For the past two years, US patients requiring transcatheter aortic valve implantation (TAVI) have had a choice of precisely one device: Edwards Lifesciences’ Sapien. Medtronic is eager to contest this market, and results of the pivotal trial of its CoreValve device, to be presented on October 29, will show how good its chances of approval are.
The bar for approval has been set by Sapien, so CoreValve will have to at least equal its performance to get the nod from the FDA when a decision is made in 2014. But to take share from the monopolist, Medtronic will have to give doctors a reason to switch. Medtronic will be looking for a clear advantage in terms of safety or efficacy or both.
Echoing the structure of Sapien’s pivotal US trial, CoreValve is being tested in two populations – patients at high risk of complications from open valve surgery and those at extreme risk, who are essentially inoperable. Extreme risk data will be presented at the Transcatheter Cardiovascular Therapeutics (TCT) meeting in San Francisco, it naturally being easier to gain approval in this group.
Results from the 358-patient extreme risk cohort in Edwards' Partner study, presented at TCT 2010, were electrifying. At one year, the overall survival rate was 69% in the Sapien group, compared with 49% in the control group, who had been treated with other non-surgical techniques such as balloon valvuloplasty.
The co-primary endpoint of death plus repeat hospitalisation was much lower in the Sapien group at 42.5% compared with 71.6% for the medical therapy group. Rates of complications including stroke were higher in the Sapien-treated patients at 30 days, but by one year had largely settled down.
US approval for extreme risk patients followed two years later (Therapeutic focus – Transcatheter aortic valves boosted by guidelines, October 1, 2012). When it comes to devices implanted wholly within the heart, the FDA is nothing if not cautious.
Second to market
High as this bar is, it is quite possible that CoreValve will clear it. According to Health Canada’s report when it approved CoreValve in January, data from three post-marketing registries – a European registry called Advance, an Italian study and a European and Canadian registry – put one-year overall survival of CoreValve-treated extreme risk patients at 68%, 78% and 79%, respectively.
In recognition of the far better survival rates with TAVI compared with medical treatment, the FDA has ruled that the CoreValve trial could dispense with a control arm.
On the safety side, stroke rates, bleeding and vascular complications were lower with CoreValve than those seen with Sapien, but new pacemaker implantation rates were higher.
The stroke rate is key, as the primary endpoint for CoreValve’s trial is slightly different to that of Sapien’s: it is all-cause death or major stroke at 12 months. The equivalent rate for this in Partner was 35%, compared with 51% in the medical management arm.
If CoreValve’s performance matches that of Sapien, US approval would seem likely. But the overall survival rate will have to be closer to the higher rates seen in the post-marketing trials – 80% would be nice – if it is to gouge a share from the sole occupier of the US market.
|Pivotal US trial of Sapien (Partner)
|Pivotal US trial of CoreValve
To contact the writer of this story email Elizabeth Cairns in London at firstname.lastname@example.org or follow @LizEPVantage on Twitter