Harvard and MGH’s Jim Januzzi, MD describing Cytokinetics’s SEQUOIA-HCM aficamten trial.

Cardiology Pharmaceuticals

Cytokinetics’s Aficamten Delivers in SEQUOIA-HCM Trial

Topline results from Cytokinetics’ SEQUOIA-HCM phase 3 trial suggest that 2024 could be the company’s best year ever, showing that its investigative obstructive hypertrophic cardiomyopathy (HCM) drug aficamten significantly improved all primary and secondary endpoints.

• HCM causes the heart muscle to become abnormally thick, limiting the heart’s pumping function and leading to reduced exercise capacity, a range of other symptoms, and greater risks of severe CV complications.
• Aficamten is a selective cardiac myosin inhibitor that treats HCM by reducing active actin-myosin bridges during each cardiac cycle, thus suppressing myocardial hypercontractility associated with HCM.

SEQUOIA-HCM had all the makings of a well-design trial (randomized, placebo-controlled, double-blind, multicenter, international) and appears to have achieved similarly powerful improvements among its 282 participants over 24 weeks of treatment:

• Aficamten significantly improved exercise capacity versus placebo, increasing peak oxygen uptake by a least square mean difference of 1.74 mL/kg/min (the primary endpoint). 
• The drug achieved statistically significant and clinically meaningful improvements across all 10 secondary endpoints, including KCCQ-CSS, NYHA, LVOT-G, and proportion of patients at <30 mmHg.
• Aficamten proved to be well-tolerated, with similar adverse events as the placebo, and no instances of worsening heart failure or treatment interruptions due to low LVEF.

These results were consistent across all patient subgroups, including patients with various baseline characteristics and treatment strategies, and patients receiving or not receiving background beta-blocker therapy.

The SEQUOIA-HCM results are further supported by aficamten’s phase 2 REDWOOD-HCM trial, which showed similarly significant improvements versus placebo through 10 weeks.

• They also reportedly compared favorably to Bristol Myers Squibb’s Camzyos, which is the only drug with FDA approval for obstructive HCM.

It’s safe to say that SEQUOIA-HCM’s topline results raised excitement on both the clinical and business sides of the HCM community.

• HCM clinicians praised the results and highlighted the need for more HCM treatment options
• Cytokinetics’s stock price shot up over 80% to $83, marking a 19-year high and adding $3.74B to its market cap
• Reports of big pharma companies considering acquiring Cytokinetics reemerged

However, aficamten still has to achieve regulatory approval, which Cytokinetics plans to seek in the second half of 2024. 

Takeaway

The topline SEQUOIA-HCM results seem to suggest that a new and potentially more effective treatment option for symptomatic obstructive HCM is on the way, which could prove to be a big deal for the 680k to 1.1M HCM patients in the U.S and a very big deal for the Cytokinetics.

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The Wire

• The AED Bystander Effect: The latest cardiology study to earn mainstream headlines highlighted the low use of automated external defibrillators (AEDs) at athletic facilities, even in states where they’re mandated, suggesting that we’ll need more than laws to increase bystanders’ AED use. An analysis of over 9k out-of-hospital cardiac arrest cases at recreational facilities found that only 19% of patients had an AED applied by a bystander in states requiring AEDs, roughly matching states where AEDs aren’t legally required.

• First Partial Heart Transplant’s 1-Year Milestone: The first world’s first partial heart transplant, performed by a Duke team on a newborn in 2022 remained successful after one year. The partial heart transplant used only the aortic and pulmonary valves from a donor heart that didn’t qualify for a full transplant, and required only one quarter of the immunosuppressants. Although more follow-up is needed, these results suggest that this technique could significantly expand access to transplants while reducing the side effects of long-term immunosuppressant use.

• Survival Shifts Over Time in ViV-TAVR vs. Redo SAVR: A recent meta-analysis in the American Journal of Cardiology revealed that ViV-TAVR has a short-term survival advantage versus redo SAVR (HR=0.58) within the first 6 months. However, beyond 6 months ViV-TAVR was associated with a higher risk of all-cause mortality (HR=1.92). The analysis of data from 16 observational studies and nearly 4,400 patients emphasized the importance of optimal valve size to ensure ViV-TAVR success.

• Philips BioTelemetry’s False Claims Fine: Philips’ ECG monitoring company BioTelemetry, and its subsidiary LifeWatch Services will pay $14.7M to resolve false claims allegations related to remote cardiac monitoring. The U.S. alleged that between 2014 and 2020, LifeWatch’s portal design and clinical training processes caused providers to unwittingly select telemetry monitoring, which has the highest reimbursement rates of any ECG monitoring service. LifeWatch also allegedly disregarded written notes from clinic personnel that specifically mentioned plans to use monitoring levels with lower reimbursements.

• CardioMech Funding: Mitral valve repair startup CardioMech raised another $13M (total raised $42M) to advance its therapy for degenerative mitral regurgitation. The CardioMech device is a catheter-based artificial chord designed to reduce or eliminate mitral regurgitation and to restore the native anatomy, which the company believes could reduce the need for open-heart surgery and may lessen the need for watchful waiting in younger and healthier patients.

• ICD Implant Appropriateness Gaps: A Heart Rhythm Journal analysis revealed potential gaps between ICD implant clinical guidelines and reimbursements. Among 300k ICDs implanted in the U.S. between April 2018 and March 2019, 95% of mappable implants were deemed appropriate and less than 2% fell into the “rarely appropriate” category. However, roughly 100k of the implants that were considered “appropriate” based on appropriate use criteria but were excluded by CMS’ national coverage determination.

• LUMA Vision Funding: 4D cardiac imaging and navigation platform startup LUMA Vision scored $22M in Series A3 financing that it will use to seek FDA clearance, prepare for its U.S. commercialization, and fund future product development. LUMA Vision’s end-to-end VERAFEYE platform combines an ultrasound-enabled catheter sensor with digital imaging and deep learning technologies to provide 360-degree imagery of the beating heart and surrounding anatomy to support AFib and structural heart procedures.

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• Colchicine Misses in Afib Prevention: In a study of 199 AFib patients post-ablation, those who had a short course of the anti-inflammatory drug colchicine (0.6 mg twice daily for 10 days) had similar rates of atrial arrhythmia recurrence as placebo-takers after two weeks (31% vs. 32%) and at three months (14% vs. 15%). After 1.3 years, colchicine didn’t reduce a composite of ER visits, CV hospitalization, cardioversion, or repeat ablation (29 vs. 25 per 100 patient-years). 

• Nurea’s New Platform Partners: French cardiovascular CT AI developer Nurea closed 2023 with a bang, announcing that the AI platform companies Blackford Analysis and deepc will carry its PRAEVAorta 2 application. Nurea’s flagshipPRAEVAorta 2 solution provides automated reconstruction and analysis of the arterial tree, with the goal of allowing faster diagnosis within standard imaging workflows.

• Breaking the Rhythm in Patients with HFpEF and AFib: In a study of 1,034 patients with HFpEF and concurrent AFib, the maintenance of sinus rhythm through catheter ablation showed a 45% reduction in the risk of death or rehospitalization for worsening heart failure over a median of 39 months. Patients who underwent ablation also exhibited a noteworthy 33% decrease in atrial tachycardia/AFib recurrence compared to those who didn’t.

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The Resource Wire

• TeraRecon’s Structural Heart Enhancements: Detecting and addressing mitral valve and LAA conditions can be challenging. Check out TeraRecon’s Structural Heart white paper and discover how improving workflow and pretreatment planning can streamline these processes and potentially improve patient outcomes.

• Cleerly Transforms Personalized CVD Care: Cleerly is launching perhaps the first large-scale randomized imaging AI trial, as it seeks to prove that AI-guided cardiovascular care reduces heart attacks. The five year TRANSFORM trial will investigate whether CVD patients who receive treatments based on results from Cleerly’s investigational AI-based plaque staging system have better outcomes.

• PIA Medical Processes It All: Need an analysis like calcium scoring, strain or even FFR? PIA Medical began as a Core Lab and can handle creative cardiac research and clinical trials along with the full breadth of clinical analyses available today.

• Cardiovascular Structured Reporting Adoption Benefits: Check out this Change Healthcare report detailing the benefits of cardiovascular structured reporting, and how to drive structured reporting adoption in your own organization.

• Us2.ai’s Heart Failure Screening Impact: See how Us2.ai’s echo AI solution improved heart failure screening in the NHS, reducing echo waiting times from 12 months to under 6 weeks.