Entering 2023 With Hope for Targeted Therapies

Volume 23, Issue 1

Many diseases are managed symptomatically. Take angina, for instance. While percutaneous coronary intervention can treat the underlying lesion mechanically, there are many hazards with this procedure, and the long-term results are often suboptimal. As a result, many patients simply take nitroglycerin to palliate symptoms. There are no targeted drug therapies that can reverse coronary atherosclerosis and directly treat the underlying cause of angina.

In this week’s issue of Talking Therapeutics, we explore 2 new drugs that offer hope to patients by directly targeting the underlying mechanism responsible for causing the disease.

Point 1: Building Momentum for Hypertrophic Obstructive Cardiomyopathy

Hypertrophic obstructive cardiomyopathy (HOCM) is a rare genetic disease that causes the myocardium the thicken. Over time, the heart muscle can become so thick that cardiac output is impaired and patients begin to experience symptoms like dizziness and syncope. Eventually, these patients can develop overt heart failure or die from sudden cardiac death.

To date, therapies for HOCM have focused on reducing symptoms. Beta-blockers and calcium channel blockers can improve the physiology of the disease and palliate symptoms, but they do not treat the underlying disease process.

Last year, mavacamten was the first cardiac-myosin inhibitor approved to treat HOCM. This class of medications treats the underlying disease process directly and reduces left-ventricular mass without the need for invasive surgery. This week, a phase 2 study showed a second cardiac myosin inhibitor, aficamten, showed reduction in the left-ventricular outflow track obstruction as well as improvements in heart failure-related symptoms. This study is very relevant as aficamten has more favorable pharmacokinetic features, including shorter half-life, and lacks the significant drug–drug interactions associated with mavacamten.

Point 2: New Hope for Alzheimer Disease?

Alzheimer disease is a progressive neurological disease characterized by memory loss and cognitive impairment. The underlying disease process is deposition of beta-amyloid plaques within the central nervous system. Current therapies only manage symptoms by modulating the levels of neurotransmitters involved in cognition and memory.

Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, was tested in a study published in The New England Journal of Medicine this week. Researchers studied lecanemab vs placebo in nearly 1800 patients with early Alzheimer disease. Lecanemab was associated with reduced markers of amyloid in early Alzheimer disease and moderately less decline in measures of cognition and function at 18 months, compared to placebo.

Unfortunately, drug-related side effects were frequent with lecanemab, suggesting longer-duration trials are needed to fully elucidate the potential of this new therapy.