Cytokinetics Stock: Emerging Leader In Heart Failure Drugs

Cytokinetics (NASDAQ:CYTK) is a developer of small molecule drugs for cardiovascular and neuromuscular diseases of impaired muscle function. The lead drug candidate is Omecamtiv mecarbil, a novel, selective cardiac myosin activator for the treatment of heart failure with reduced ejection fraction (HFrEF), which has produced mixed data in heart failure patients in a pivotal phase 3 trial.

Omecamtiv was partnered with Amgen since 2007, but they walked away in 2020 after the GALACTIC-HF trial performed poorly on cardiovascular death, a key secondary endpoint. Not only that, it also underperformed on the primary endpoint, where its 8% risk reduction in the composite measure of death or heart failure (p=0.0252) was much less than AstraZeneca’s Farxiga’s 26%. Omecamtiv has a PDUFA on November 30 (now extended to Feb 28, 2023 to review additional pharmacokinetic data), but the FDA has asked for a surprise advisory committee meeting or adcom. Given that Farxiga, the drug already approved in heart failure, also scored 17% in the CV death endpoint, Omecamtiv’s future in the market is in doubt.

However, in a subgroup of patients with severe heart failure – comprising patients with NYHA level III-IV and ejection fraction at or below 30% – Omecamtiv showed a much better CV death reduction profile, at 20%. The fact that GALACTIC-HF’s data was driven by positive data from this subgroup, and that in patients with less severe disease Omecamtiv had almost zero effect, bolsters the subgroup angle. This is the subgroup which will be the target of the PDUFA, however, what needs to be seen is whether the FDA will approve based on post hoc subgroup analysis alone, or ask for a new trial.

The company was seeking a potential label expansion for Omecamtiv with the Meteoric-HF trial assessing Omecamtiv’s efficacy in improving exercise capacity in heart failure patients. Although not directly relevant to the PDUFA, this could have added a label expansion and bolstered the general case for Omecamtiv. However, Meteoric-HF was a failure, showing Omecamtiv to be no better than placebo in improving exercise capacity in reduced ejection fraction patients. This has further reduced investor expectations surrounding Omecamtiv.

The other heart muscle candidate is aficamten, not a myosin activator but an inhibitor, which has completed a positive phase 2 trial in the rare disease hypertrophic cardiomyopathy (HCM), and is currently enrolling patients in a pivotal phase 3 trial in obstructive HCM.

Analysts seem to be more upbeat about aficamten, however, with estimates of blockbuster status by 2028. Interestingly, MyoKardia, a spinoff of Cytokinetics, was acquired by Bristol-Myers Squibb (BMY) for $13bn, and BMY, through this acquisition, now has an approved drug called in this Camzyos (mavacamten) very indication. Camzyos was approved in April, giving it at least 18 months’ lead over aficamten, however, it has seen some patients whose LVEF (left ventricular ejection fraction) dropping too low, needing dose adjustments and interruptions. Cytokinetics thinks aficamten can avoid these. Moreover, the company thinks that, if approved, its marketing efforts will be helped by BMY’s own pioneering educational efforts, and also by the high price of Camzyos, at $90,000 per year. Also, while there are 100,000 estimated patients of HCM in the US, that number could be an underestimation.

The company also announced positive data from this asset in the Redwood-HCM trial. The drug did significantly better than both placebo (as well as BMY’s mavacamten in a cross-trial analysis) in improving blood flow in these patients.

So the situation Cytokinetics finds itself in is this: this is a company with nearly two decades trying to become the leader in heart disease drug development. Its lead drug is an all-round failure, and even if it manages an approval based on a subgroup analysis, its market potential is vastly diminished. Its second drug has more potential, however, it still needs to show its merit in a phase 3 study. If the first drug fails, but the second drug succeeds, then they have a future. This seems to be the more likely outcome of its efforts.

Financials

CYTK has a market cap of $4.05bn and a cash balance of $686mn. Research and development expenses for the first quarter 2022 were $45.9 million, while general and administrative expenses were $33.1 million. At that rate, they have a cash runway of more than 8 quarters. The company made two small deals with Royalty Pharma (RPRX) for both their lead candidates, in order to fund the commercialisation of Omecamtiv. The total deal amount was $450mn.

Bottom Line

CYTK is a very interesting stock, and aficamten may one day attain blockbuster status. However, Omecamtiv is in a very doubtful position, and I am not sure of its chances of approval. CYTK stock is trading too high now. If Omecamtiv fails, it will fall, and I think it will actually de-risk the stock by making its valuation tied to aficamten alone. I will then consider buying CYTK.

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