Ocuvia (elamipretide) / Stealth BioTherapeutics - LARVOL DELTA

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

Stealth BioTherapeutics Announces PDUFA Action Date Extension for Elamipretide to Treat Patients with Barth Syndrome (PRNewswire) - "Stealth BioTherapeutics Inc...today announced that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for elamipretide, a first-in-class mitochondria-targeted therapeutic in development for individuals with Barth syndrome. The new PDUFA target action date is April 29, 2025. Stealth was notified last week that the Agency requires additional time to conduct a full review of supplemental information provided in response to recent FDA requests that were received following the positive Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting on October 10, 2024. The FDA advised that these submissions constitute Major Amendments to the NDA, resulting in a standard three-month extension from the original action date of January 29, 2025."

PDUFA • Genetic Disorders

Expanded-Access Use of Elamipretide Improves Quality of Life in Patients With Rare Mitochondrial Disorders Characterized by Ophthalmic Symptoms: A Case Series. (PubMed, Clin Case Rep) - "This case series presents the use of elamipretide in two patients with different progressive mitochondrial disorders (chronic progressive external ophthalmoplegia [CPEO] plus and neuropathy, ataxia, and retinitis pigmentosa [NARP] syndrome) characterized by ophthalmic traits. Elamipretide was well tolerated and both patients demonstrated improvement in symptoms while on therapy."

HEOR • Journal • Ataxia • Genetic Disorders • Inherited Retinal Dystrophy • Metabolic Disorders • Movement Disorders • Ocular Inflammation • Ophthalmology • Pain • Retinal Disorders • Retinitis Pigmentosa

FDA Advisory Committee meeting today on elamipretide in Barth Syndrome. Informative meeting for those interested in rare diseases. https://lnkd.in/gCWVP8NH (LinkedIn)

Elamipretide is getting a review and an advisory committee #CardioTwitter

Biosecurity Insights from the United States Swine Health Improvement Plan: Analyzing Data to Enhance Industry Practices. (PubMed, Animals (Basel)) - "With 12,195 sites surveyed across 31 states, the study provides a comprehensive snapshot of current biosecurity practices...The data also reflect the industry's response to the threat of FADs, exemplified by the implementation of the US SHIP in 2020. As the US SHIP program advances, these insights will guide industry stakeholders in refining biosecurity practices, fostering endemic re-emerging and FAD preparedness, and ensuring the sustainability of the swine industry in the face of evolving challenges."

Journal

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects With Leber's Hereditary Optic Neuropathy: A Randomized Trial. (PubMed, Ophthalmology) - "Elamipretide treatment was generally well tolerated with no serious adverse events reported. Although this study did not meet its primary BCVA efficacy endpoint, improvements across assessments on visual function during the OLE, and the post-hoc findings of the HVF central region, were encouraging and require further exploration."

Journal • Achromatopsia • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Stealth BioTherapeutics Announces Positive End-of-Phase 2 Meeting with FDA on the Development of Elamipretide in Patients with Dry Age-related Macular Degeneration (PRNewswire) - "Stealth BioTherapeutics...announced the successful and favorable outcomes of an end-of-phase 2 meeting with the U.S. Food and Drug Administration (FDA) for elamipretide, its lead drug candidate for the treatment of dry age-related macular degeneration (AMD)....The analyses demonstrated that patients with a greater degree of ellipsoid zone (EZ) integrity showed a better functional response in elamipretide-treated patients. These findings support that EZ attenuation is likely to predict disease progression and suggest clinical and functional benefit of elamipretide in dry AMD. Following the meeting, the FDA's minutes confirmed EZ attenuation as an approvable endpoint in dry AMD."

FDA event • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology

Subcutaneous Elamipretide for non-central geographic atrophy: Findings from the ReCLAIM study (EURETINA 2021) - "Subcutaneous elamipretide appeared safe in the ReCLAIM-1 trial. BCVA and LLVA in NCGA patients improved significantly at 24 weeks. Mean NCGA growth at 24 weeks appeared reduced compared to natural history studies, and further investigation is ongoing in the ReCLAIM-2 study."

Stealth BioTherapeutics to Showcase Leadership in Retinal Mitochondrial Health with Clinical Updates at Ophthalmic Conferences (BioSpace) - "Stealth Biotherapeutics Corp...announced today that multiple abstracts have been accepted for presentation at several leading ophthalmic conferences this fall. These abstracts feature novel clinical findings from the positive ReCLAIM trial, which evaluated elamipretide in patients with dry age-related macular degeneration (AMD), as well as clinical updates from the ongoing ReCLAIM-2 study in patients with extrafoveal, or non-central, geographic atrophy (GA) due to dry AMD....Subcutaneous Elamipretide for non-central geographic atrophy: Findings from the ReCLAIM study...David Boyer, M.D."

Therapies on the Horizon for Nonexudative AMD (Retina Today) - "Two C3 inhibitors, NGM621 (NGM Biopharmaceuticals) and pegcetacoplan (Apellis Pharmaceuticals), and one C5 inhibitor, avacincaptad pegol (Zimura, Iveric Bio), are showing promise as potential treatments to reduce the progression of geographic atrophy. Elamipretide (Stealth Biotherapeutics) binds to cardiolipin to stabilize mitochondrial structure and reduce the emission of reactive oxygen species, thereby potentially slowing and reversing the effects of oxidative stress. A recombinant AAV2-based investigational gene therapy, GT005 (Gyroscope Therapeutics), is designed to induce the expression of complement factor I."

Online posting

The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. (PubMed, J Biol Chem) - "As a proof of concept, we show that SS-31 alters divalent cation (calcium) distribution within the interfacial region and reduces the energetic burden of calcium stress in mitochondria. The mechanistic details of SS-31 revealed in this study will help inform the development of future compound variants with enhanced efficacy and bioavailability."

Journal • Metabolic Disorders

Recurrent Non-severe Hypoglycemia Aggravates Cognitive Decline in Diabetes and Induces Mitochondrial Dysfunction in Cultured Astrocytes. (PubMed, Mol Cell Endocrinol) - "SS-31 mediated protection of mitochondrial functions reversed RLG-induced cell viability defects and neurotrophin production. These findings demonstrate that RH induced astrocyte overactivation and mitochondrial dysfunction, leading to astrocyte-derived neurotrophin disturbance, which might contribute to diabetic cognitive decline. Targeting astrocyte mitochondria might represent a neuroprotective therapy for hypoglycemia-associated neurodegeneration in diabetes."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Severe Hypoglycemia • BDNF

Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease. (PubMed, J Biol Chem) - "MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling."

Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020. (PubMed, Asia Pac J Ophthalmol (Phila)) - "Six upcoming agents have shown results at least in the 2A phase. This includes intravitreal agents that are inhibitors of integrin (Risuteganib), intravitreal agents that disrupt the complement pathway (Zimura, APL-2), neuroprotective implants (Brimonidine DDS), a subcutaneous injectable (Elamipretide), and photobiomodulation (Valeda Light Delivery System)."

Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ophthalmology • Retinal Disorders

Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy. (PubMed, Int J Mol Sci) - "This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR...This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR."

Journal • Preclinical • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus

ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: Stealth BioTherapeutics Inc.; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Trial primary completion date • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

"$MITO Stealth BioTherapeutics Granted Pre-NDA Meeting For Elamipretide As A Treatment For Cardiomyopathy In Barth Syndrome https://t.co/zCXlI6ouqs" (@stock_titan)

NDA • Cardiomyopathy • Cardiovascular

An Intermediate Size Expanded Access Protocol of Elamipretide (clinicaltrials.gov) - P; N=N/A; Available; Sponsor: Stealth BioTherapeutics Inc.

Clinical • New trial • Metabolic Disorders • Rare Diseases

Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte. (PubMed, Elife) - "Most importantly, the tetra-peptide SS-31 prevents age-related excess proton entry, decreases the mitochondrial flash activity and mitochondrial permeability transition pore opening, rejuvenates mitochondrial function by direct association with ANT1 and the mitochondrial ATP synthasome, and leads to substantial reversal of diastolic dysfunction. Our results uncover the excessive proton leak as a novel mechanism of age-related cardiac dysfunction and elucidate how SS-31 can reverse this clinically important complication of cardiac aging."

Journal • Cardiovascular

Protective effects of SS-31 against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression. (PubMed, Am J Transl Res) - "And treating with SS-31 could significantly retard SCBT progression by rescuing the mitochondrial dysfunction-induced EndMT. Altogether, these results show that SDHB suppression-mitochondrial dysfunction-EndMT axis is a critical part of the CBT sclerosis and progression, while mitochondria-targeted drug SS-31 exerts an inhibitive effect on the above-mentioned axis, which opens new strategies to prevent and treat malignancies of CBT."

Journal • Metabolic Disorders • Oncology

Update on Elamipretide for the Treatment of AMD (Bascom Palmer Eye Institute)

CME

Hypertension exacerbates cerebrovascular oxidative stress induced by mild traumatic brain injury: protective effects of the mitochondria-targeted antioxidative peptide SS-31. (PubMed, J Neurotrauma) - "Persistent mTBI-induced oxidative stress in MCAs of SHRs was significantly decreased by inhibiting vascular NADPH oxidase (apocyinin). We propose, that hypertension- and mTBI-induced cerebrovascular oxidative stress likely lead to persistent dysregulation of CBF and cognitive dysfunction, which might be reversed by SS-31 treatment."

Journal • CNS Disorders • Cognitive Disorders • Hypertension • Mood Disorders • Vascular Neurology

Stealth BioTherapeutics Announces Development Financing To Advance Elamipretide Clinical Trials (PRNewswire) - "Stealth BioTherapeutics Corp...today announced the first closing under a Development Funding Agreement to support the clinical development of elamipretide....Stealth received $20 million.... Additional investors may participate in subsequent closings of up to an additional $35 million of near-term funding commitments....Stealth may receive up to an additional $35 million upon meeting certain pre-defined future milestones and subject to the agreement of the parties....Under the terms of the agreement, Stealth will pay participating investors regulatory approval milestone payments in annual increments on a pre-determined payment schedule over seven years....Stealth will retain exclusive worldwide commercial rights to elamipretide in all indications."

Financing • Friedreich ataxia

[VIRTUAL] Long-Term Mitochondrial Protection Reduces Proteinuria in Obese Aged Mice (KIDNEY WEEK 2020) - "Combined with improved ACR our results suggest that podocyte integrity, if not number, may be preserved in mice fed a Western diet by SS-31 intervention and that long-term mitochondrial protection is a potential therapeutic target to preserve renal function with age. Funding: Other NIH Support"

Genetic Disorders • Glomerulonephritis • Metabolic Disorders • Nephrology • Obesity • Renal Disease