Cytokinetics Presents Baseline Characteristics From SEQUOIA-HCM at the HCM Society Scientific Sessions
“The baseline characteristics of SEQUOIA-HCM show that the patients enrolled into this pivotal trial align with our objectives for aficamten, which include assessing our next-in-class cardiac myosin inhibitor in a population with substantial deficit in exercise capacity and significant symptom burden despite background treatment with guideline directed medical therapies,” said
SEQUOIA-HCM: Baseline Characteristics
SEQUOIA-HCM was designed to evaluate aficamten in patients with symptomatic obstructive HCM on background medical therapy over a 24-week period. Patients enrolled in SEQUOIA-HCM were required to have severe left ventricular outflow tract (LVOT) obstruction as evidenced by a resting LVOT-G ≥30 mmHg, a post-Valsalva peak LVOT-G ≥50 mmHg, NYHA functional class II or III, and a peak VO2 ≤90% predicted.
SEQUOIA-HCM enrolled a total of 282 patients, with one third from
|Table 1. Baseline Characteristics of Patients in SEQUOIA-HCM|
|Baseline Characteristics (N=282)||n (%) or Mean (SD)a|
|Age, years||59.1 (12.9)|
|Weight, kg||81.6 (15.7)|
|Body mass index, kg/m2||28.1 (3.7)|
|Systolic blood pressure, mmHg||125.3 (16.1)|
|Diastolic blood pressure, mmHg||74.4 (10.6)|
|Heart rate, bpm||65.6 (11.2)|
|History of known HCM-causing gene mutation||48 (17.0)|
|Positive family history of HCM||71 (25.2)|
|Time since initial HCM diagnosis, median (IQR), years||4.3 (1.7 – 8.5)|
|HCM medical therapies:|
|Non-dihydropyridine calcium channel blocker||75 (26.6)|
|NYHA functional class II / III / IV||214 (75.9) / 67 (23.8) / 1 (0.4)|
|SRT guideline eligiblec||68 (24.1)|
|Permanent atrial fibrillation||1 (0.4)|
|Paroxysmal atrial fibrillation||40 (14.2)|
|Peak VO2, mL/kg/min||18.5 (4.5)|
|Peak VO2, % of predicted maximum1||56.9 (11.8)|
|Total workload, watts||122.4 (41.3)|
|hs-cTnI, median (IQR), ng/L||12.1 (7.7 – 27.3)|
|a Unless otherwise indicated.
b >100% total due to overlap in ethnicity and race.
c NYHA FC III and any LVOTO ≥50 mmHg.
d Combines hypertension and essential hypertension.
e Combines T2DM, T1DM, and DM.
CCB, calcium channel blocker; DM, diabetes mellitus, including types 1 and 2; IQR, interquartile range
About Aficamten and the Broad Phase 3 Clinical Trials Program
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 is currently the subject of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial 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), a pivotal Phase 3 clinical trial in patients with symptomatic non-obstructive HCM. Results from SEQUOIA-HCM are expected by the end of 2023. Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the
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
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 announce the results of SEQUOIA-HCM by the end of 2023. 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
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