Vincerinone (vatiquinone) / PTC Therap - LARVOL DELTA

Key Clinical and Regulatory Updates (PTC Therapeutics Press Release) - "Additional Sephience marketing authorization reviews ongoing including in Japan where decision is expected in Q4 2025; FDA meeting for votoplam Huntington's disease program planned for Q4; FDA meeting planned for vatiquinone Friedreich's ataxia program in Q4; Translarna NDA remains under FDA review."

FDA event • Japan filing • Duchenne Muscular Dystrophy • Friedreich ataxia • Huntington's Disease • Phenylketonuria

Long-Term Effectiveness and Tolerability of Vatiquinone in an Adult Friedreich's Ataxia Population (MDS Congress 2025) - P2 | "Long-term analyses demonstrate that vatiquinone treatment resulted in a significant slowing of disease progression in ambulatory and nonambulatory adults relative to natural history, supporting preserved function after long-term vatiquinone use."

Clinical • Ataxia • CNS Disorders • Movement Disorders

Vatiquinone Prevents Ferroptosis in Preclinical Models of Friedreich's Ataxia (MDS Congress 2025) - "These data confirm that vatiquinone has profound inhibitory effects on ferroptotic pathways in in vivo and in vitro preclinical models, protecting against underlying pathologies of FRDA, including accumulation of HETEs and GSH depletion."

Late-breaking abstract • Preclinical • Ataxia • CNS Disorders • Movement Disorders • GPX4

REPURPOSING MITOCHONDRIA PROTECTIVE TARGETS FOR ADJUVANT THERAPY IN INFLAMMATORY BOWEL DISEASES (UEGW 2025) - "Aims & Cellular toxicity of the drugs Acipimox, AICAR, ALCAR, Bezafibrate, Epi-743, Idebenone, Metformin, SS-31 and TUDCA was assessed in the intestinal epithelial cell line Mode-K and murine wild-type (WT) small intestinal (SI) organoids. Selected drugs targeting mitochondrial functions restored seeding efficiency, differentiation, and stemness of intestinal organoids from inflamed tissue sections of TNFΔARE mice, TNFΔARE pigs, and CD patients. These findings clearly support the potential of metabolic drug repurposing for adjuvant IBD therapy and indicate putative risks for Metformin."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • IL10

Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich's Ataxia. (PubMed, Pharmaceuticals (Basel)) - " A two-compartment model effectively described the pharmacokinetic profiles of vatiquinone after oral administration. Covariates significantly impacted exposures, including body weight, meals, disease status, comedications and body mass index."

Journal • PK/PD data • Ataxia • Friedreich ataxia • Inflammation • Movement Disorders

Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule. (PubMed, Biopharm Drug Dispos) - "The mean Day 6 accumulation ratio (ARAUC) suggested an accumulation ratio of 1.61 and 1.73 for 200 and 400 mg, respectively. The results of both studies support the recommendation of administering vatiquinone TID with fatty meals taken on a convenient dosing regimen."

Journal • Ataxia • Friedreich ataxia • Movement Disorders • Rare Diseases

Mitochondrial Diseases: Molecular Pathogenesis and Therapeutic Advances. (PubMed, MedComm (2020)) - "In parallel, metabolic modulators (e.g., coenzyme Q10, idebenone, EPI-743) aim to restore bioenergetics, and mitochondrial replacement technologies and transplantation are being explored. Addressing these issues through multidisciplinary research and clinical translation holds promise for transforming mitochondrial disease management and improving patient outcomes. By bridging the understanding of mitochondrial dysfunction with advanced therapeutic interventions, this review aims to shed light on effective solutions for managing these complex disorders."

Journal • Review • Gene Therapies • Genetic Disorders • Metabolic Disorders • Transplantation

EAP: Vatiquinone Expanded Access Protocol (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Medical University of South Carolina

New trial • Metabolic Disorders

A Safety Study for Previously Treated Vatiquinone (PTC743) Participants With Inherited Mitochondrial Disease (clinicaltrials.gov) - P3 | N=102 | Completed | Sponsor: PTC Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Metabolic Disorders

PTC Therapeutics Receives Complete Response Letter for Vatiquinone NDA (PRNewswire) - "The FDA stated in the CRL that substantial evidence of efficacy was not demonstrated for vatiquinone and that an additional adequate and well-controlled study would be needed to support NDA resubmission."

CRL • Friedreich ataxia

Key Clinical and Regulatory Milestones (PRNewswire) - "NDA reviews for vatiquinone (Friedreich's ataxia) and Translarna (nonsense mutation DMD) are ongoing, with regulatory action date of August 19, 2025 for vatiquinone...In May 2025, reported positive Phase 2 PIVOT-HD study results for votoplam (PTC518) in Huntington's Disease patients. PTC continues to collaborate with Novartis on next steps and aims to meet with FDA in Q4 2025 to discuss Phase 3 clinical trial design and potential accelerated approval pathway."

Clinical protocol • New P3 trial • PDUFA • Duchenne Muscular Dystrophy • Friedreich ataxia • Huntington's Disease

A Safety Study for Previously Treated Vatiquinone (PTC743) Participants With Inherited Mitochondrial Disease (clinicaltrials.gov) - P3 | N=102 | Active, not recruiting | Sponsor: PTC Therapeutics | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Metabolic Disorders

Therapeutic Approach to Epilepsy in Patients with Mitochondrial Diseases. (PubMed, Yonsei Med J) - "Emerging treatments include gene therapy, mitochondrial transplantation, and antioxidants such as EPI-743, which protect mitochondrial integrity and improve neurological function. Additionally, therapies that promote mitochondrial biogenesis, such as bezafibrate and epicatechin, are being explored for their potential to enhance mitochondrial proliferation and energy production...Patient-derived induced pluripotent stem cells can model specific mitochondrial dysfunctions in vitro, allowing for the testing of various treatments tailored to individual genetic and biochemical profiles. The future of mitochondrial medicine is promising, with the development of more targeted and personalized therapeutic strategies offering hope for improved management and prognosis of mitochondrial epilepsy."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Metabolic Disorders • Transplantation

PTC Therapeutics Announces FDA Acceptance and Priority Review for Vatiquinone NDA for the Treatment of Children and Adults with Friedreich's Ataxia (PRNewswire) - "PTC Therapeutics, Inc...announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for vatiquinone for the treatment of children and adults living with Friedreich's ataxia (FA). The application has been granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of Aug. 19, 2025...The vatiquinone NDA is based on data from the placebo-controlled MOVE-FA study as well as results from two long-term studies including pediatric and adult FA patients."

FDA filing • PDUFA • Priority review • Friedreich ataxia

Evaluating the efficacy of vatiquinone in preclinical models of Leigh syndrome and GPX4 deficiency. (PubMed, Orphanet J Rare Dis) - "Vatiquinone prevents ferroptosis, but fails to attenuate cell death induced by paraquat or rotenone and provided no significant benefit to survival in two mouse models of disease. Vatiquinone may prevent seizures in the Ndufs4(-/-) model. Our findings are consistent with recent press statements regarding clinical trial results and have implications for drug trial design and reporting in patients with rare diseases."

Journal • Preclinical • CNS Disorders • Epilepsy • Metabolic Disorders • Pediatrics • Rare Diseases • GPX4

A Study to Assess the Safety and Efficacy of Vatiquinone in Participants With Friedreich Ataxia (clinicaltrials.gov) - P3 | N=130 | Active, not recruiting | Sponsor: PTC Therapeutics | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Ataxia • Friedreich ataxia • Movement Disorders

PTC Therapeutics Announces Vatiquinone NDA Submission to FDA for the Treatment of Children and Adults Living with Friedreich Ataxia (PRNewswire) - "PTC Therapeutics, Inc...announced today the submission of the vatiquinone New Drug Application (NDA) for the treatment of children and adults living with Friedreich ataxia (FA) to the U.S. Food and Drug Administration (FDA)...The vatiquinone NDA is based on data from the placebo-controlled MOVE-FA study as well as results from two long-term studies including pediatric and adult FA patients...The vatiquinone NDA is the fourth approval application PTC has submitted to the FDA this year."

FDA filing • CNS Disorders • Friedreich ataxia

Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial (ICAR-Ataxia 2024) - No abstract available

Clinical • P3 data • Ataxia • Friedreich ataxia • Movement Disorders

Lack of Concentration-QTc Relationship and Cardiac Risk With Vatiquinone Therapeutic and Supratherapeutic Doses. (PubMed, Clin Pharmacol Drug Dev) - "No new safety signals were found, as safety data are consistent with the known safety profile of vatiquinone. These findings altogether demonstrated that there is a minimal cardiac risk for vatiquinone concentrations up to the supratherapeutic dose level."

Clinical • Journal • Ataxia • Friedreich ataxia • Movement Disorders • Rare Diseases

A Study of Vatiquinone for the Treatment of Participants With Friedreich Ataxia (clinicaltrials.gov) - P2 | N=5 | Completed | Sponsor: PTC Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Ataxia • Friedreich ataxia • Movement Disorders • FXN

Evaluating Pharmacological Interventions for Friedreich Ataxia: A Network Meta-Analysis of Randomised Trials (MDS Congress 2024) - "EPI-743 400mg and Deferiprone 40mg/kg/day demonstrated a poor response with MD of 13.06 (95% CI: 4.09; 22.04, p = 0.03) and 7.00 (95% CI: 2.63; 11.37, p = 0.12) respectively. Our preliminary analysis shows RT001 9g/day, A0001 750mg, and Idebenone variations yield significant improvements in FA patients. Forest Plot"

Retrospective data • Ataxia • CNS Disorders

Improvement in Upright Stability subscale of mFARS with Vatiquinone Treatment in MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial (MDS Congress 2024) - P2/3 | "Vatiquinone treatment resulted in clinically meaningful and statistically significant treatment effects on the USS, a sensitive and predictive endpoint for risk of loss of ambulation, prevention of which is a key goal for therapy in ambulatory FA patients. Previously presented at Muscular Dystrophy Association (MDA) on March 3, 2024."

Clinical • P3 data • Ataxia • CNS Disorders

Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial (MDS Congress 2024) - P2/3 | "MOVE-FA demonstrated clinically relevant benefits across the primary, secondary, and exploratory endpoints. Vatiquinone treatment resulted in a clinically meaningful and statistically significant treatment effect on the USS, a sensitive and predictive endpoint for risk of loss of ambulation, prevention of which is a key goal for therapy in ambulatory FA patients. Previously presented at Muscular Dystrophy Association (MDA) on March 6, 2024."

Clinical • P3 data • Ataxia • CNS Disorders

Determination of Vatiquinone Drug-Drug Interactions, as CYP450 Perpetrator and Victim, Using Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation. (PubMed, J Clin Pharmacol) - "As a perpetrator, the model predicted no risk for vatiquinone to significantly alter the drug exposures of CYP3A4 and CYP1A2 substrates as evident bynegligible reduction in both midazolam and caffeine area under the curve (AUC)inf and Cmax...With fluconazole coadministration, vatiquinone AUCinf and Cmax increased by nearly 50% and 25%, respectively. With efavirenz coadministration, vatiquinone AUCinf and Cmax decreased by approximately 20% and 10%, respectively. Results suggested that vatiquinone does not significantly impact CYP3A4 and CYP1A2 substrates and that moderate CYP3A4 inhibitors and inducers weakly impact vatiquinone AUC."

Journal • PK/PD data • Ataxia • Friedreich ataxia • Movement Disorders • Rare Diseases • CYP1A2

MIT-E: A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy (clinicaltrials.gov) - P2/3 | N=68 | Terminated | Sponsor: PTC Therapeutics | Completed ➔ Terminated; Sponsor decision.

Trial termination • CNS Disorders • Epilepsy • Metabolic Disorders