Cytokinetics Presents Additional Data from SEQUOIA-HCM at the HCMS Scientific Sessions

Rhea-AI Summary

Cytokinetics (Nasdaq: CYTK) presented additional data from SEQUOIA-HCM, the Phase 3 trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), at the HCMS Scientific Sessions. The new analysis showed that aficamten treatment was associated with beneficial changes in five indices reflecting structural, electrophysiologic, and biomarker changes compared to placebo at 24 weeks:

• Improvement in maximal wall thickness (47.9% vs 30.7%; p=0.003)
• Improvement in left atrial volume index category (46.8% vs. 18.7%; p<0.001)
• Resolution of ECG changes consistent with left ventricular hypertrophy (19.0% vs. 4.3%; p<0.001)
• Normalization of hyperdynamic left ventricular ejection fraction (35.2% vs 20.7%; p<0.007)
• Reduction in NT-proBNP by ≥50% from baseline (81.7% vs. 7.1%; p<0.001)

Overall, 83.8% of patients treated with aficamten experienced favorable effects in at least one of the five domains, compared to 39.3% of patients on placebo (p<0.001, NNT = 2.2).

Positive

• Aficamten showed significant improvements in multiple cardiac structural and functional indices compared to placebo
• 83.8% of patients treated with aficamten experienced favorable effects in at least one of the five domains vs 39.3% on placebo
• The Number Needed to Treat (NNT) was low at 2.2, indicating high treatment efficacy

Negative

• None.

Insights

Medical Research Analyst

This new analysis from the SEQUOIA-HCM trial provides compelling evidence of aficamten's potential in treating obstructive hypertrophic cardiomyopathy (HCM). The data shows significant improvements across multiple cardiac parameters compared to placebo:

• Reduction in maximal wall thickness (47.9% vs 30.7%, p=0.003)
• Improvement in left atrial volume index (46.8% vs 18.7%, p<0.001)
• Resolution of ECG changes (19.0% vs 4.3%, p<0.001)
• Normalization of left ventricular ejection fraction (35.2% vs 20.7%, p<0.007)
• Reduction in NT-proBNP (81.7% vs 7.1%, p<0.001)

The overall impact is substantial, with 83.8% of aficamten-treated patients showing improvement in at least one domain versus 39.3% for placebo (NNT = 2.2). These results suggest aficamten could potentially modify the disease course in HCM patients, addressing both structural and functional cardiac abnormalities. The ongoing FOREST-HCM extension study will be important in assessing long-term outcomes and safety.

Financial Analyst

The positive clinical data from SEQUOIA-HCM strengthens Cytokinetics' position in the HCM treatment market. With a market cap of $6.25 billion, CYTK's valuation heavily depends on aficamten's success. This data supports the drug's efficacy, potentially increasing its chances of FDA approval and market adoption.

Key financial implications include:

• Market potential: HCM affects about 1 in 500 people, representing a significant addressable market.
• Competitive advantage: Aficamten's multi-domain benefits could differentiate it from existing treatments.
• Revenue prospects: If approved, aficamten could become a blockbuster drug, significantly boosting CYTK's revenue.
• R&D validation: Success in HCM may increase confidence in Cytokinetics' broader cardiac drug pipeline.

Investors should monitor upcoming regulatory milestones and potential partnerships or licensing deals, which could further impact CYTK's valuation. The withdrawal of the poster presentation due to Hurricane Helene is a minor setback but unlikely to have a material impact on the overall positive momentum.

SOUTH SAN FRANCISCO, Calif., Sept. 27, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that additional data from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), were presented at the Hypertrophic Cardiomyopathy Medical Society (HCMS) Scientific Sessions by Anjali T. Owens, M.D., Medical Director of the Center for Inherited Cardiac Disease and Assistant Professor of Medicine at the University of Pennsylvania.

A new analysis from SEQUOIA-HCM showed that treatment with aficamten was associated with beneficial changes in five indices reflecting structural, electrophysiologic and biomarker changes in patients from SEQUOIA-HCM. This analysis was performed in patients treated with aficamten and compared to placebo, at 24 weeks as follows:

• Improvement in maximal wall thickness by ≥1.5 mm (n = 282; 47.9% vs 30.7%; p=0.003)
• Improvement in left atrial volume index (LAVI) category in those with mild, moderate, or severe enlargement at baseline (n = 185; 46.8% vs. 18.7%; p<0.001)
• Resolution of ECG changes consistent with left ventricular hypertrophy (n = 282; 19.0% vs. 4.3%; p<0.001)
• Normalization of hyperdynamic left ventricular ejection fraction (defined as ≥72%) into the normal range (n = 282; 35.2% vs 20.7%; p<0.007)
• Reduction in NT-proBNP by ≥50% from baseline (n = 282; 81.7% vs. 7.1%; p<0.001).
  

Overall, 83.8% of patients treated with aficamten experienced favorable effects in at least one of the five domains, compared to 39.3% of patients on placebo (p<0.001, NNT = 2.2).

“This new analysis evaluated clinical data from SEQUOIA-HCM through the lens of remodeling to characterize the impact of treatment with aficamten in patients with obstructive HCM in terms of structural and functional changes. The results demonstrated favorable remodeling across multiple domains, including cardiac structure and function, electrophysiology and biochemistry,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “We are encouraged by these findings, and we look forward to further expanding our understanding of the long-term clinical outcomes of treatment with aficamten through our continued conduct of FOREST-HCM, the open-label extension clinical study.”

Poster Abstract Presentation Update

Due to Hurricane Helene and its expected impact to the Atlanta, GA area, the HCMS Scientific Sessions have converted from in person to virtual presentations. As such, the Company has decided to withdraw the poster entitled “Efficacy and Safety of Aficamten in Patients with Obstructive Hypertrophic Cardiomyopathy and Very High Left Ventricular Outflow Tract Gradients” from the sessions. The Company plans to submit the poster for presentation at a future medical meeting where it can be presented in person.

About Aficamten

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.

The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten was evaluated in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.

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, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, and 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 HCM.

About Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.^1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.⁴ People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.⁵ A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.

About Cytokinetics

Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Cytokinetics is preparing for regulatory submissions for aficamten, its next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy which were published in the New England Journal of Medicine. 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, 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 HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF.

For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements express or implied relating to the properties or potential benefits of aficamten or any of our other drug candidates, our ability to obtain regulatory approval for aficamten for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad, and the labeling or post-marketing conditions that FDA or another regulatory body may require in connection with the approval of aficamten. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.

Contact:
Cytokinetics
Diane Weiser
Senior Vice President, Corporate Affairs
(415) 290-7757

References:

1. CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575
2. Symphony Health 2016-2021 Patient Claims Data DoF;
3. Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.
4. Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.
5. Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21
   
   

FAQ

What were the key findings from the SEQUOIA-HCM trial for Cytokinetics' aficamten (CYTK)?

The SEQUOIA-HCM trial showed that aficamten treatment was associated with beneficial changes in five indices reflecting structural, electrophysiologic, and biomarker changes in patients with obstructive HCM. These included improvements in maximal wall thickness, left atrial volume index, resolution of ECG changes, normalization of left ventricular ejection fraction, and reduction in NT-proBNP levels.

How many patients treated with aficamten experienced favorable effects in the SEQUOIA-HCM trial (CYTK)?

83.8% of patients treated with aficamten experienced favorable effects in at least one of the five domains studied, compared to 39.3% of patients on placebo. The Number Needed to Treat (NNT) was 2.2, indicating high treatment efficacy.

What was the impact of aficamten on NT-proBNP levels in the SEQUOIA-HCM trial (CYTK)?

In the SEQUOIA-HCM trial, 81.7% of patients treated with aficamten showed a reduction in NT-proBNP by ≥50% from baseline, compared to only 7.1% in the placebo group. This difference was statistically significant with a p-value <0.001.

When and where were the additional SEQUOIA-HCM trial results for aficamten (CYTK) presented?

The additional data from the SEQUOIA-HCM trial were presented at the Hypertrophic Cardiomyopathy Medical Society (HCMS) Scientific Sessions on September 27, 2024, by Dr. Anjali T. Owens from the University of Pennsylvania.