Cytokinetics (CYTK), is a late clinical-stage biopharmaceutical company focusing on the development and commercialization of muscle activators and inhibitors as therapeutics for cardiovascular disorders. These small molecules are believed to optimize muscle function and contractility. The main asset, Omecamtiv mecarbil is a cardiac myosin activator that is investigated as a treatment for heart failure and is waiting for the USFDA marketing application approval. The USFDA has raised safety concerns and observed limited efficacy, and the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 8-3 against the marketing approval. The panel observed the drug’s potential benefits did not outweigh the risks. The marketing approval application for Omecamtiv mecarbil is under regulatory agency review with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2023.
The next important pipeline Reldesemtiv is being investigated in Phase III clinical trial as a treatment for amyotrophic lateral sclerosis (ALS). It is noteworthy to mention – the drug terribly failed to meet all the endpoints in Phase II clinical trial (no better than the sham treatment group), and still pushed forward to the Phase III study.
Another important pipeline Aficamten, a novel cardiac myosin inhibitor is in Phase III study as a treatment for symptomatic obstructive hypertrophic cardiomyopathy. The safety and efficacy of Aficamten, particularly in long-term studies is yet to be demonstrated beyond doubt.
Recent Events
December 14th, 2022 – FDA Adcomm gave thumbs down to Cytokinetics’ heart failure candidate
December 9th, 2022 – Cytokinetics announced the availability of briefing documents for the FDA Advisory Committee Meeting on Omecamtiv Mecarbil
December 7th, 2022 – Cytokinetics announced the initiation of Phase 1 clinical study of CK-3828136
Addressable market
The HCM market size was around USD 301.3 million in 2020 and is estimated to reach USD 1.9 billion by 2029.
The prevalence of HCM among the adult population is estimated to be 0.16% to 0.29% ((≈ 1:625–1:344)
Current finances:
Cytokinetics has a considerable amount of cash on hand, with an estimated $896 million available to fund operations for the next two years. The company’s projected R&D spending for 2023 is approximately $148 million, with a significant portion of that budget allocated towards the development of Aficamten. Specifically, it is estimated that spending for Aficamten accounts for approximately 60% of the total R&D budget for the year. This highlights the importance of Aficamten in the company’s pipeline, and the significant resources being dedicated towards its advancement. It is worth noting that having a sufficient cash reserve is crucial for a biopharmaceutical company like Cytokinetics as it allows them to continue to invest in research and development, as well as maintain operations. With this in mind, the company’s strong financial position is a positive sign for the future.
Insider activity
Competitors:
Bristol-Myers Squibb is developing Mavacamten (MYK-461) for the management of symptomatic obstructive hypertrophic cardiomyopathy and the study is in a phase II clinical trial.
Celltrion is conducting a phase I clinical trial to assess the pharmacokinetics and pharmacodynamics of CT-G20 as a treatment for obstructive hypertrophic cardiomyopathy.
Summary
As a result of the negative vote by the US FDA panel, it is highly unlikely that the regulatory agency will approve the marketing application for Omecamtiv mecarbil. Should this be the case, CYTK can redirect its capital towards other segments of its pipeline. Additionally, there is always the possibility of addressing/revisiting the FDA’s findings in the future. The main short term concern is the potential impact on the company’s share price, and hence its ability to raise further cash at a decent valuation. However, for investors who are willing to take a long-term view, there may be value to be found in this company.
In the long term, there’s Aficamten (an investigational, novel, oral, small molecule cardiac myosin inhibitor), a different asset in CYTK‘s pipeline, might turn into its lead compound. However, it is important to note that the science, efficacy and safety of Aficamten have yet to be proven. Investing in CYTK carries a significant level of risk at these levels – with the PDUFA date just weeks away.