Cumberland Pharmaceuticals announced that it has been awarded a $1 million grant by the U.S. Food and Drug Administration (FDA) to support a Phase 2 clinical trial into oral ifetroban as potential treatment of heart disease associated with Duchenne muscular dystrophy (DMD).
The Phase 2 study (NCT03340675), being launched in collaboration with the Vanderbilt University Medical Center, plans to enroll 48 DMD patients, age 7 and older, with evident damage to the myocardium (the heart’s muscular wall).
Participants must have stable cardiac function over the 12 months prior to the study’s start to be eligible. This means that changes in left ventricle ejection fraction (LVEF) — a measure of the heart’s ability to pump blood — during this period should not be greater than 15%, and their LVEF should be 35% or better.
The trial is expected to enroll about 24 boys and men with early stage (LVEF higher than 45%) DMD-associated cardiac disease, and 24 others with more advanced disease (LVEF between 35-45%), regardless of their DMD-causing mutation.
All will be randomly assigned to either a low or high dose of ifetroban, or a matching placebo, once daily for 12 months. Those who complete the study will have to opportunity to roll into an extension study, in which all will be treated with ifetroban.
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At six and 12 months into the study, researchers will evaluate ifetroban’s effectiveness in preventing a decline in LVEF and pulmonary function, and in improving patients’ quality of life. They will also assess the treatment’s safety and tolerability profile, as well as its stability and metabolism inside the body.
The trial, due to open in November, will be conducted at sites across the U.S., including Riley Children’s Hospital, Vanderbilt’s Children’s Hospital, Children’s National Medical Center, University of California Los Angeles, Emory’s Children’s Healthcare of Atlanta, and Nationwide Children’s Hospital.
“As ifetroban may uniquely address the heart failure associated with this deadly disease, we very much appreciate the FDA grant support of our novel treatment for these critically ill patients,” A.J. Kazimi, CEO of Cumberland Pharmaceuticals, said in the release.
Ifetroban is a potent and selective inhibitor of the thromboxane receptor (TPr), preventing fibrosis and an inflammatory response. It was initially developed by Bristol-Myers Squibb as an anti-platelet agent to prevent blood clots (blood thrombus), and was acquired by Cumberland in 2011.
It is believed to be able to stop important molecular signals that mediate inflammation and fibrosis (tissue scaring) mechanisms in the heart, triggered by the loss of dystrophin protein — the hallmark feature of DMD.
Ifetroban’s safety has been demonstrated in more than 25 clinical studies and over 1,300 subjects, Cumberland states in an investor presentation.
Preclinical studies in two mouse models of DMD showed that treatment with ifetroban can improve cardiac function and extend the animal’s lifespan compared to placebo.
Treatment with ifetroban in mice with limb-girdle muscular dystrophy — another type of muscular dystrophy — also showed a potential to prevent fibrosis in cardiac tissue.
These findings were presented by Larry W. Markham, MD, chief of the pediatric cardiology division at Riley Hospital for Children, at the Parent Project Muscular Dystrophy (PPMD) 2019 annual conference that was held in Orlando, Florida.
Supported by these preclinical data, the FDA decided to approve Cumberland’s request to study ifetroban as a potential treatment for heart problems in DMD.
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