Cytokinetics Regains European Rights to Omecamtiv Mecarbil

Rhea-AI Summary

Cytokinetics announced the termination of the sublicense agreement for omecamtiv mecarbil with Amgen and Servier, effective March 18, 2021. All rights revert to Cytokinetics after this date. The investigational drug, designed for treating heart failure, recently showed positive results in the GALACTIC-HF Phase 3 trial, demonstrating a statistically significant reduction in cardiovascular events. The company plans regulatory interactions in 2021 to discuss these results and evaluate strategic options for co-commercialization and licensing.

Positive

• Positive results from GALACTIC-HF trial showed a 8.1% absolute risk reduction in patients with lower ejection fractions.
• Cytokinetics plans to engage regulatory authorities in 2021 to discuss potential approval paths for omecamtiv mecarbil.

Negative

• Termination of the sublicense agreement could indicate uncertainty in partnerships.
• No reduction observed in time to cardiovascular death, with no secondary endpoints met.

Company is Planning Regulatory Interactions in 2021 to Discuss Results of GALACTIC-HF and Expects to Evaluate Strategic Options for Co-Commercialization and Licensing

SOUTH SAN FRANCISCO, Calif., Dec. 23, 2020 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) announced that Amgen Inc. (“Amgen”) notified the company that Les Laboratoires Servier and Institut de Recherches Internationales Servier (“Servier”) elected to terminate the sublicense agreement between Amgen and Servier (the “Servier Agreement”) for the development and commercialization of omecamtiv mecarbil in Europe and the Commonwealth of Independent States, including Russia. The termination is effective as of March 18, 2021, after which all development, commercialization and other rights with respect to omecamtiv mecarbil previously granted by Amgen to Servier will revert to Amgen. Cytokinetics recently announced that Amgen terminated the Collaboration and Option Agreement between Amgen and Cytokinetics effective May 20, 2021. Given Servier’s notice to Amgen, all worldwide rights related to the development and commercialization of omecamtiv mecarbil will now return to Cytokinetics on that date.

Omecamtiv mecarbil, an investigational cardiac myosin activator, developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF), was recently studied in GALACTIC-HF, a positive Phase 3 cardiovascular outcomes clinical trial. Cytokinetics announced that it intends to seek feedback from regulatory authorities in 2021 as may inform potential regulatory strategies. The company also expects to evaluate strategic options for the potential co-commercialization and licensing of omecamtiv mecarbil.

“We are pleased to proceed into 2021 with clarity regarding omecamtiv mecarbil. We look forward to engaging regulatory authorities next year with the objective to assess potential regulatory paths while also continuing our commercial planning activities.” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “Primary efficacy results as well as supplemental analyses from GALACTIC-HF point to potentially clinically relevant effects of omecamtiv mecarbil in patients with heart failure. We plan to evaluate a wide range of corporate development strategies for both co-commercialization and licensing deals to inform our goal to bring our novel mechanism drug candidate to patients suffering from heart failure.”

GALACTIC-HF: Primary Results and Supplemental Analyses

Primary results from GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 event-driven cardiovascular outcomes clinical trial of omecamtiv mecarbil, were recently presented at the American Heart Association (AHA) Scientific Sessions 2020, and were simultaneously published in the New England Journal of Medicine.¹

GALACTIC-HF, one of the largest Phase 3 global cardiovascular outcomes trials in heart failure ever conducted, enrolled 8,256 patients who were at risk of hospitalization and death, despite being well treated on standard of care therapy. After a median duration of follow-up of 21.8 months, the trial demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care. A first primary endpoint event occurred in 1,523 of 4,120 patients (37.0%) in the omecamtiv mecarbil group and in 1,607 of 4,112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI] 0.86, 0.99; p=0.025). This effect was observed without evidence of an increase in the overall rates of myocardial ischemic events, ventricular arrhythmias or death from cardiovascular or all causes. No reduction in the secondary endpoint of time to CV death was observed and no other secondary endpoints were met in accordance with the prespecified statistical analysis. The effect of omecamtiv mecarbil was consistent across most prespecified subgroups and with a potentially greater treatment effect suggested in patients with a lower left ventricular ejection fraction (LVEF ≤28%, n=>4,000, hazard ratio, 0.84; 95% CI 0.77, 0.92; interaction p=0.003). A supplemental analysis of the continuous relationship between ejection fraction and the hazard ratio for the primary composite endpoint in GALACTIC-HF suggests a potentially stronger treatment effect of omecamtiv mecarbil in patients with increasingly lower ejection fractions.

Additional analyses of this lower ejection fraction subgroup in GALACTIC-HF showed that a potentially greater treatment effect in patients who received omecamtiv mecarbil was consistently observed in patients with characteristics that may indicate advanced heart failure status, such as being hospitalized within the last 3 months (HR 0.83, 95% CI 0.74 – 0.93, p=0.001), having New York Association Class III or IV heart failure (HR 0.80, 95% CI 0.71 – 0.90, p<0.001), higher N-terminal-pro brain natriuretic peptide levels (HR 0.77, 95% CI 0.69 – 0.87, p<0.001), and lower blood pressures (HR 0.81, 95% CI 0.70 – 0.92, p=0.002). Absolute risk reductions ranged from 5.2% to 8.1% in these subgroups vs. 2.1% in the overall population.

About Omecamtiv Mecarbil and the Phase 3 Clinical Trials Program

Omecamtiv mecarbil is an investigational selective cardiac myosin activator, the first of a novel class of myotropes² designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Preclinical research showed omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.^3-5 Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell responsible for converting chemical energy into the mechanical force resulting in cardiac contraction.

Omecamtiv mecarbil is being developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF). Omecamtiv mecarbil is the subject of a comprehensive Phase 3 clinical trials program composed of GALACTIC-HF and METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity.

About Cytokinetics

Cytokinetics is a late-stage 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 muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact muscle function and contractility. Cytokinetics is preparing for regulatory interactions for omecamtiv mecarbil, its novel cardiac muscle activator, following positive results from GALACTIC-HF, a large, international Phase 3 clinical trial in patients with heart failure. Cytokinetics is conducting METEORIC-HF, a second Phase 3 clinical trial of omecamtiv mecarbil. Cytokinetics is also developing CK-274, a next- generation cardiac myosin inhibitor, for the potential treatment of hypertrophic cardiomyopathies (HCM). Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of CK-274 in patients with obstructive HCM. Cytokinetics is also developing reldesemtiv, a fast skeletal muscle troponin activator for the potential treatment of ALS and other neuromuscular indications following conduct of FORTITUDE-ALS and other Phase 2 clinical trials. The company is considering potential advancement of reldesemtiv to Phase 3 pending ongoing regulatory interactions. Cytokinetics continues its over 20-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness.

For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on Twitter, 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 relating to the GALACTIC-HF clinical trial; statements relating to the METEORIC-HF clinical trial; Cytokinetics’ activities to advance the development of omecamtiv mecarbil; the potential benefits of omecamtiv mecarbil, including its ability to represent a novel therapeutic strategy to increase cardiac muscle function and restore cardiac performance; the potential approval of omecamtiv mecarbil by the FDA or any other regulatory authority; the ability of Cytokinetics to secure a co-commercialization partner for omecamtiv mecarbil or to otherwise out-license omecamtiv mecarbil to a third party; Amgen’s fulfillment of its undertakings regarding transition of the omecamtiv mecarbil and AMG 594 programs to Cytokinetics; Cytokinetics' and its partners' research and development activities; the design, timing, results, significance and utility of preclinical and clinical results; and the properties and potential benefits of Cytokinetics' other drug candidates. 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, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics' drug candidates that could slow or prevent clinical development or product approval; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' or its partners' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; the nature of Amgen's decisions and activities with respect to the transfer of rights to develop and commercialize omecamtiv mecarbil and AMG 594 to Cytokinetics; standards of care may change, rendering Cytokinetics' drug candidates obsolete; competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target; and risks and uncertainties relating to the timing and receipt of payments from its partners, including milestones and royalties on future potential product sales under Cytokinetics' collaboration agreements with such partners. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission.

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

References

1. Teerlink J et al. NEJM. 2020
   
   
2. Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.
   
   
3. Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
   
   
4. Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010; 3: 522-27.
   
   
5. Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.

FAQ

What are the implications of Cytokinetics' recent sublicense termination for omecamtiv mecarbil?

The termination allows Cytokinetics to regain full rights to omecamtiv mecarbil, potentially centralizing its development and commercialization strategy.

What were the results of the GALACTIC-HF trial for omecamtiv mecarbil?

The GALACTIC-HF trial demonstrated a significant reduction in cardiovascular events, showing an absolute risk reduction of 8.1% in patients with lower ejection fractions.

What is Cytokinetics' plan for regulatory interactions in 2021?

Cytokinetics intends to seek feedback from regulatory authorities to inform potential regulatory strategies for omecamtiv mecarbil.

How will the termination of the agreement affect Cytokinetics' stock (CYTK)?

The full control over omecamtiv mecarbil could be seen as a strategic advantage, potentially boosting investor confidence in the company's future prospects.