Qizenday (biotin) / MedDay - LARVOL DELTA

Diurnal Step Count Patterns in Progressive Multiple Sclerosis (AAN 2023) - "Design/Methods Participants (n=577) in the SPI2 study of MD1003 (high dose biotin) in progressive MS underwent EDSS and T25FW every three months with up to 27 months of follow up...Conclusions The association between lower physical activity and disability metrics is not uniform throughout the day, and changes with the seasons. These results highlight the need for consistency in timing of clinical evaluation in research, and provide important insight into specific times of day that may be preferable for effective rehabilitation interventions."

CNS Disorders • Multiple Sclerosis

High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo. (PubMed, Int J Mol Sci) - "The histological analysis of the grafted animals shows that MD1003 increased proliferation and accelerates differentiation of human oligodendroglia, but without enhancing their myelination potential. These findings provide important insights into the role of MD1003 on murine and human oligodendrocyte maturation/myelination that may explain the mitigated outcome of ALS/MS clinical trials."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Multiple Sclerosis • Solid Tumor

BIOSEP: Study to Assess Effect and Safety of High Dose of Biotin (Qizenday®) in Progressive Multiple Sclerosis (clinicaltrials.gov) - P=N/A; N=103; Completed; Sponsor: Nantes University Hospital; Recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Multiple Sclerosis

High-dose biotin for multiple sclerosis: A systematic review and meta-analyses of randomized controlled trials. (PubMed, Mult Scler Relat Disord) - "A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken."

Clinical • Journal • Review • CNS Disorders • Multiple Sclerosis

Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003). (PubMed, Brain Behav) - "MD1003 treatment was associated with clinical, BV, and CSCV improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at multiple sclerosis onset, and a treatment response at M12 is consistent with a better effect in less disabled patients."

Biomarker • Clinical • Journal • CNS Disorders • Multiple Sclerosis • Plasma NfL

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet Neurol) - P3 | "This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis."

Clinical • Journal • P3 data • CNS Disorders • Multiple Sclerosis • Solid Tumor

Effect of MD1003 in Progressive Multiple Sclerosis (SPI2) (clinicaltrials.gov) - P3; N=642; Terminated; Sponsor: MedDay Pharmaceuticals SA; Trial completion date: Jun 2023 ➔ Apr 2020; Active, not recruiting ➔ Terminated; Sponsor decision for business purposes

Clinical • Trial completion date • Trial termination • CNS Disorders • Multiple Sclerosis

SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study (clinicaltrials.gov) - P2; N=15; Completed; Sponsor: MedDay Pharmaceuticals SA; Recruiting ➔ Completed; Phase classification: P1/2 ➔ P2

Clinical • Phase classification • Trial completion • Genetic Disorders • Pain

Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Completed; Sponsor: MedDay Pharmaceuticals SA; Active, not recruiting ➔ Completed

Clinical • Trial completion

Effects of Biotin on survival, ensheathment, and ATP production by oligodendrocyte lineage cells in vitro. (PubMed, PLoS One) - "Here, we investigate the effects of high dose Biotin (MD1003) on the functional properties of post-natal rat derived oligodendrocyte progenitor cells (OPCs)...For most assays, the positive effects of Biotin were observed at the higher end of the dose-response analysis. We conclude that Biotin, in vitro, protects OL lineage cells from metabolic injury, enhances myelin-like ensheathment, and is associated with increased ATP production."

Journal • CNS Disorders • Multiple Sclerosis • Solid Tumor

High-dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy. (PubMed, Brain Pathol) - "Recently, high-dose pharmaceutical-grade biotin (MD1003) was shown to improve clinical parameters in a subset of patients with chronic progressive multiple sclerosis...High-dose biotin normalized the hyperactivation of mTORC1, thus restoring lipid homeostasis. These results shed light into the mechanism of action of high-dose biotin of relevance for neurodegenerative and metabolic disorders.."

Journal • CNS Disorders • Gene Therapies • Metabolic Disorders • Multiple Sclerosis • Pain

[VIRTUAL] Efficacy and safety results of the phase 3 SPI2 study of MD1003 (high dose Pharmaceutical grade Biotin) in progressive MS (EAN 2020) - P3 | "Efficacy and safety results of the phase 3 SPI2 study of MD1003 in progressive MS will be presented."

Clinical • P3 data • CNS Disorders • Multiple Sclerosis

Remotely Monitored Ambulatory Activity Correlates with Disability in Progressive MS: A Baseline Analysis from the SPI2 Phase 3 Clinical Trial of MD1003 (High Dose Pharmaceutical Grade Biotin) (AAN 2020) - "STEPS correlated with clinical measures, cognitive function, volumetric MRI measures, and quality of life at baseline in SPI2. Remote monitoring of ambulation (Fitbit) may be a surrogate for MS disability in clinical trials."

Clinical • P3 data • MRI

Results of the Phase 3 SPI2 Study of MD1003 (high dose Pharmaceutical grade Biotin) in Progressive MS (AAN 2020) - P3 | "Results of the phase 3 SPI2 study of MD1003 in this progressive MS population will be presented."

P3 data

Treatment of progressive MS with MD1003 (high dose pharmaceutical grade biotin): real-world evidence (ECTRIMS 2018) - "MD1003 300mg/day was effective in the treatment of PMS in a real-world clinical setting; at 1 year of treatment, 23% of pts experienced improvement in MS-related disease activity (as measured by EDSS or TW25). MD1003 was also well-tolerated. This real-world study supports the growing body of evidence that MD 1003 is an effective and safe treatment for PMS."

Clinical • HEOR • Real-World Evidence • Biosimilar • CNS Disorders • Multiple Sclerosis

MD1003 (High Dose Pharmaceutical Grade Biotin; hdPB) for the Treatment of Progressive Multiple Sclerosis: Baseline Data and Results From an Early Access Program (AAN 2018) - "In this large cohort of patients, the efficacy and safety of MD1003 are consistent with those of the MS-SPI trial results in a database of over 5,000 French patients with PMS."

CNS Disorders • Multiple Sclerosis

RI Study to Assess and Compare the Pharmacokinetic Parameters of MD1003 in Renal Impaired Patients and Healthy Subjects (clinicaltrials.gov) - P1; N=24; Terminated; Sponsor: MedDay Pharmaceuticals SA; N=36 ➔ 24; Trial completion date: Jul 2020 ➔ Mar 2020; Recruiting ➔ Terminated; Due to other phase 3 trial failure to meet primary endpoint

Clinical • Enrollment change • Trial completion date • Trial termination • Renal Disease

HI Study to Assess and Compare the Pharmacokinetic Parameters of MD1003 in Hepatic Impaired Patients and Healthy Subjects (clinicaltrials.gov) - P1; N=15; Terminated; Sponsor: MedDay Pharmaceuticals SA; Trial completion date: Jun 2020 ➔ Mar 2020; Recruiting ➔ Terminated; Due to other Phase 3 trial failure to meet primary endpoint

Clinical • Trial completion date • Trial termination

Spinal Cord Area Correlates with Disability and Quality of Life in Progressive MS: A Baseline MRI Analysis from the SPI2 Phase 3 Trial of MD1003 (high dose Pharmaceutical grade Biotin) (AAN 2020) - "This is the first successful deployment of cross-platform, PSIR spinal cord imaging in an MS randomized controlled trial. Total cord areas correlated with clinical disability (EDSS, T25FW) in progressive MS patients enrolled in SPI2. Total cord areas may serve as a correlate of clinical disability, either alone or with brain MRI metrics."

HEOR • P3 data • MRI

High-dose pharmaceutical grade biotin (MD1003) in amyotrophic lateral sclerosis: A pilot study. (PubMed, EClinicalMedicine) - P2; "Given the favourable safety profile of MD1003 and an imbalance between treatment groups favouring placebo, additional, larger studies in ALS are warranted. MedDay Pharmaceuticals."

Clinical • Journal

Spinal Cord Area Correlates With Disability And Quality Of Life In Progressive Ms: Baseline Mri Analysis From The Spi2 Ph3 Trial Of Md1003 (hdpb) (ACTRIMS Forum 2020) - "This is the first successful deployment of cross-platform, PSIR spinal cord imaging in a clinical trial in MS. Total cord areas (TCA) correlated with clinical measures of disability (EDSS, T25FW) in not active progressive MS patients enrolled in the phase 3 SPI2 study of MD1003 (hdPB). TCA may serve as a correlate of clinical disability, either alone or with traditional brain MRI metrics."

HEOR • MRI

Remotely Monitored Ambulatory Activity Correlates Withdisability In Progressive Ms: Baseline Data From The SPI2 Ph3 Trial Of Md1003 (hdpb Biotin) (ACTRIMS Forum 2020) - "STEPS correlate with clinical measures (EDSS, T25FW), cognitive function (SDMT), volumetric MRI measures (NBV, GMV and TCA), and quality of life (PHCS/MHCS-29) at baseline in the SPI2 study. Remote gait monitoring via Fitbit may be a general surrogate for MS disability in clinical trials."

MRI

Axonal Integrity by MRS at Baseline in the SPI2 Ph3 Trial of MD1003 (hdPB): Effect of Sex, Disease Burden, and Progressive MS Type (ACTRIMS Forum 2020) - "In this MRS-based substudy of the SPI2 phase 3 trial of MD1003 (hdPB), PPMS and SPMS patients appeared similar. A future analysis of longitudinal changes in neuronal integrity, as assessed by MRS, will be carried out at the conclusion of SPI2."

TQT2 Study to Evaluate the Effect of MD1003 on Cardiac Repolarization in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: MedDay Pharmaceuticals SA; Not yet recruiting ➔ Recruiting

Enrollment open

HI Study to Assess and Compare the Pharmacokinetic Parameters of MD1003 in Hepatic Impaired Patients and Healthy Subjects (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: MedDay Pharmaceuticals SA

Clinical • New P1 trial