About nHCM

What is non-obstructive hypertrophic cardiomyopathy (nHCM)

Hypertrophic cardiomyopathy (HCM) is a chronic heart disease in which the abnormally thickened (hypertrophied) heart muscle (myocardium) prevents the heart from pumping blood efficiently (cardiomyopathy).

Non-obstructive hypertrophic cardiomyopathy (nHCM) is a condition that may occur in people who have HCM. Non-obstructive HCM is a condition in which the heart muscle becomes abnormally thickened, which can sometimes impair the blood flow out of the heart, and the heart muscle works harder to pump blood to the body (increased heart pumping function).

Patients diagnosed with nHCM may not exhibit symptoms in the early stages of the condition but may develop them over time, including signs and symptoms that can disrupt daily life, such as:

• chest pain
• dizziness
• shortness of breath
• fainting, palpitations (a sensation of rapid fluttering or pounding heartbeat)
• heart murmurs (unusual sound heard during heartbeat, extra beats or whooshing/swishing sounds which may be faint or loud)
• swelling of ankles, legs, abdomen, or veins in the neck.

The severity of these symptoms varies widely between people with nHCM and can even vary day-to-day.

What is ACACIA-HCM?

Clinical trial overview

ACACIA-HCM is a phase 3 clinical trial of aficamten compared to placebo in patients with symptomatic non-obstructive hypertrophic cardiomyopathy.

The clinical trial will compare the effects of aficamten and placebo on a patient’s health status and exercise capacity. The effectiveness of aficamten and placebo will be compared by measuring your heart symptoms, ability to exercise on a treadmill or bicycle (up to your personal best), and looking at the structure of your heart with ultrasound. The safety and tolerability of aficamten at different, increasing dose levels will also be studied. Finally, the study will also measure the amount of aficamten in your blood at various times, and the effect the research medicine may have on your nHCM.

Clinical trial duration

The clinical trial participation will last between 46 weeks (10.5 months) at the shortest, to 82 weeks (19 months) at the longest.

There are 2 parts to the study:

• Part 1: All participants will receive aficamten or placebo and be followed for 36 weeks (8.5 months).
• Part 2: Participants who complete Week 36 will continue with the same treatment until Week 72 or until the last participant in Part 1 completes Week 36.

Clinical trial drug

If the study doctor determines a patient is eligible and the patient agrees to participate, they will receive either aficamten or placebo during the treatment period (but not both) of 36 to 72 weeks. Placebo is identical in appearance to the study medicine but contains no active ingredient.

The study medicine you receive will be determined by chance (i.e., like flipping a coin). Your chance of receiving aficamten will be 1 in 2 (50%) and your chance of receiving placebo will be 1 in 2 (50%).

Study medicine doses:

Participants who receive aficamten may receive one of four different doses (5, 10, 15, 20 mg) over the first 6 weeks. The starting dose will be 5 mg and may increase to 10 mg at Week 2, 15 mg at Week 4, and up to 20 mg at Week 6, depending on how well your heart pumps the blood.

Aficamten is an investigational drug and is not currently approved for use by regulatory agencies like the FDA – its safety and effectiveness has not been established.