Stealth BioTherapeutics Announces Positive Results for Elamipretide in Barth Syndrome Open-Label Extension Trial

Date : April 16, 2019

BOSTON, April 16, 2019 /PRNewswire/ -- Stealth BioTherapeutics (NASDAQ: MITO), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced positive results from the open-label extension of the Phase 2/3 TAZPOWER study of elamipretide, an investigational drug, in patients with genetically confirmed Barth syndrome. Barth syndrome is an ultra-rare mitochondrial disease in which reduced levels of the mitochondrial phospholipid cardiolipin are associated with skeletal muscle weakness, debilitating fatigue, cardiac abnormalities, recurrent infections, delayed growth and reduced life expectancy. The TAZPOWER open-label results, presented at the 2019 MDA Clinical & Scientific Conference, demonstrated potential for elamipretide to improve the relative levels of normal to abnormal cardiolipin which are diagnostic for the disease, as well as measures of exercise performance and patient-reported outcomes.

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"These Phase 2/3 results support previous pre-clinical findings suggesting that elamipretide may help improve cardiolipin levels," said Dr. Hilary Vernon, TAZPOWER trial investigator, Associate Professor of Pediatrics at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine and Director, Barth Syndrome Clinic at Kennedy Krieger Institute, Baltimore, MD. "Based on the correlation of the cardiolipin ratio with disease severity, these changes in the cardiolipin ratio data may suggest that elamipretide has the potential to modify the course of disease in Barth syndrome rather than merely addressing the symptoms." 

TAZPOWER was a Phase 2/3 crossover study of elamipretide in 12 patients with Barth syndrome followed by an open-label extension in which 10 of the 12 patients participated. Although statistical significance was not achieved in the intent-to-treat population during the blinded, placebo-controlled portion of the study, a pre-specified analysis of subjects with relatively higher levels of normal cardiolipin showed improvement on several endpoints. 

Today's presentation of the open-label extension data, demonstrating improvements in various endpoints irrespective of baseline cardiolipin levels, suggests that a longer duration of elamipretide therapy is particularly important for patients with lower baseline levels of normal cardiolipin. Overall, a significant (almost 40%) decrease in the average ratio of abnormal to normal cardiolipin was observed from the start of the study to week 12 of the open-label extension. 

Additionally, significantly increased exercise performance in the Six Minute Walk Test (6MWT) was observed both in patients with relatively more normal cardiolipin as well as in those with relatively less normal cardiolipin.  Reductions in fatigue, measured through the BarTH Syndrome Symptom Assessment (BTHS-SA) tool, a novel patient-reported outcome assessment measure, were also observed, with greater improvements observed with longer duration of elamipretide treatment. Improvements were also seen across additional secondary and exploratory endpoints including functional assessments and patient-reported outcomes.

Patients reported improvements in various symptoms, including fatigue/energy levels (90% of patients reported improvement), stamina/endurance (90%), muscle strength (80%) and appetite (70%). In addition, most patients reported improvement in daily life activities (90%), physical activities (90%) and quality of life (80%).

"Our patient community is in dire need of a therapy that addresses the complex, multi-system challenges that occur in Barth syndrome," said Emily Milligan, Barth Syndrome Foundation Executive Director. "The positive findings presented today that elamipretide may improve fatigue and overall quality of life for people living with this devastating disease are encouraging that a potential therapy could finally be on the horizon." 

In the placebo-controlled and open-label extension portions of the study, most adverse events were mild to moderate in severity. The most commonly reported adverse events included injection site reactions.

"We are encouraged by these signals that elamipretide may benefit individuals affected by the severe cardiolipin deficiency characteristic of Barth syndrome, which we believe to be one of the most challenging mitochondrial diseases for elamipretide due to reduced opportunity for elamipretide to engage with its target, cardiolipin," said Reenie McCarthy, Chief Executive Officer of Stealth BioTherapeutics. "These findings, which align with the improvements in activities of daily living reported by TAZPOWER subjects in our patient and caregiver perception of change video protocols, will inform our upcoming discussions on a regulatory path forward."

The U.S. Food and Drug Administration (FDA) has granted Fast Track and Orphan Drug designations for elamipretide for the treatment of Barth syndrome. Last summer, the Barth Syndrome Foundation (BSF) hosted a patient-focused drug development meeting with the FDA, from which the organization published a Voice of the Patient Report. The BSF recently shared the report with the FDA during a Professional Affairs and Stakeholder Engagement meeting.

For additional information on the TAZPOWER study or elamipretide, please refer to Stealth's website and

About the TAZPOWER Study

TAZPOWER is a Phase 2/3 crossover study evaluating the effects of daily subcutaneous (SC) treatment with elamipretide in 12 patients with genetically confirmed Barth syndrome followed by an open-label treatment extension. Part 1 was a 28-week crossover trial of patients randomized to elamipretide 40 mg SC daily for 12 weeks, followed by SC placebo daily for 12 weeks, or vice versa, separated by a 4-week washout. Part 2 is an open-label assessment for up to 168 weeks of functional, patient-reported outcomes, and safety/tolerability.

The primary endpoints included change in distance walked during the 6MWT and change in the BTHS-SA Total Fatigue score. Secondary endpoints included additional functional assessments, patient-reported outcomes and safety/tolerability.

About Barth Syndrome

Barth syndrome is an ultra-rare genetic condition characterized by muscle weakness, cardiac abnormalities often leading to heart failure, recurrent infections, delayed growth, and reduced life expectancy. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 300,000 to 400,000 individuals worldwide at birth. There are currently no FDA-approved therapies for patients with Barth syndrome.

About Stealth

We are a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction. Mitochondria, found in nearly every cell in the body, are the body's main source of energy production and are critical for normal organ function. Dysfunctional mitochondria characterize a number of rare genetic diseases, collectively known as primary mitochondrial diseases, and are also involved in many common age-related diseases. We believe our lead product candidate, elamipretide, has the potential to treat both rare genetic and common age-related mitochondrial diseases. We are studying elamipretide in the following primary mitochondrial diseases: primary mitochondrial myopathy, Barth syndrome and Leber's hereditary optic neuropathy. We are also studying elamipretide in dry age-related macular degeneration. Our other pipeline candidates include SBT-20, which we are evaluating for rare peripheral neuropathies, and SBT-272, which we are evaluating for rare neurodegenerative disease indications. We have optimized our discovery platform to identify novel mitochondrial-targeted compounds, which may be nominated as therapeutic product candidates or utilized as scaffolds to deliver other compounds to mitochondria. Our mission is to be the leader in mitochondrial medicine, and we have assembled a highly experienced management team, board of directors and group of scientific advisors to help us achieve this mission.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Stealth BioTherapeutics' plans, strategies and expectations for its preclinical and clinical advancement of its drug development programs, including its ongoing clinical trials of elamipretide for the treatment of Barth syndrome. Statements that are not historical facts, including statements about Stealth BioTherapeutics' beliefs, plans and expectations, are forward-looking statements. The words "anticipate," "expect," "hope," "plan," "potential," "possible," "will," "believe," "estimate," "intend," "may," "predict," "project," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Stealth BioTherapeutics may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements as a result of known and unknown risks, uncertainties and other important factors, including: Stealth BioTherapeutics' ability to obtain additional funding; the ability to successfully demonstrate the efficacy and safety of Stealth BioTherapeutics' product candidates and future product candidates; the preclinical and clinical results for Stealth BioTherapeutics' product candidates, which may not support further development and marketing approval; the potential advantages of Stealth BioTherapeutics' product candidates; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, which may affect the initiation, timing and progress of preclinical studies and clinical trials of Stealth BioTherapeutics product candidates; Stealth BioTherapeutics' ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Stealth BioTherapeutics' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Stealth BioTherapeutics' most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission ("SEC"), as well as in any future filings with the SEC. Forward-looking statements represent management's current expectations and are inherently uncertain. Except as required by law, Stealth BioTherapeutics does not undertake any obligation to update forward-looking statements made by us to reflect subsequent events or circumstances. 

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