ACC – Vericel in limbo as heart failure data sour
After Vericel's 80% share price hike two weeks ago, when its heart failure stem cell therapy hit its primary endpoint in phase II, the company has been brought back to earth by further data from the same study.
Ixmyelocel-T’s miss across the board on the ixCELL-DCM study’s secondary endpoints pushed the shares down 38% to $3.72 yesterday as investors realised that the therapy might not be as good as it looked at first glance. Potential partners for ixmyelocel-T could be hesitant too, meaning that for now Vericel looks unable to move its cell therapy into phase III.
The current situation with ixmyelocel-T is not a repeat of its crash in critical limb ischaemia three years ago, but it is certainly a letdown after the initially impressive showing in ixCELL-DCM (Pivotal data overshadows Vericel’s heart failure win, March 11, 2016).
The autologous stem cell therapy beat placebo on survival and cardiovascular hospitalisations and interventions in patients with advanced heart failure caused by ischaemic dilated cardiomyopathy. That achievement still stands – but the good news stops there.
The full 12-month data, presented yesterday at the American College of Cardiology meeting in Chicago, showed that on the study’s secondary endpoint known as the win ratio, ixmyelocel-T numerically beat placebo on time to death, left ventricular assist device placement, heart transplantation or time to cardiovascular hospitalisation, but the difference was not significant.
In this analysis, each of the 51 ixmyelocel-T-treated patients were compared with each of the 58 placebo-treated patients, giving 2,958 patient-pairs. In each pair the researchers looked at which patient died, received an LVAD, or got a heart transplant, first, assigning them the loser.
After that they worked sequentially through all the other endpoints, again labelling patients winners or losers. This resulted in a 1.56 win ratio for ixmyelocel-T wins over placebo wins, with a p value of 0.14.
Other secondary endpoints showed no advantage for Vericel’s project either. There were no significant structural changes in left ventricle cavity size or left ventricular ejection fraction as measured by echocardiogram in either the ixmyelocel-T or placebo groups. Both groups saw improvements in NYHA class and on the six-minute walk test, but again statistically there was nothing to choose between the two.
So what now? Vericel’s best bet to push into phase III is to partner ixmyelocel-T in Japan, say analysts at Ladenberg Thalmann. Writing in mid-March, they suggested that recent legislation in Japan permitting accelerated approval for cell therapy products meant that the country offered the quickest path to market; partnering ixmyelocel-T here would net Vericel the cash to fund global pivotal trials beginning in 2017.
Whether this new tranche of data puts paid to this strategy is not certain – there is some hope for Vericel in that the losses of yesterday have certainly not wiped out the gains made a month ago. But it might give potential partners pause, at least until pivotal data on Celyad’s heart failure stem cell technology C-Cure emerge in the next few months.
If Celyad can show a more emphatic victory than Vericel’s it could end up scoring a partner at Vericel’s expense. But shareholders do not seem to think this the likeliest outcome: Celyad is off 5% so far today, perhaps owing to fear of read-through from the Vericel data.
Vericel is not done for yet. But now it will have to work harder to find a partner and get phase III off the ground. If C-Cure is a washout in phase III Vericel’s situation could improve – at least it has a partial win, after all.