About Perhexiline


Perhexiline is a carnitine palmitoyl transferase (“CPT”) inhibitor being developed by Heart Metabolics to treat symptoms in patients with HCM.

The heart preferentially uses fatty acids as fuel for producing most of its energy. While this process provides a steady and reliable fuel source, it is an inefficient process in terms of its oxygen consumption when compared to glucose as a fuel. Perhexiline blocks the uptake of fatty acids by the heart, causing the heart to switch to glucose as a fuel source—a more energy efficient process.


The heart uses fatty acids as its preferred source of fuel for energy production. The oxygen requirement for this process is not a problem for a healthy heart.


HCM affected hearts require greater amounts of energy than normal hearts, and this difference is exaggerated during exercise. As a result, the supply of oxygen is unable to meet the demand imposed by consuming fatty acids for energy production. This causes a rise of calcium inside the cell, which stimulates even more hypertrophy and may predispose the heart to arrhythmia. Reduced energy production is associated with severe limitations in exercise tolerance.


Perhexiline blocks fatty acid use for energy production,  forcing the heart to use glucose instead.  This process consumes less oxygen and reverses the energy deficit in HCM. Perhexiline also prevents the rise in calcium inside the cell which may have other beneficial effects.

(Click a graphic above for more information.)

This improved efficiency in oxygen consumption results in improved myocardial energetics, reducing or even normalizing the energy imbalance created by the genetic defect. These benefits have been shown to translate into improved clinical outcomes for symptomatic patients with HCM. Patients treated with perhexiline have been shown to have reduced symptoms, improved exercise time, and improved peak oxygen consumption when compared to patients treated with placebo.

Perhexiline also affects the pattern of electrical flow across heart cell membranes in a favorable way through its effect on the passage of ions such as calcium, sodium and potassium.

Since myocardial energy imbalance and calcium inside the heart cell are the likely stimuli for hypertrophy, it is hoped that perhexiline treatment of symptomatic patients with HCM may delay, prevent or even reverse progression of disease.

History of Perhexiline: An old drug for a new indication

Perhexiline was originally developed and approved in the 1970s as a treatment for angina pectoris, which is chest pain or discomfort caused when the heart muscle does not receive enough oxygen-rich blood. While the drug was approved in several countries, including the United Kingdom, France, Australia and New Zealand, perhexiline was never approved in the U.S. After perhexiline was on the market for several years, it was discovered that a small number of patients using the drug developed unexplained severe liver and nerve toxicity. As a result, perhexiline was withdrawn from Europe in 1985, but continued to be available in Australia and New Zealand.  The cause of this toxicity is now understood and is due to the accumulation of the drug over a prolonged period of time in a small percentage of patients who have a genetic mutation that causes them to be slow metabolizers of perhexiline. This toxicity has been shown to be completely preventable through the use of simple genetic testing before starting treatment with perhexiline, and by measuring plasma levels of perhexiline periodically after starting treatment with the drug (and adjusting the dose, as necessary).

Perhexiline has been used safely in Australia and New Zealand for more than twenty years. For example, in Australia, with the use of genetic testing and plasma level monitoring, the toxicity has been eliminated in Australia where more than 100,000 patient-years of exposure have been recorded.

In recent years, there have been a number of clinical trials with perhexiline in patients with HCM, chronic heart failure and ischemia. These studies have shown promising results in these additional cardiovascular diseases, with statistically significant improvements in exercise capacity and cardiac energetics, while also providing symptom relief.

Development Timeline

Phase 3


Scheduled to start in 2017. Expected to enroll about 300 patients with HCM for about two years in 100 centers in the US and internationally.

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Phase 2

Q2 2016 - Q4 2016

Ongoing, and expects to enroll 33 patients with HCM for four months of treatment in ten US centers. Study will evaluate efficacy at a low dose for two months, followed by a higher dose for two months.

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Novel Monitoring Assay

Q1 2016 - Q2 2016

Heart Metabolics develops a novel companion in vitro diagnostic for monitoring plasma perhexiline concentrations during treatment.

Phase 1 – TQT


Heart Metabolics completes a thorough QT (TQT) study in patients and a series of studies on heart muscle cells and tissue. These studies demonstrate a pattern of significant effects which help to explain some of the benefits which are seen in HCM patients.

Agreement on SPA

Q2 2015

Heart Metabolics and FDA reach agreement on a Special Protocol Assessment (SPA). This will be a single clinical trial of about 350 patients in which we seek to demonstrate the benefits of perhexiline in HCM patients.

Academic Clinical Study

An exploratory study of 46 HCM patients shows that patients treated with perhexiline have improvement in their ability to exercise over a period of 6 months, while patients who did not receive perhexiline continued to decline.

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