Experimental Drug Being Tested in Mitochondrial and Metabolic Disorders, FA

Edison Pharmaceuticals has announced it is conducting a clinical trial of its experimental drug EPI-743 in children with the mitochondrial myopathyLeigh syndrome, and is planning a trial of this compound in Friedreich's ataxia (FA).

EPI-743 is a small-molecule, oral drug that is designed to enter the central nervous system and synchronize (improve) energy generation in mitochondria, the energy-producing subunits in cells. It is being developed by Edison, which is located in Mountain View, Calif., and Utrecht, Netherlands.

The U.S. National Institutes of Health (NIH) also is testing this molecule in a broader range of disorders, including all metabolic diseases of muscle and mitochondrial myopathies.

Edison's Leigh syndrome trial now open

The Leigh syndrome trial is expected to enroll 30 children ages 1 to 12 at four U.S. sites. The sites are in Palo Alto, Calif.; Akron, Ohio; Houston, Texas; and Seattle, Washington.

Prospective participants must:

• have a confirmed genetic mutation associated with Leigh syndrome;
• show moderate disease severity, with documented evidence of disease progression within the previous year;
• must not take coenzyme Q10, vitamins C or E, lipoic acid or idebenone; and
• meet other study criteria.

For details, see:

• A Phase 2B Randomized, Placebo-Controlled, Double-Blind Clinical Trial of EPI-743 in Children with Leigh Syndrome; and
• Safety and Efficacy Study of EPI-743 in Children With Genetically Confirmed Leigh Syndrome.

Or, go to ClinicalTrials.gov, and enter NCT01721733 in the search box. You also can contact Erin Johnson in California at (650) 641-9212 or ejohnson@edisonpharma.com.

FA trial planned, access program closed

Edison also is planning a trial to test the effect of EPI-743 on visual function in people with FA. Study sites are likely to include the University of South Florida in Tampa, Children's Hospital of Philadelphia, and the University of California, Los Angeles.

More information on this trial will be reported as it becomes available.

An earlier Edison study, which allowed access to EPI-743 for patients with a mitochondrial myopathy or FA who were judged to be within 90 days of end-of-life care, is now closed to new participants.

NIH trial opens in metabolic, mitochondrial disorders

The U.S. National Institutes of Health (NIH) in Bethesda, Md., is conducting a trial of approximately 20 children ages 2 to 11 who have a metabolic disease of muscle or a mitochondrial myopathy.

Metabolic muscle diseases in MDA's program include:

• acid maltase deficiency (AMD, Pompe disease, glycogenosis type 2, lysosomal storage disease)
• carnitine deficiency
• carnitine palmityl transferase deficiency (CPT deficiency)
• debrancher enzyme deficiency (Cori or Forbes disease, glycogenosis type 3)
• lactate dehydrogenase deficiency (glycogenosis type 11)
• myoadenylate deaminase deficiency
• phosphofructokinase deficiency (Tarui disease, glycogenosis type 7)
• phosphogylcerate kinase deficiency (glycogenosis type 9)
• phosphogylcerate mutase deficiency (glycogenosis type 10)
• phosphorylase deficiency (McArdle disease, myophosphorylase deficiency, glycogenosis type 5)

Mitochondrial myopathies in MDA's program include:

• Kearns-Sayre syndrome (KSS)
• Leigh syndrome and maternally-inherited Leigh syndrome (MILS)
• Mitochondrial DNA depletion syndrome (MDS)
• Mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS)
• Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
• Myoclonus epilepsy with ragged red fibers (MERRF)
• Neuropathy, ataxia and retinitis pigmentosa (NARP)
• Pearson syndrome
• Progressive external ophthalmoplegia (PEO)

Prospective participants must:

• have clinical findings of a neuromuscular disease with impaired energy production (typical symptoms include poor muscle tone, abnormal muscle tone or seizures);
• have a disorder that is untreatable or poorly treatable;
• be willing to abstain from initiating dietary supplements or nonprescribed medications and from specially fortified foods or beverages; and
• meet other study criteria.

For details, see EPI-743 for Metabolism or Mitochondrial Disorders; or enter NCT01642056 in the search box at ClinicalTrials.gov.

You also can contact Lynne Wolfe in Bethesda, Md., at (301) 443-8577 or wolfela@mail.nih.gov.

About Clinical Trials A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur. MDA has no ability to influence who is chosen to participate in a clinical trial. To learn more, see Learn About Clinical Studies and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to ClinicalTrials.gov.