Stealth Bio Faces Setback in Failed Mitochondrial Disease Trial

Boston-based Stealth Biotherapeutics reported that its Phase III MMPOWER-3 clinical trial of elamipetride failed to meet its primary endpoint. The trial was evaluating the effectiveness of elamipetride in patients with primary mitochondrial myopathy (PMM).

PMMs are a group of disorders associated with abnormalities in the DNA of mitochondria (mtDNA) or in genes outside the mitochondria. The primary affect the skeletal muscle. Mitochondria are the engines of energy in the cells. Problems with mitochondria often affect the ability of cells to break down food and oxygen and produce energy.

The primary endpoints for the MMPOWER-3 trial were changes in the six-minute walk test and Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score. The drug was well tolerated, and most adverse events were mild to moderate.

“We are deeply grateful to our patients and families, our investigators and their teams, and our advocacy partners for their support of this study, and share their disappointment that it did not meet the promise of our earlier trials in this indication,” said Reenie McCarthy, chief executive officer of Stealth. “We remain confident in the promise of our platform and committed to our mission of improving the lives of people living with diseases involving mitochondrial dysfunction.”

The company plans to meet with the U.S. Food and Drug Administration in early 2020 to discuss its Barth syndrome program, where, McCarthy said, “we have observed significant improvement in cardiac stroke volume during open-label extension, and continue to enroll our Phase IIb clinical trial in geographic atrophy associated with dry age-related macular degeneration, in which we observed improvement in visual function during an earlier Phase I study. We are also progressing our pipeline of second-generation mitochondrial therapeutics, with lead pipeline compound SBT-272 entering Phase I.”

Barth syndrome is a rare illness marked by an enlarged and weakened heart, muscle weakness, recurrent infections because of lower white blood counts, and short stature. It is almost exclusively observed in males.

Barth is caused by mutations in the TAZ gene. The TAZ gene codes for the tafazzin protein, which is located inside the mitochondria. Tafazzin alters a fat called cardiolipin, which plays significant roles in the inner membrane of the mitochondria.

In October, Stealth inked a deal with Alexion Pharmaceuticals to co-develop and commercialize elamipretide for mitochondrial diseases. Alexion has the opportunity to exercise the option after the delivery of the MMPOWER-3 results.

That could be in trouble given the failure of this trial, unless the companies see something promising in the data or for other applications for the drug. The option deal is also for elamipretide for Barth syndrome and Leber’s hereditary optic neuropathy (LHON).

Alexion made an initial $30 million payment to Stealth, including an option fee, an equity investment and funding for development. Should Alexion continue with the option, there will be additional payments and potential regulatory and commercial milestones.

Other Stealth assets, including SBT-272, are not included in the option. SBT-272 is a mitochondrial targeting investigational drug in preclinical development for rare neurodegenerative diseases. In October, the company presented preclinical data demonstrating that treatment with the drug was linked to dose-dependent delay in the onset of neurological disease in a mouse model of amyotrophic lateral sclerosis (ALS), showing both a decrease of neurodegenerative markers and prolonged lifespan.