Bendavia (elamipretide SC) / Stealth BioTherapeutics - LARVOL DELTA

Initial Psychometric Evaluation of the Barth Syndrome Symptom Assessment (BTHS-SA) for Adolescents and Adults in a Phase 2 Clinical Study. (PubMed, Orphanet J Rare Dis) - P2/3 | "Though the small sample size limits strong conclusions, this analysis suggests the BTHS-SA can produce reliable scores upon which valid inferences may be drawn. The BTHS-SA may be a useful tool to evaluate treatment benefits in this underserved population."

Clinical • Journal • P2 data • Fatigue • Myositis • TAFAZZIN

Significantly Improved Cardiac Function in Neonate with Barth Syndrome on Investigational Drug Elamipretide (ISHLT 2025) - "He was discharged home on oral heart failure medications and subcutaneous elamipretide...Barth syndrome is an X-linked recessive mitochondrial disorder arising from pathogenic variants in the TAFAZZIN gene, encoding a transacylase in the inner mitochondrial that catalyzes final processing and maturation of cardiolipin, which is important for high energy-requiring tissues such as cardiac muscle. Elamipretide is an investigational drug that stabilizes cardiolipin, resulting in mitochondrial membrane stabilization.Summary Our neonate with Barth syndrome associated LVNC cardiomyopathy showed remarkable improvement in cardiac function on elamipretide, demonstrating the potential of this medication for patients with this rare syndrome."

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • TAFAZZIN

Cardiac Pathology in a Patient with a Novel Likely Pathogenic Variant C.703del (p.Ile235SerfsTer4) of the TAZ Gene (ISHLT 2025) - "He continues to do well as an outpatient and remains on subcutaneous Elamipretide.Summary We describe a case of Barth syndrome harboring a novel likely pathogenic variant of the TAZ gene exhibiting dilated cardiomyopathy, endocardial fibroelastosis, and prominent mitochondrial abnormalities. Elamipretide is well tolerated and may have temporized the cardiac function to serve as a medical bridge to transplantation."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • TAFAZZIN

Topical bevemipretide (SBT-272) eye drops in development for dry AMD: Phase 1 trial design informed by 13-week GLP study results (ARVO 2025) - "Conclusions Bevemipretide is a reimagined, next-generation small molecule in development for the treatment of dry AMD and follows the foundational studies and mechanism of action of subcutaneous elamipretide...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology

Stealth BioTherapeutics Announces Achievement of 50% Enrollment Target in Phase 3 ReNEW Study of Elamipretide in Patients with Dry Age-Related Macular Degeneration (PRNewswire) - "Stealth BioTherapeutics Inc...today announced that it has achieved its 50 percent enrollment target in the global Phase 3 ReNEW study (NCT06373731) of elamipretide in patients with dry age-related macular degeneration (dry AMD). The total target enrollment is 360 participants. The ReNEW study is evaluating the efficacy, safety, and pharmacokinetics of daily subcutaneous injections of elamipretide – a first-in-class mitochondria-targeted investigational therapeutic – in participants with dry AMD...In addition to the ReNEW study, Stealth will initiate the ReGAIN study – a second global Phase 3 trial in dry AMD – in the coming months. Data from the ReNEW study is expected to be reported in 2026."

Enrollment status • New P3 trial • P3 data • Age-related Macular Degeneration

A Polytherapy Intervention in an Experimental Traumatic Optic Neuropathy Mouse Model. (PubMed, Ophthalmic Plast Reconstr Surg) - "Early combinatorial therapeutic intervention to address disparate molecular pathways following optic nerve trauma effectively halts retinal neurons' progressive structural and functional degeneration."

Journal • Preclinical • Inflammation • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Expanded-access use of elamipretide in a newborn with Barth syndrome: a case report. (PubMed, Eur Heart J Case Rep) - "He was weaned off oxygen completely on DOL49 and discharged home on DOL61 on daily subcutaneous elamipretide 0.5 mg/kg and oral heart failure medications...Our case suggests that elamipretide may have contributed to the improvement of LV function in this BTHS infant, supporting elamipretide's early use in BTHS. Our findings align with the previous studies in which elamipretide treatment demonstrated normalization of mitochondrial function and improvement in LV function."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Metabolic Disorders

Expanded-access use of elamipretide in a critically ill patient with Barth syndrome. (PubMed, Genet Med Open) - No abstract available

Journal • Cardiomyopathy • Cardiovascular

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. (PubMed, Ophthalmol Sci) - P2 | "Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period...The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Journal • P2 data • Age-related Macular Degeneration • Dermatology • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Pain • Pruritus • Retinal Disorders

ELViS-FA: FRDA Investigator Initiated Study (IIS) With Elamipretide (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Children's Hospital of Philadelphia | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jul 2024

Metastases • Trial completion • Trial completion date • Ataxia • Friedreich ataxia • Movement Disorders

ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD) (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Stealth BioTherapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD) (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Stealth BioTherapeutics Inc.

New P3 trial • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Next-generation ocular topical SBT-272 demonstrates optimized retina tissue exposure: building upon elamipretide for treating dry AMD (ARVO 2024) - "Our in vivo results suggest that topical ocular SBT-272 has an advanced PK profile relative to SC elamipretide, with optimized delivery into retinal tissue resulting in increased retinal tissue concentrations while reducing systemic exposure. SBT-272 is a next-generation compound in development that follows the foundational studies and mechanism of action of SC elamipretide. Additional animal studies are ongoing, and the results will inform future development decisions."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Long-term Efficacy and Safety of Elamipretide in Patients with Barth Syndrome: 168-Week Open-label Extension Results of TAZPOWER. (PubMed, Genet Med) - "Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Fatigue • Metabolic Disorders • Myositis

Selecting quantitative endpoints in Barth syndrome, an ultra-rare multisystem disorder (SIMD 2024) - "In developing and actualizing clinical trial endpoints for Barth Syndrome we confronted many of the challenges faced by other ultra-rare diseases. We achieved significantly positive outcomes in our study population, but outside the predetermined placebo-controlled study period. In an ultra-rare disease, a repeat study may not be possible for the simple reason that there may not be additional patients eligible for a repeat confirmatory clinical trial."

Genetic Disorders • Rare Diseases

NuPower: Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD) (clinicaltrials.gov) - P3 | N=102 | Active, not recruiting | Sponsor: Stealth BioTherapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders • Myositis • DNA2 • MGME1

ELViS-FA: FRDA Investigator Initiated Study (IIS) With Elamipretide (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Children's Hospital of Philadelphia | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Jul 2024

Metastases • Trial completion date • Trial primary completion date • Ataxia • Friedreich ataxia • Movement Disorders

NuPower: Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD) (clinicaltrials.gov) - P3 | N=130 | Recruiting | Sponsor: Stealth BioTherapeutics Inc. | Trial completion date: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date • Metabolic Disorders • Myositis • MGME1

Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide. (PubMed, Future Cardiol) - "Elamipretide localizes to the inner mitochondrial membrane where it associates with CL, improving mitochondrial function, structure and bioenergetics, including ATP synthesis. Numerous preclinical and clinical studies in BTHS and other forms of HF have demonstrated that elamipretide improves left ventricular relaxation by ameliorating mitochondrial dysfunction, making it well suited for therapeutic use in adolescent and adult patients with BTHS."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hypertrophic Cardiomyopathy • Metabolic Disorders

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. (PubMed, Neurology) - P3 | "Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated."

Clinical • Journal • Fatigue • Genetic Disorders • Metabolic Disorders • Myositis

Quality of life in Barth syndrome. (PubMed, Ther Adv Rare Dis) - P2/3 | "A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects with Barth Syndrome (TAZPOWER). https://clinicaltrials.gov/ct2/show/NCT03098797.Registration Number: NCT03098797."

HEOR • Journal • Cardiomyopathy • Cardiovascular • Fatigue • Hematological Disorders • Musculoskeletal Pain • Myositis • Neutropenia • Pain • Pediatrics

Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data. (PubMed, Orphanet J Rare Dis) - "In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Fatigue • Genetic Disorders • Hematological Disorders • Myositis • Neutropenia

Elamipretide-Mediated Visual Function Improvements Are Associated With Ellipsoid Zone Integrity in Patients With Geographic Atrophy (ARVO 2023) - "Purpose To perform a quantitative assessment of the effect of subcutaneous elamipretide (ELAM) on the ellipsoid zone (EZ) integrity and its relationship with visual function in patients with dry age-related macular degeneration (AMD) and geographic atrophy (GA)...The health of the ellipsoid zone layer could be a useful predictor of disease progression and aid in the selection of potential candidates for an eventual treatment with elamipretide. Elamipretide could potentially protect the photoreceptors in patients with age-related macular degeneration, slow disease progression, and improve vision."

Clinical • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

[PREPRINT] Elamipretide Improves ADP Sensitivity in Aged Mitochondria by Increasing Uptake through the Adenine Nucleotide Translocator (ANT) (bioRxiv) - “We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT.”

Preclinical • Preprint • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseases. (PubMed, JIMD Rep) - "In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years."

Journal • Metabolic Disorders • Myositis • Pediatrics