Catena (idebenone) / Santhera, Chiesi - LARVOL DELTA

Idebenone Accepted by FDA for Priority Review for Leber Hereditary Optic Neuropathy (LHON) (GlobeNewswire) - "The submission was based on the safety and efficacy data from Phase 3 (RHODOS) and Phase 4 (LEROS) studies....The target action date for the FDA decision is February 28, 2026."

FDA filing • PDUFA • Priority review • Leber Hereditary Optic Neuropathy

Impact of patient characteristics on time to symptom onset in pre-symptomatic eyes from the Case Record Survey-2 (SOE 2025) - P=N/A | "Analysis of pre-symptomatic eyes from CRS-2 suggests ΔOoS is not significantly impacted by age at OoS, extent of vision loss in the first eye or by mtDNA mutation. Caution must be taken in interpreting these results due to the small sample size."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Visual acuity outcomes by causative mutation in Leber Hereditary Optic Neuropathy: Analyses from LEROS and Case Record Survey-2 (ARVO 2025) - P=N/A, P4 | "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."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Individual disease trajectories by mutation in subacute/dynamic eyes from the Case Record Survey-2 (ARVO 2025) - P=N/A | "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."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Post-hoc Analysis of the LEROS Study: Impact of Time to Idebenone Initiation on Visual Acuity in Leber Hereditary Optic Neuropathy (AAN 2025) - P4 | "This post-hoc analysis of the LEROS study offers valuable insights into the impact of treatment initiation timing on VA, despite the small sample size and large variability of the data."

Retrospective data • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Sex-based Differences in Visual Acuity Outcomes in a Historical Cohort of Patients with Leber Hereditary Optic Neuropathy from Case Record Survey-2 (CRS-2) (AAN 2025) - P=N/A | "Objective:The Case Record Survey-2 (CRS-2; NCT02796274) was conducted to establish the natural history of LHON in idebenone-naïve patients...The clinical course of LHON may differ based on sex and age at symptom onset."

Clinical • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis

LEBER'S HEREDITARY OPTIC NEUROPATHY - THE CHALLENGE OF TREATMENT IN PAEDIATRIC PATIENTS - CASE REPORT (SSIEM 2024) - "In 2015, EMA approved idebenone (Raxone®), a synthetic CoQ10 analogue, for the treatment of LHON for vision recovery... We face many challenges, such as idebenone treatment, dosage, treatment duration and monitoring. Neurotransmitter and creatine related disorders"

Case report • Clinical • Astigmatism • Infectious Disease • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Pediatrics

Idebenone treatment for Leber hereditary optic neuropathy: Time to clinically relevant recovery in the LEROS study (EAN 2024) - P4 | "Longer duration of idebenone treatment (beyond 1 y) further improved visual outcomes regardless of LHON disease phase. This improvement was most pronounced for eyes with the m.14484T>C mutation."

Clinical • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term safety of idebenone in patients with Leber hereditary optic neuropathy: Results from the PAROS study (ARVO 2024) - P=N/A | "The safety profile reported here is similar to that observed in a previous open-label study (LEROS). Results from this long-term real world study therefore confirm that idebenone is well-tolerated in patients with LHON when used in routine clinical practise. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Assessing Clinically Relevant Recovery of Visual Acuity Over Time in Patients with Leber Hereditary Optic Neuropathy Treated with Idebenone: Results from the LEROS Study (AAN 2024) - P4 | "Regardless of LHON disease stage, the percentage of eyes with improved VA increased progressively over time during idebenone treatment."

Clinical • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis

Current and Future Landscape in Genetic Therapies for Leber Hereditary Optic Neuropathy. (PubMed, Cells) - "In 2015, an antioxidant idebenone (Raxone) received European marketing authorisation to treat visual impairment in patients with LHON, and since then it was introduced into clinical practice in several European countries. This manuscript discusses the phenotype and genotype of the LHON disease with complexities and peculiarities such as incomplete penetrance and gender bias, which have challenged the therapies in development emphasising the most recent use of gene therapy. Furthermore, we review the latest results of the three clinical trials based on adeno-associated viral (AAV) vector-mediated delivery of NADH dehydrogenase subunit 4 (ND4) with mitochondrial targeting sequence, highlighting the differences in the vector design and the rationale behind their use in the allotopic transfer."

Journal • Review • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy of idebenone in patients with LHON according to sex and disease phase: Results from the LEROS study (EAN 2023) - P4 | "Idebenone improved the ratio of positive to negative VA outcomes in a large proportion of patients with LHON. Treatment with idebenone significantly increased recovery in chronic female and male eyes and reduced the frequency of VA worsening in both sexes irrespective of disease phase."

Clinical • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy of idebenone in patients with LHON in the LEROS study: analyzing change in visual acuity categories according to causative mutation and disease phase (SOE 2023) - P4 | "Idebenone treatment promoted a transition toward improved functional VA categories in eyes with the m.G11778A and m.T14484C genotypes, particularly by reducing the proportion of off-chart eyes. Results in m.G3460A eyes were limited by an unexpectedly mild disease course in the NH cohort; further study of the impact of idebenone treatment in this subgroup is needed. _x000D_ _x000D_ _x000D_"

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy of idebenone in patients with LHON in the LEROS study: analyzing change in visual acuity over time according to age (SOE 2023) - P4 | "In eyes of patients ≥18 years, VA improvement at Month 24 was greater in idebenone-treated eyes versus those in the NH cohort. Treatment benefit was particularly apparent in the chronic phase, corresponding to >10 additional letters on the ETDRS chart. In chronic eyes from patients <18 years, a non-significant trend was observed in favor of idebenone; in subacute/dynamic eyes spontaneous VA recovery was unexpectedly high in the NH cohort."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy of idebenone in patients with LHON according to age at onset and disease phase: Results from the LEROS study (ARVO 2023) - P4 | "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."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing change in VA categories according to causative mutation and disease phase (ARVO 2023) - P4 | "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."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Santhera Concludes Agreement with French Authorities on Raxone Reimbursement and Plans to Submit a Request for an Early Access Program for Vamorolone (GlobeNewswire) - "Santhera Pharmaceuticals...announces that it has secured a final reimbursement agreement with the French authorities related to Raxone® (idebenone) for the treatment of Leber's hereditary optic neuropathy (LHON) and sales are expected to resume shortly....Santhera will make repayments in the total amount of approximately EUR 25 million, with 30% due around mid-2024 and the remainder one year later....The first payment is currently expected to be covered by sales generated until mid-2024, while the majority of the second payment will be covered by sales beyond mid-2025....Earlier in January, Santhera announced FDA acceptance of the new drug application (NDA) for vamorolone for DMD for filing. Subject to approval, Santhera plans to launch vamorolone in the U.S. in Q4-2023. European marketing authorization application (MAA) for vamorolone has been validated and is under review by the EMA which could pave the way for a first EU launch in late 2023."

European regulatory • Launch Europe • Launch US • NDA • Reimbursement • Duchenne Muscular Dystrophy

Molecular profiling of advanced pancreatic cancer (PC) patients from a phase I/II study using circulating tumor DNA. (ASCO 2017) - P2; " Plasma samples were banked from patients enrolled in the previously reported Phase Ib/II trial of gemcitabine with placebo or vismodegib (NCT01064622; Catenacci et al JCO 2015). ctDNA analysis of this cohort of banked PC plasma samples described the landscape of genomic aberrations at baseline and over time, including rare but potentially important actionable events including ERBB2 and FGFR2 amplifications and IDH1 mutation. We demonstrate a sensitive method for re-analysing trial outcomes, despite limiting plasma volume and time lapse since samples were collected."

Biomarker • P1/2 data • Retrospective data • Biosimilar • Pancreatic Cancer

Long-term clinical benefit of idebenone in LHON: Results from the prospective, natural history-controlled LEROS study (EAN 2022) - "In LEROS, long-term treatment with idebenone resulted in prolonged clinical benefit in patients with LHON. This benefit was largely driven by preventing significant VA loss in the subacute/dynamic phase, and by VA recovery in the chronic phase."

Clinical • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Long-term efficacy and safety of idebenone in patients with LHON in the chronic phase: Results from the LEROS study (ARVO 2022) - P4 | "LEROS provides evidence of a significant therapeutic benefit of idebenone treatment in patients with LHON in the chronic stage, a group for whom viable treatment options are otherwise severely limited."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Long-term efficacy and safety of idebenone in patients with LHON in the subacute/dynamic phase: Results from the LEROS study (ARVO 2022) - P4 | "LEROS corroborates the outcomes of previous studies, demonstrating that long-term treatment with idebenone results in prolonged clinical benefit in patients with LHON in the subacute/dynamic phase."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

PAROS: Post Authorisation Safety Study With Raxone in LHON Patients (clinicaltrials.gov) - P=N/A; N=229; Completed; Sponsor: Santhera Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

LEROS: Study to Assess the Efficacy and Safety of Raxone in LHON Patients (clinicaltrials.gov) - P4; N=199; Completed; Sponsor: Santhera Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Phase III Study With Idebenone in Patients With Duchenne Muscular Dystrophy (SIDEROS-E) (clinicaltrials.gov) - P3; N=161; Terminated; Sponsor: Santhera Pharmaceuticals; N=266 ➔ 161; Trial completion date: Jan 2024 ➔ Oct 2020; Recruiting ➔ Terminated; Trial primary completion date: Dec 2023 ➔ Oct 2020; Interim analysis concluded to futility of main study SIDEROS (SNT-III-012)

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

SIDEROS: A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids (clinicaltrials.gov) - P3; N=255; Terminated; Sponsor: Santhera Pharmaceuticals; Trial completion date: Aug 2021 ➔ Oct 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Aug 2021 ➔ Oct 2020; Interim analysis concluded to futility

Clinical • Trial completion date • Trial primary completion date • Trial termination • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy