Primary omecamtiv win is not enough

Normally meeting a clinical trial’s primary efficacy endpoint is considered a win. Not so for the Amgen/Cytokinetics heart failure project omecamtiv mecarbil, which investors virtually wrote off yesterday after seeing long-awaited results of the Galactic-HF trial.

This is because the pivotal study’s most important endpoint, in terms of real-world relevance, was cardiovascular death, a secondary outcome measure – and this was missed. Cytokinetics lost 42% yesterday, and with the disappointment laying bare Amgen’s poor pipeline the big biotech’s stock came off 7%.

Not only was the key secondary endpoint missed, but Galactic-HF’s primary measure, a composite of death or heart failure events, showed an underwhelming result: the 8% risk reduction versus standard of care (p=0.0252) seriously underperformed the 26% that Astrazeneca’s Farxiga has scored.

With Farxiga also having shown a pure mortality benefit, to the tune of a 17% risk reduction, this suggests that omecamtiv has no commercial future.

If this is the case Amgen needs to take a hard look at its pipeline. Apart from omecamtiv and biosimilars, its only other significant developmental assets are the Kras inhibitor sotorasib, and tezepelumab, an anti-TSLP MAb for respiratory indications.

On Monday Amgen issued a peculiar statement, saying sotorasib’s phase II effect in NSCLC was “consistent with previously reported phase I data”, but not revealing any results. This hinted at an early regulatory filing, and perhaps Amgen was trying to distract attention from the upcoming omecamtiv bombshell; in any case the Kras bubble is fast deflating.

The Astrazeneca-partnered tezepelumab, meanwhile, faces a key binary outcome event of its own, with results from the phase III Navigator study in severe non-eosinophilic asthma due this year. Excluding biosimilars tezepelumab is Amgen’s biggest pipeline hope in terms of forecast sales, but there are reasons for caution here, too.

What now for omecamtiv? Amgen and Cytokinetics said full data from Galactic-HF would be presented at a late-breaker during the American Heart Association meeting on November 13. They said nothing about filing plans, commenting only that the result provided insights into targeting cardiac muscle contractility with omecamtiv.

The asset is a cardiac myosin activator, binding to and aiming to recruit cardiac myosin heads to interact with actin during systole. It has a long history, having been in clinical development for many years; the Amgen/Cytokinetics tie-up dates back to January 2007, at which time the then phase I asset changed hands for $42m up front plus $33m of Cytokinetics equity.

Subgroups?

Leerink analysts speculated that one possibility now would be to look for a subgroup benefit in Galactic-HF, but as a means of getting omecamtiv approved this is unlikely to work unless demonstrated prospectively in a new study. Such a course of action seems unlikely, as does pursuing a further indication of heart failure with preserved ejection fraction.

It cannot be denied that for a study as overpowered as Galactic-HF, which recruited over 8,000 subjects, to yield such a mediocre result is disappointing. This will be great news for biotech followers, who will point to Amgen’s desperate need to fill its pipeline as a sign that it will have to buy projects in.

True, biotech assets for acquisition or licensing are extremely expensive at present, but Amgen ran out of alternatives some time ago.