Million Arefayene

Final analysis of KOMET (NCT04924608), a phase 3 study of selumetinib in adults with NF1-PN.

Alice P. Chen, Maria Daniela D'Agostino, Yemima Berman, Angela Swampillai et autres

3110 Background: In 2025 the EMA and FDA expanded the approval of selumetinib (SELU; ARRY-142886, AZD6244) to adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). We report the final exploratory analysis of SELU efficacy and safety from the …

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First-in-Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of BIIB091, an Oral BTK Inhibitor, in Healthy Adult Participants

Hui-Hsin Tsai, Yi Gu, Katherine A. Riester, Sherman Chu et autres

Introduction: Multiple sclerosis (MS) affects 2.8 million people globally. Despite available disease-modifying therapies (DMTs), more effective treatments are needed to prevent/slow disability progression. BIIB091 is a selective, non-covalent oral Bruton’s tyrosine kinase (BTK) inhibitor. This Phase 1, first-in-human study evaluated safety, tolerability, …

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Pharmacokinetics and Safety of Selumetinib Granule Formulation in Children With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (SPRINKLE; phase I/II)

Pablo Hernáiz Driever, Uwe R. Kordes, Ines B. Brecht, Veronica Saletti et autres

PURPOSE Neurofibromatosis type 1 (NF1)–associated plexiform neurofibroma (PN) can substantially affect quality of life. The capsule and granule formulations of selumetinib (ARRY-142886, AZD6244) are approved for pediatric patients with symptomatic, inoperable NF1-PN (age ≥1 to 3 years, region dependent). SPRINKLE (ClinicalTrials.gov identifier: …

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A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1‐Related Plexiform Neurofibromas and Healthy Volunteers

Peiying Zuo, Million Arefayene, Wei‐Jian Pan, Tomoko Freshwater et autres

Abstract Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. …

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PRAX-562-102: A Phase 1 Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PRAX-562 in Healthy Volunteers (P4-9.011)

Rajeshwari Mahalingam, Michael Oldham, Corey B. Puryear, Prashant N. Bansal et autres

Objective: We report findings from a Phase 1 clinical trial characterizing the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PRAX-562 in healthy adults. Background: PRAX-562 is a next-generation sodium channel blocker with a unique profile expected to translate to a wider …

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Randomized Phase IIa Clinical Study of an Anti-αvβ6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis

Ganesh Raghu, Majd Mouded, Antje Prasse, Christopher C. Stebbins et autres

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A Phase IIb Randomized Clinical Study of an Anti-αvβ6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis

Ganesh Raghu, Majd Mouded, Daniel Charles Chambers, Fernando J. Martínez et autres

Abstract Rationale Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives To evaluate the efficacy and safety of BG00011, an anti-αvβ6 IgG1 monoclonal antibody, in the treatment of patients with IPF. Methods In a phase IIb randomized, double-blind, placebo-controlled trial, patients …

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Next‐generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells

Eris Bame, Hao Tang, Jeremy Carlos Burns, Million Arefayene et autres

Abstract Objectives Bruton's tyrosine kinase (BTK) plays a non‐redundant signaling role downstream of the B‐cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and …

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Discovery of BIIB068: A Selective, Potent, Reversible Bruton’s Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases

Bin Ma, Tonika Bohnert, Kevin L. Otipoby, Eric S. Tien et autres

Abstract Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these antibodies bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes and NETosis by neutrophils. Bruton’s …

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Evaluation of HRCT-Derived Quantitative Lung Fibrosis (QLF) Scores in an 8-Week Phase 2a Study for Treatment of Idiopathic Pulmonary Fibrosis (IPF) Using BG00011

JONATHAN G GOLDIN, Priya J. Bansal, R. Raj, Million Arefayene et autres

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Phase 2B dose selection of BG00011 for the treatment of idiopathic pulmonary fibrosis (IPF)

Million Arefayene, Majd Mouded, Chris Stebbins, Guolin Zhao et autres

Introduction: avb6 is upregulated on alveolar epithelial cells in IPF patients and drives the activation of TGF-b. BG00011 is an anti-αvβ6 monoclonal antibody. The BG00011 phase 2A, conducted in patients with IPF, demonstrated TGF-b suppression as evidenced by reduction in pSMAD2 signaling …

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Assessment of Drug Metabolism Enzyme and Transporter Pharmacogenetics in Drug Discovery and Early Development: Perspectives of the I-Pwg

William Rea Brian, Larry M. Tremaine, Million Arefayene, Ruben de Kanter et autres

Genetic variants of drug metabolism enzymes and transporters can result in high pharmacokinetic and pharmacodynamic variability, unwanted characteristics of efficacious and safe drugs. Ideally, the contributions of these enzymes and transporters to drug disposition can be predicted from in vitro experiments and …

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