Cytokinetics, Incorporated (Nasdaq: CYTK) today announced new data
at CMR 2024 demonstrating favorable effects on cardiac structure,
function and fibrosis related to treatment with aficamten in
FOREST-HCM (
Follow-up,
Open-Label,
Research
Evaluation of
Sustained
Treatment with Aficamten in
HCM),
the open label extension clinical trial of aficamten in patients
with hypertrophic cardiomyopathy (HCM).
In many patients with HCM, the left ventricular
hypertrophy that characterizes the disease results in elevated
cardiac mass, and left ventricular outflow tract (LVOT) obstruction
is often accompanied by mitral valve regurgitation. Patients with
HCM may also present with myocardial fibrosis, a strong predictor
of abnormal cardiac rhythm and sudden death, and other cardiac
structural abnormalities such as increased left atrial volume.
Previously presented data from FOREST-HCM showed that prolonged
treatment with aficamten was associated with sustained reductions
in LVOT gradients with no treatment interruptions for low left
ventricular ejection fraction (LVEF) due to aficamten, as well as
sustained reductions in cardiac biomarkers and improved
symptoms.
New data presented today from the cardiac
magnetic resonance (CMR) sub-study in FOREST-HCM show that
treatment with aficamten for 48 weeks resulted in favorable cardiac
structural remodeling, improvements in cardiac function, and
stabilization of myocardial fibrosis. At the time of this analysis,
16 patients in FOREST-HCM had completed a CMR at baseline and at
Week 48. Baseline characteristics of the CMR cohort were comparable
to the overall patient population in FOREST-HCM. In this trial,
treatment with aficamten for 48 weeks resulted in statistically
significant improvements in measures of cardiac structure and
function including left ventricular mass index (-11.4 g/m2 ±19.4,
p=0.03), maximum left ventricular septal wall thickness (-1.3 mm
±1.8, p=0.02), left atrial volume (-16.3 ml/m2 ±26.4, p=0.05), and
mitral regurgitant volume (-12.9 ml ±15.1, p=0.01) and fraction
(-9.5% ± 15.1, p=0.05). Additionally, treatment with aficamten
stabilized interstitial and replacement myocardial fibrosis, with
no increase in the fibrosis mass, as measured by absolute mass of
late gadolinium enhancement (-0.6 g ± 5.0, p=0.64).
“These are the first long-term CMR data to
emerge from FOREST-HCM, and they demonstrate potential disease
modifying effects of aficamten in patients with obstructive HCM,”
said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice
President of Research & Development. “Added to the existing
body of evidence from both FOREST-HCM and SEQUOIA-HCM, the pivotal
Phase 3 clinical trial of aficamten in oHCM, these data further
support the profile of aficamten as a potential next-in-class
cardiac myosin inhibitor that is not only associated with
statistically significant and clinically meaningful improvements to
hemodynamics and symptoms, but that improves the architecture of
the heart. We look forward to expanding on these data in the
future.”
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.
About the Broad Phase 3 Clinical Trials
Program for Aficamten
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.
SEQUOIA-HCM (Safety,
Efficacy, and Quantitative
Understanding of Obstruction
Impact of Aficamten in
HCM), was the pivotal Phase 3 clinical trial in
patients with symptomatic obstructive hypertrophic cardiomyopathy
(HCM). The results from SEQUOIA-HCM show that treatment with
aficamten significantly improved exercise capacity compared to
placebo, increasing peak oxygen uptake (pVO2) measured by
cardiopulmonary exercise testing (CPET) by a least square mean
difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002).
The treatment effect with aficamten was consistent across all
prespecified subgroups reflective of patient baseline
characteristics and treatment strategies, including patients
receiving or not receiving background beta-blocker therapy.
Statistically significant (p<0.0001) and clinically meaningful
improvements were also observed in all 10 prespecified secondary
endpoints. Aficamten was well-tolerated with an adverse event
profile comparable to placebo. Treatment emergent serious adverse
events occurred in 8 (5.6%) and 13 (9.3%) patients on aficamten and
placebo, respectively. Core echocardiographic left ventricular
ejection fraction (LVEF) was observed to be <50% in 5 patients
(3.5%) on aficamten compared to 1 patient (0.7%) on placebo. There
were no instances of worsening heart failure or treatment
interruptions due to low LVEF.
Aficamten is currently the subject of two
ongoing Phase 3 clinical trials: MAPLE-HCM
(Metoprolol vs Aficamten in
Patients with LVOT Obstruction on
Exercise Capacity in HCM),
evaluating aficamten as monotherapy compared to metoprolol as
monotherapy in patients with obstructive HCM, and ACACIA-HCM
(Assessment Comparing
Aficamten to Placebo on Cardiac
Endpoints In Adults with
Non-Obstructive HCM), evaluating aficamten in
patients with symptomatic non-obstructive 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.
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 in the
U.S., however, there are an estimated 400,000-800,000 additional
patients who remain undiagnosed.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 first-in-class muscle activators and
next-in-class muscle inhibitors 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 interactions 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. Aficamten is also currently being evaluated in two
ongoing Phase 3 clinical trials: MAPLE-HCM, evaluating aficamten as
monotherapy compared to metoprolol as monotherapy in patients with
obstructive HCM and ACACIA-HCM, evaluating aficamten in patients
with non-obstructive HCM. Cytokinetics is also developing omecamtiv
mecarbil, a cardiac muscle activator, in patients with heart
failure. Additionally, Cytokinetics is developing CK-136, a cardiac
troponin activator for the potential treatment HFrEF and other
types of heart failure, such as right ventricular failure,
resulting from impaired cardiac contractility, and 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 and 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. 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 CYTOKINETICS and C-shaped logo are
registered trademarks of Cytokinetics in the U.S. and certain other
countries.
Contact:Cytokinetics Diane WeiserSenior Vice President,
Corporate Communications, Investor Relations(415) 290-7757
References:
- 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
- Symphony Health 2016-2021 Patient Claims Data DoF;
- 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.
- 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.
- 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
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