Cytokinetics’ cardiovascular pipeline beats strong

cytokinetics 1

Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which cardiac muscle performance is compromised.

This week, we have a conversation with the CEO of Cytokinetics, Robert Blum, about the company’s heart drug pipeline, including aficamten, its next-in-class cardiac myosin inhibitor, which has seen great results from a pivotal phase 3 clinical trial in obstructive hypertrophic cardiomyopathy. 

Table of contents

    The origin of Cytokinetics

    Blum explained that the company was set up in 1988 to mine a new area of biology for potential new medicines. 

    That area of biology is the cytoskeleton, and it has implication to the mechanical activities of cell behavior. Cytokinetics has been engaged in the discovery and development of potential new medicines that are modulators of proteins. Specifically, Blum said, this is focused on the mechanics of muscle contractility. New medicines are in late-stage development that address cardiovascular conditions associated with either hyper or hypo contractility of cardiac muscle for diseases of severe cardiovascular weakness. 

    Current treatments for cardiovascular diseases

    Blum said that while there are many new advances in cardiovascular medicine over recent decades, very few of those innovations relate to cardiac muscle directly. 

    “Most of the drugs act secondarily on the heart and more address consequences and symptoms associated with cardiovascular disease etiology. Cytokinetics’ medicines, as we are developing them, are designed specifically to modulate the proteins involved in the bio-machinery of cardiac muscle, and that would represent a major new advancement for innovation in cardiac disease,” Blum explained.

    “We’ve made good progress in cardiovascular diseases by addressing hypertension, high blood pressure, by addressing the formation of blood clots that can be complicating to cardiovascular patients by addressing things like cholesterol that can give rise to risk factors associated with cardiac illness. But unfortunately, those have come without accompanying innovations in medicines associated with cardiac muscle itself. 

    “And that’s where, hopefully, Cytokinetics can make a meaningful impact.” 

    Cardiovascular diseases in some figures

    According to the World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year. This represents 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke.

    More than three quarters of CVD deaths take place in low- and middle-income countries.

    Out of the 17 million premature deaths (under the age of 70) due to noncommunicable diseases in 2019, 38% were caused by CVDs, the WHO said.

    It’s also the number one reason why people are hospitalized, Blum added. 

    “Heart failure is the number one reason why patients are hospitalized and those patients are often hospitalized, discharged, readmitted again, again, and again. And that makes heart failure the leading cause of not only hospitalization, but also it is associated with the leading economic burden societally for those patients. 

    “So, it represents a major opportunity where new cardiovascular medicines could be welcomed, not just simply for the benefit of clinical evidence to support better quality of life and functional life, but also for the costs associated with healthcare. It’s a major opportunity for economic savings.” 

    About Cytokinetics heart drug pipeline


    Aficamten is a small molecule, a synthetic organic compound discovered by Cytokinetics. It binds directly to cardiac myosin. 

    Cytokinetics has reported positive results from SEQUOIA-HCM, its pivotal phase 3 clinical trial in obstructive hypertrophic cardiomyopathy. 

    “Our R&D strategies, our corporate and business development strategies, have enabled us to build a very valuable company, valuable to patients as well as shareholders.”

    Cytokinetics CEO, Robert Blum

    Cytokinetics’ heart drug Aficamten is also currently being evaluated in MAPLE-HCM, a phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM. Other trials include ACACIA-HCM, a phase 3 clinical trial of aficamten in patients with non-obstructive HCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM; and FOREST-HCM, an open label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (HCM).

    “We expect many more presentations and publications from the ongoing clinical trials of aficamten this year,” Blum said.

    The company also recently announced the start of another clinical trial for aficamten in pediatric patients with obstructive hypertrophic cardiomyopathy. 

    As it is a synthetic organic compound, it can be administered orally once a day, Blum said.

    The company is now engaging now with regulatory authorities in the US and Europe, with the goal being aficamten would be available to patients in 2025.

    Patients who currently have hypertrophic cardiomyopathy have few treatment options, and they live with a heavy symptom burden, Blum said.

    However, in the clinical trial, aficamten was associated with a clinically meaningful improvement in exercise capacity and stamina, as well as improvements in measures of quality and functional life.


    Blum also revealed that Cytokinetics has advanced CK-586, a compound similar to aficamten, but with a distinct mechanism of action, is advancing from phase 1 to phase 2. 

    “CK-586, like aficamten, is a cardiac myosin inhibitor. It’s being studied in an adjacent indication to hypertrophic cardiomyopathy, and that indication is called heart failure with preserved ejection fraction.”

    Blum noted that heart failure represents a much larger prevalent population in the US, with more than 5 million patients with heart failure in comparison to a few hundred thousand with hypertrophic cardiomyopathy. 

    “We’re looking at heart failure with preserved ejection fraction, which represents about half of that prevalent population of heart failure, and a subset of those patients have hypercontractility that resembles in profile similar to non-obstructive hypertrophic cardiomyopathy. 

    “We’re going to be advancing into phase 2 later this year, CK-586 as a potential treatment for those patients with heart failure and preserved ejection fraction who, similar to patients with non-obstructive hypertrophic cardiomyopathy, have high ejection fractions, hypercontractility, and where they too could benefit from symptom relief and addressing of their underlying cardiac myosin disorder. 

    “With this announcement, we’re further expanding our pipeline and reach of this biology, this innovative new pharmacology, to a new patient population.” 


    Another drug in Cytokinetics’ pipeline is CK-136, a cardiac troponin activator for the potential treatment of heart failure with reduced ejection fraction and other types of heart failure, such as right ventricular failure resulting from impaired cardiac contractility.

    Cytokinetics’ heart drug CK-136 is in phase 1 evaluation for potential progression to phase 2. 

    Omecamtiv mecarbil

    Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator drug, in patients with heart failure.

    “Think of it as the flip side of the cardiac myosin inhibitor,” Blum explained.

    “We studied it in over 30 clinical trials to assess its potential to treat heart failure with reduced ejection fraction. It was the subject of a positive phase 3 study called GALACTIC, and that study was the subject of a regulatory application for potential approval, but for which the FDA indicated that while positive, they would like to see a confirmatory study. 

    “So, we are still in the process of assessing what would be potential next steps.”

    Cytokinetics acquisition rumors

    In 2023, there were rumors of a potential takeover of Cytokinetics by more than one large biopharma companies.

    However, those acquisition stories faded, and now Cytokinetics is looking to extend its business model to take advantage of its heart drug pipeline.

    “We’ve got several advancing programs in development that would be all directed to the same concentrated customer segment, enabling a rapidity of potential product approvals and potential medicines directed to the same opportunities in a way that would enable a high return on R&D investment, a high return on sales and marketing investment, and therefore a high return on shareholder equity,” Blum said. 

    “And we believe this is the path to building a sustainable, enduring company, as could be rewarding to shareholders, and at the same time deliver on the promise of our science for potential benefit to more and more cardiovascular patients. As we’re embarking on this strategy, we believe that we’re in an advantage position to go to market ourselves in North America and also Europe.

    “We also recognize limitations and we will seek partners in certain geographies. We’re diversifying our access to capital to ensure that we deploy capital in the most efficient way. And I think our R&D strategies, our corporate and business development strategies, have enabled us to build a very valuable company, valuable to patients as well as shareholders.”

    To learn more about this topic

    Here are some links to more articles on the subject of treating heart conditions.

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