Elamipretide Wins FDA Orphan Drug Status, Phase 2 Trial Starts

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by Patricia Inácio, PhD |

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elamipretide designated orphan drug | Friedreich's Ataxia News | announcement illustration of woman with megaphone

Stealth BioTherapeutics’ lead candidate elamipretide has been granted orphan drug status by the U.S. Food and Drug Administration (FDA) for the treatment of Friedreich’s ataxia (FA).

An orphan drug designation seeks to encourage therapies for rare diseases, through benefits such as seven years of market exclusivity upon approval and exemption from FDA fees.

“We are pleased that the FDA has recognized the high unmet need for innovative treatments for Friedreich’s ataxia,” Reenie McCarthy, Stealth’s CEO, said in a press release.

Meanwhile, a Phase 2a trial testing elamipretide in FA patients has started at the Children’s Hospital of Philadelphia (CHOP), under the supervision of David Lynch, MD, PhD, the company announced.

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The trial will enroll 16 FA patients who have experienced vision loss and/or heart disease. Participants will receive one of two doses — high or low — of elamipretide. The goal is to assess the therapy’s safety, as well as changes in visual and cardiac function, with the results used to design a further, pivotal clinical trial.

“We are delighted to be working closely with Dr. Lynch and the Children’s Hospital of Pennsylvania to evaluate elamipretide as a potential treatment for the progressive visual dysfunction and cardiomyopathy that affects visual quality of life and lifespan for individuals affected with this disease,” McCarthy said.

FA is caused by mutations in the FXN gene, which contains the instruction for a protein called frataxin. The frataxin protein is important for the proper working of mitochondria, the cell’s power houses.

Impaired mitochondria function can lead to an abnormally high rate of reactive oxygen species (ROS). In excess, ROS damages cells and can trigger their death, which contributes to FA progression.

Patients with FA often develop a progressive decline in their visual acuity, or sharpness of vision. Heart muscle disease (cardiomyopathy) also is common, affecting more than 90% of patients and worsening with time.

Elamipretide was designed to boost mitochondria function by binding and shielding from damage cardiolipin, a fat-like molecule (lipid) that localizes at the mitochondria’s inner membrane. Cardiolipin is important in the maintenance of proper mitochondria structure and is particularly susceptible to oxidative damage, a result of excess ROS levels relative to antioxidant defenses.

Tests in FA patient-derived cells showed that elamipretide alleviated oxidative stress, increased frataxin levels, and boosted the activity of certain iron-sulfur-containing enzymes that are important for mitochondria.

The therapy also improved several mitochondrial properties, including their shape and structure.

Elamipretide also is being investigated for heart disease associated with two other disorders, Duchenne muscular dystrophy and Barth syndrome. Stealth also is assessing its potential for people with eye diseases associated with impairments in mitochondria, including Leber’s hereditary optic neuropathy and age-related macular degeneration, the leading cause of vision loss in people older than 60.