HeartWare’s efforts to get its ventricular assist device, a type of heart pump, approved in the US on the same footing as its rival Thoratec’s competing product hang in the balance after mixed data from its pivotal trial.
On the primary endpoint, the trial is a win: HeartWare’s HVAD pump was non-inferior to Thoratec’s HeartMate II on two-year survival without disabling strokes. But the overall stroke rate – which has plagued HVAD in the past – was higher than expected and more than twice as high as in the control arm. HeartWare’s shares fell 3% yesterday to close at $84.39 as investors weighed the product’s chance of approval.
The Endurance trial is to be used to obtain FDA approval for HVAD as destination therapy – a permanent implant in patients too sick to receive a heart transplant. It is already approved in the US for temporary use, known as bridge-to-transplantation, where it is intended to be removed when a donor organ becomes available.
Thoratec’s HeartMate II is already approved in the US for both uses so HeartWare is playing catch-up.
These data are in fact from only the first cohort in the Endurance study, sometimes referred to as Endurance I. In this group 446 patients with end-stage heart failure were randomised 2:1 to HVAD or HeartMate II, with rates of stroke-free survival at two years being 55% and 57.4% respectively.
However, this only counted strokes scoring 4 or above on the Modified Rankin Score – severe strokes after which the patient is unable to walk. The combined rate of all ischaemic and haemorrhagic strokes was 31.1% with HVAD, versus 12.7% for HeartMate II.
This might not be enough of a signal for the FDA to deny approval; these patients are very ill, and a second therapeutic option would be welcome, particularly as Thoratec’s approved device has had its own problems, notably with thrombosis and its control system (Patient deaths blamed on user error, but Thoratec pump sales could fall, March 5, 2014).
But it will mean that more is resting on the second Endurance cohort, aka Endurance II, recruitment in which is 80% complete. This is intended to examine whether stricter control of patients’ blood pressure can decrease the stroke rates (HeartWare’s pivotal data controversy could affect approval – and sales, September 3, 2013).
The endpoint here is stroke incidence at one year; data on these 450 or so additional patients are expected in 2016. These results will be folded into HeartWare’s destination therapy PMA submission, pencilled in for next year.
The next generation
Thoratec, however, is not letting the grass grow: its next-generation pump, the HeartMate III, is already enrolling patients into a US approval study. This aims to prove non-inferiority to HeartMate II when it comes to survival free of device replacement and debilitating stroke.
Thoratec says the first 294 patients in the trial will be followed for six months to evaluate its utility in bridge-to-transplantation. The first 366 patients will be followed for 24 months to assess it for permanent use.
In Europe Thoratec has completed enrolment into HeartMate III’s CE mark study and expects approval and launch in late 2015.
HeartWare has a follow-up device too, MVAD, but this is some way behind Thoratec’s with enrolment into a first human trial, designed to permit CE marking, due to start this quarter.
The first feedback on the MVAD pump will be more important for the company than data from either of the Endurance cohorts, say analysts from Bank of America Merrill Lynch. This is expected late in the third quarter or early in the fourth, and if it is positive the pump's small size – it is a third the size of HVAD – could propel HeartWare to greater market share.
This could grow from around 44% today, compared with Thoratec’s 55%, to around 60% by 2020, they write. But this is contingent on HVAD gaining approval as destination therapy in 2017. And that will be more likely if stroke rates in the second cohort are lower than in the first.
To contact the writer of this story email Elizabeth Cairns in London at firstname.lastname@example.org or follow @LizEPVantage on Twitter