Sarcomere Drug Pipeline: HCM & HFrEF — PatSnap Eureka
Sarcomere-Targeting Drugs in HCM & HFrEF: Myosin and Troponin Modulation
Hypertrophic cardiomyopathy and heart failure with reduced ejection fraction share sarcomere dysfunction as a central driver. From mavacamten to emerging myosin RLC modulators, explore the full patent-mapped pipeline via PatSnap Eureka.
Sarcomere Drug Modalities by Development Stage
Myosin inhibitors lead with Phase 3 evidence; RNA and gene-based approaches remain preclinical.
Sarcomere Dysfunction Drives Both HCM and HFrEF
In HCM, the core pathophysiological frame is excessive myosin–actin cross-bridge formation resulting in hypercontractility, impaired left ventricular filling, and progressive diastolic dysfunction. Retrieved patent filings from MyoKardia, Inc. explicitly characterize HCM as "a chronic progressive disease in which excessive contraction of the myocardium and reduced left ventricular filling capacity can lead to debilitating symptoms," with a prevalence of approximately 1 in 500 individuals.
The most common etiological agents are mutations in sarcomeric proteins, including β-myosin heavy chain (MYH7), cardiac myosin binding protein C (MYBPC3), troponin T (TNNT2), troponin I (TNNI3), troponin C (TNNC1), myosin regulatory light chain (MYL2), and essential light chain (MYL3)—as enumerated in a retrieved Chinese genetic diagnostic patent covering up to 312 genes associated with inherited cardiomyopathy and arrhythmia.
For HFrEF, retrieved results from Amgen's filing on omecamtiv mecarbil situate the sarcomere—specifically cardiac myosin—as the cell-autonomous generator of contractile force. Current positive inotropes are criticized for elevating intracellular calcium as an indirect mechanism that increases arrhythmic risk, establishing the therapeutic rationale for direct sarcomere activation.
According to the World Health Organization, cardiovascular disease remains the leading cause of death globally, making mechanistically targeted cardiac therapies a critical unmet need. The PatSnap analytics platform enables IP teams to map this evolving sarcomere patent landscape in real time.
Six Mechanistic Approaches Targeting the Cardiac Sarcomere
From approved myosin inhibitors to preclinical RNA-based strategies, the sarcomere drug pipeline spans multiple structural and mechanistic classes.
Cardiac Myosin Inhibitors (Mavacamten & Aficamten)
MyoKardia, Inc. describes mavacamten as an "allosteric modulator of cardiac myosin" that reduces excess myosin–actin cross-bridge formation, lowering myocardial contractility. Multiple filings cover obstructive HCM, non-obstructive HCM, and HFpEF. A 2025 Cytokinetics patent describes aficamten (CK-274) with an echocardiogram-guided dose-titration protocol for nHCM and mid-ventricular obstructive HCM.
Phase 3 (EXPLORER-HCM, MAVERICK-HCM, PIONEER)Cardiac Myosin Activators (Omecamtiv Mecarbil)
Amgen discloses omecamtiv mecarbil as a "small-molecule cardiac myosin activator" that directly augments cardiac myosin ATPase activity and the proportion of myosin heads in the force-generating state, increasing systolic ejection time without raising intracellular calcium concentrations—contrasting favorably with conventional positive inotropes.
Phase 2/3 SignalMyosin RLC Modulators (Achivos Dihydroquinazolinone)
A 2025 Achivos Therapeutics (Aizhi Wise) filing explicitly claims "modulation of myosin regulatory light chain (e.g., cardiac myosin regulatory light chain)" as the mechanism for treating HCM, including patients with MYL2 mutations. This differentiates the compound from mavacamten, which targets the myosin head domain, suggesting a distinct allosteric binding site.
Preclinical · Structurally NovelAllele-Specific RNA Silencing (Harvard College)
Harvard College filed a patent describing allele-specific RNA silencing for HCM, DCM, and LVNC. This modality uses RNAi to specifically silence the dominant-negative mutant allele of sarcomere genes (e.g., MYH7, MYBPC3), preserving wild-type protein function—addressing the autosomal dominant nature of HCM mutations where haploinsufficiency of the mutant allele is the therapeutic goal.
PreclinicalKey Data Signals from the Sarcomere Patent Landscape
All data derived from patent and literature records retrieved via PatSnap Eureka across targeted searches in HCM and HFrEF sarcomere modulation.
Assignee Share of Retrieved Sarcomere Patent Filings
MyoKardia/BMS holds the highest density of HCM-specific sarcomere filings; University of Texas anchors foundational miRNA IP.
Sarcomere Gene Targets by Citation Frequency in HCM Patents
MYH7 and MYBPC3 are the most frequently cited sarcomere gene targets; MYL2 gains prominence via the 2025 Achivos filing.
Sarcomere Patent Filing Activity by Era (2009–2025)
Foundational miRNA IP (2009–2014) has matured; commercial myosin inhibitor filings accelerated 2022–2025 with new entrants emerging.
Mechanistic Differentiation: Myosin Inhibition vs. Activation
Mavacamten reduces cross-bridge formation in HCM; omecamtiv mecarbil increases force-generating myosin heads in HFrEF—opposite pharmacological poles for distinct indications.
Key Patent Assignees in the Sarcomere Drug Pipeline
Commercial IP is concentrated in a small number of biopharma companies with strong sarcomere-specific focus, spanning multiple jurisdictions.
| Assignee | Compound / Strategy | Target | Jurisdictions | Filing Period | Stage |
|---|---|---|---|---|---|
| MyoKardia / BMS | Mavacamten (MYK-461); THP-pyrimidinedione series | β-MHC allosteric inhibitor | CN, JP, SG, MX | 2022–2025 | Phase 3 |
| Cytokinetics, Inc. | Aficamten (CK-274/CK-3773274); Formula I sarcomere inhibitors | Cardiac myosin inhibitor | JP, IL | 2023–2025 | Phase 3 |
| Amgen Inc. | Omecamtiv mecarbil | Cardiac myosin activator | CN | 2023 | Phase 2/3 |
| Achivos Therapeutics | 1,4-dihydroquinazolinone compounds | Myosin RLC modulator | CN | 2025 | Preclinical |
| Univ. of Texas System | Anti-miR-208, anti-miR-499; dual miRNA targeting | miR-208/β-MHC axis | MX, JP, KR, HK | 2009–2012 | Preclinical (foundational IP) |
| MiRagen Therapeutics | Anti-miR-208a; serum miRNA biomarker | miR-208a / β-MHC | JP | 2014 | Preclinical |
Track Every New Sarcomere Filing Across All Jurisdictions
PatSnap Eureka monitors patent landscapes in real time — set alerts for new HCM and HFrEF filings from any assignee.
What the Sarcomere Patent Landscape Signals for Drug Developers
Key IP strategy and R&D positioning insights derived from retrieved patent and literature signals.
Myosin Inhibition Is the Most IP-Dense Modality
MyoKardia (Bristol Myers Squibb) holds a multi-jurisdictional portfolio spanning treatment methods, dosing protocols, risk management, and diagnostic companion methods for mavacamten. Compound-specific method claims, patient subgroup claims, and dosing protocol claims collectively create layered exclusivity extending well beyond composition-of-matter protection.
A Third Structural Class Entered the Patent Record in 2025
The Achivos Therapeutics dihydroquinazolinone series targeting cardiac myosin regulatory light chain may constitute freedom-to-operate space differentiated from the allosteric myosin head-targeting inhibitors. Drug developers should monitor claim scope of this filing relative to existing MyoKardia and Cytokinetics IP.
Combination Approaches and Adjacent Sarcomere Strategies
Retrieved patent signals identify several combination and strategic directions beyond first-generation myosin inhibitor monotherapy.
Myosin Inhibitor + Beta-Blocker Withdrawal
A 2023 MyoKardia CN patent explicitly addresses "treatment in the absence of beta-blocker therapy or with reduced beta-blocker therapy," suggesting that mavacamten is being investigated as a potential replacement for or reducer of background neurohumoral therapy in HCM patients—a clinically significant shift in management philosophy.
Mavacamten · CN Patent 2023Myosin Inhibitor + Standard HCM Background Therapy
The THP-substituted bicyclic pyrimidinedione patent from MyoKardia (2022, JP) lists combination use with ACE inhibitors, ARBs, beta-blockers, aldosterone receptor antagonists, neprilysin inhibitors, positive inotropes, diuretics, calcium channel blockers, and vascular smooth muscle myosin modulators as within scope—indicating clinical positioning in multiply-treated patients.
THP-Pyrimidinedione · JP Patent 2022PPARγ Agonist / MPC Inhibitor for HCM
A 2024 CN patent (Prophylaxis Therapeutics Ltd.) proposes PPARγ agonists (thiazolidinediones) and MPC inhibitors as treatments for primary, congenital HCM and DCM, including restrictive HCM. While not directly sarcomere-targeting, this signals interest in metabolic reprogramming as an adjunct or alternative to direct myosin modulation.
PPARγ / MPC · CN Patent 2024HDAC6 Inhibition for DCM (HFrEF)
Tenaya Therapeutics, Inc. filed a 2024 BR patent on HDAC6 inhibitors for treating DCM with reduced ejection fraction, including oral administration routes. This represents a chromatin and cytoskeletal remodeling approach that may intersect with sarcomere organization through desmin and tubulin networks.
HDAC6 Inhibitor · BR Patent 2024Sarcomere Drug Pipeline in HCM & HFrEF — key questions answered
Mavacamten is an allosteric modulator of cardiac myosin that reduces excess myosin–actin cross-bridge formation, lowering myocardial contractility. The mechanism addresses the root cause in genetically driven HCM rather than downstream neurohormonal consequences.
Omecamtiv mecarbil directly augments cardiac myosin ATPase activity and the proportion of myosin heads in the force-generating state, thereby increasing systolic ejection time without raising calcium concentrations. Conventional positive inotropes elevate cyclic AMP and intracellular calcium, increasing arrhythmic risk.
Aficamten (CK-274/CK-3773274) is a cardiac myosin inhibitor filed by Cytokinetics, Inc. in a 2025 patent specifically addressing treatment of non-obstructive HCM (nHCM) and mid-ventricular obstructive (MVO) HCM. The patent describes an echocardiogram-guided dose-titration protocol.
miR-208a (encoded in MYH6 intron) emerges as a master regulator of the α-MHC/β-MHC isoform switch during cardiac stress. Anti-miR-208a treatment in preclinical models reduces β-MHC (MYH7) expression, attenuates hypertrophy, and improves diastolic function parameters—providing a pharmacological logic for therapeutic miRNA inhibition in HCM.
The 2025 Achivos Therapeutics dihydroquinazolinone patent explicitly claims modulation of myosin regulatory light chain (e.g., cardiac myosin regulatory light chain) as the mechanism of action for treating HCM patients, including those with MYL2 mutations. This differentiates the compound from mavacamten (which targets the myosin head domain) and suggests a distinct allosteric binding site.
Troponin complex and MyBP-C remain underexploited as direct small-molecule therapeutic targets relative to myosin head-domain inhibitors. Retrieved data positions these primarily as biomarkers (MyBP-C for diastolic HF; troponins for myocardial damage) or as genetic substrates for RNAi. This gap represents a potential white space for direct troponin sensitizer or troponin mutation-correcting modalities.
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References
- Myosin modulator treatment methods — MyoKardia, Inc., 2023, Japan [Patent]
- Methods of treatment with myosin modulator — MYOKARDIA, INC., 2022, Singapore [Patent]
- Methods of treatment with myosin modulator (with mavacamten and clinical trial references) — MYOKARDIA, INC., 2022, Mexico [Patent]
- Methods of administering myosin inhibitor (risk mitigation and distribution control) — MyoKardia, Inc., 2025, China [Patent]
- Methods of treatment with myosin modulator using mavacamten (beta-blocker context) — MyoKardia, Inc., 2023, China [Patent]
- Treatment methods using myosin modulators (diagnostic and therapeutic, CN) — MyoKardia, Inc., 2022, China [Patent]
- Cardiac sarcomere inhibitors — CYTOKINETICS, INC., 2023, Israel [Patent]
- Method for treating non-obstructive hypertrophic cardiomyopathy — Cytokinetics, Inc., 2025, Japan [Patent]
- Methods of treating heart failure by administering omecamtiv mecarbil — Amgen Inc., 2023, China [Patent]
- Tetrahydropyran (THP)-substituted bicyclic pyrimidinedione compounds — MyoKardia, Inc., 2022, Japan [Patent]
- 1,4-dihydroquinazolinone compounds and uses thereof — Achivos Therapeutics Co., Ltd., 2025, China [Patent]
- Allele-specific RNA silencing for the treatment of hypertrophic cardiomyopathy — PRESIDENT AND FELLOWS OF HARVARD COLLEGE, 2015, Canada [Patent]
- Identification of a micro-RNA that activates expression of beta-myosin heavy chain — BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM, 2009, Mexico [Patent]
- Dual targeting of mir-208 and mir-499 in the treatment of cardiac disorders — Board of Regents, The University of Texas System, 2012, Japan [Patent]
- microRNAs that regulate myosin expression and muscle fiber identity — Board of Regents, The University of Texas System, 2010, Japan [Patent]
- Serum miRNA as a surrogate marker of drug efficacy for cardiac pathology — MiRagen Therapeutics, 2014, Japan [Patent]
- Application of heart-specific kinase for diagnosis and treatment of cardiac insufficiency — National Cerebral and Cardiovascular Center, 2009, Japan [Patent]
- HDAC6 inhibitors for use in the treatment of dilated cardiomyopathy — TENAYA THERAPEUTICS, INC., 2024, Brazil [Patent]
- World Health Organization — Cardiovascular Disease Global Data
- National Institutes of Health — HCM Research Resources
- American College of Cardiology — HCM and HFrEF Clinical Guidelines
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records retrieved across targeted searches and represents a snapshot of innovation signals within this dataset only.
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