While Cytokinetics’ heart drug technically met its primary endpoint back in November, it missed a key secondary endpoint — reduction in cardiovascular death — which eventually cost the company two partnerships. Now the team is back with data suggesting the drug works better in sicker patients, and it’s planning a trip to the FDA.
In a post-hoc analysis, which can be a very difficult sale at the FDA, Cytokinetics separated patients from the Phase III GALACTIC-HF study into four quartiles based on ejection fraction, a measurement of how well the left ventricle pumps blood with each heartbeat. Patients in the lower two quartiles — those with an EF of 22% or lower, and between 29% to 32% — saw a 15% and 17% relative risk reduction of heart failure events and cardiovascular death combined, Cytokinetics reported at ACC. No difference was seen in the upper two quartiles.
The beneficial effect was mainly driven by a reduction in heart failure events, Cytokinetics said. When considering heart failure events alone, the relative risk reduction for the lower two quartiles was 19% and 17% respectively, with no difference seen in the upper two quartiles.
Fady Malik
“We enrolled in GALACTIC a patient population that had poor cardiac function but, you know, you don’t know ahead of time, ‘Well where should we draw that line,’” executive VP of R&D Fady Malik told Endpoints News. “If we had, say, gone with an EF of 30% or less versus 35% or less, the results would have looked substantially different.”
Omecamtiv mecarbil works by targeting myosin, a protein that converts chemical energy into mechanical force in the heart. In October, Cytokinetics announced the drug reduced the odds of hospitalization or other urgent care for heart failure by 8%, a statistically significant result.
However, even the subgroups with lower EF missed the secondary endpoint of a reduction in cardiovascular death, which analysts have been looking to as a key measure of success.
“In my view, without CV death benefit, the drug probably won’t be a foundational medicine and do the $4Bn in WW end-user sales that we had originally thought (consensus is ~$3.5Bn). But is it a zero? Maybe not,” Mizuho’s Salim Syed wrote after Cytokinetics unveiled its topline results back in October.
“I think it’s premature for analysts, or others, to jump to conclusions,” CEO Robert Blum told Endpoints on Friday.
Robert Blum
“While this is not perhaps foundational to the standard of care for every heart failure patient as might have been our aspiration … we foresee at Cytokinetics that this is a very important unmet need for which omecamtiv mecarbil and GALACTIC factors very importantly into what may be a solution for these patients,” he added.
Cytokinetics says it’s planning on submitting an NDA for the candidate in the second half of this year. Whether or not they’ll pursue an approval specifically for patients with lower EF is “something to be determined in concert with ongoing discussions with FDA,” Blum said.
In just a few days, Cytokinetics will officially lose its longtime partner Amgen, which shrugged off its 14-year alliance and the tens of millions of dollars it spent to develop omecamtiv back in November. Upon announcing the split, Amgen said the GALACTIC data “did not meet the high bar we had set for the program.” A month later, Les Laboratoires Servier and Institut de Recherches Internationales Servier said it was also pulling out of a sublicense agreement for omecamtiv that it struck with Amgen back in 2016.
At the time, Blum insisted on looking at the bright side, announcing he was “pleased to proceed into 2021 with clarity.”
When asked about the possibility of future collaborations, Blum said the company is in talks with “quite a number of companies” to commercialize omecamtiv outside the US. Cytokinetics plans on marketing the drug on its own within the US, both Blum and Malik said.
“You’ve got here a group of patients — not a small group at all, on the order of one to two million patients probably in the United States — who are severely ill, and are maxed out on standard of care. And yet with these analyses, we see they represent a population that needs a new therapy,” Blum said.
