien and/or CoreValve.
|US pivotal trials vs drugs or surgery|
|Pivotal trial ID||NCT00530894||NCT01240902|
|Extreme-risk endpoint(s)||Death: 31% vs 51% for best care
Death or repeat hospitalisations: 43% vs 72% for best care
|Death or major stroke: 26% vs prespecified goal of 43%|
|High-risk endpoint(s)||Death: 24% vs 27% for surgery
Death or repeat hospitalisations: 35% vs 36% for surgery
|Death: 14% vs 19% for surgery|
|All endpoints at 1 year. Source: clinicaltrials.gov, company communications.|
A direct comparison of trial data with these three valves is thus impossible. But another valve, as yet unapproved, could provide a template.
Valves vs valves
The US pivotal trial of Boston Scientific’s Lotus reported data in May 2017, but the company has delayed an approval bid until it fixes a flaw with the valve’s delivery system (Boston has trouble delivering its valve, November 29, 2017).
Delivery problem or not, the device’s US pivotal trial was widely taken as positive. Lotus was shown to be non-inferior to controls – Medtronic’s CoreValve and a follow-on device, CoreValve Evolut – on safety and beating them on efficacy (Lotus blooms in phase III, May 16, 2017). Whether this is approvable will not become apparent until next spring at the earliest.
|US pivotal trials vs other transcatheter valves|
|Pivotal trial ID||NCT02202434||NCT02000115|
|Safety endpoint||30-day composite of death, stroke, life-threatening and major bleeds, stage 2 or 3 acute kidney injury or major vascular complications||30-day composite of death, disabling stroke, life-threatening bleeds requiring transfusion, acute kidney injury requiring dialysis or major vascular complications|
|Safety finding||17% vs 20% for CoreValve (noninferior)||TBA|
|Efficacy endpoint||1yr composite of death, disabling stroke or moderate or greater paravalvular aortic regurgitation||1yr composite of death or disabling stroke|
|Efficacy finding||16% vs 26% for CoreValve (superior)||TBA|
|Source: clinicaltrials.gov, company communications.|
If Lotus does get approved on this data, the bar Portico will have to clear in its pivotal study will be made manifest. With three aortic valves already on the market, however, its commercial chances will be harder to predict.