BIIB091 / Biogen - LARVOL DELTA

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Completed | Sponsor: Biogen | Terminated ➔ Completed

Monotherapy • Trial completion • CNS Disorders • Inflammation • Multiple Sclerosis

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Terminated | Sponsor: Biogen | Trial completion date: Sep 2027 ➔ Feb 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2027 ➔ Feb 2026

Monotherapy • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Inflammation • Multiple Sclerosis

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting | N=275 ➔ 127

Enrollment change • Enrollment closed • Monotherapy • CNS Disorders • Inflammation • Multiple Sclerosis

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=275 | Recruiting | Sponsor: Biogen | Trial completion date: Nov 2026 ➔ Sep 2027 | Trial primary completion date: Jul 2025 ➔ Sep 2027

Monotherapy • Trial completion date • Trial primary completion date • CNS Disorders • Inflammation • Multiple Sclerosis

A Study to Find Out How Multiple Doses of BIIB091 Affect the Electrical Activity of the Heart in Healthy Participants (clinicaltrials.gov) - P1 | N=69 | Completed | Sponsor: Biogen | Recruiting ➔ Completed

Trial completion

A Study to Find Out How Different Forms of BIIB091 is Processed in The Body With and Without Food in Healthy Participants (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Biogen | Recruiting ➔ Completed

Trial completion

A Study to Find Out How Different Forms of BIIB091 is Processed in The Body With and Without Food in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Find Out How Different Forms of BIIB091 is Processed in The Body With and Without Food in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Biogen

New P1 trial

A Study to Find Out How Multiple Doses of BIIB091 Affect the Electrical Activity of the Heart in Healthy Participants (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Find Out How Multiple Doses of BIIB091 Affect the Electrical Activity of the Heart in Healthy Participants (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: Biogen

New P1 trial

Phase Appropriate Process Development and Scale-up of Selective BTK Inhibitor BIIB091 (ACS-Fall 2024) - "Phase appropriate process development enabled by chemical innovation was the key to design and implementation of more efficient synthesis processes that enabled successful BIIB091 Non-GMP and GMP drug substance campaigns. In this presentation we will discuss the process optimization that led to efficient synthesis of BIIB091, and innovative approaches to both starting material synthesis and API manufacturing will be discussed."

CNS Disorders • Multiple Sclerosis

Mass Balance: A Study to Look at How a Single Oral Dose of Carbon-14-Labelled [14C] BIIB091 Moves Through and is Processed by the Body in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion

Mass Balance: A Study to Look at How a Single Oral Dose of Carbon-14-Labelled [14C] BIIB091 Moves Through and is Processed by the Body in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed

Mass Balance: A Study to Look at How a Single Oral Dose of Carbon-14-Labelled [14C] BIIB091 Moves Through and is Processed by the Body in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

Mass Balance: A Study to Look at How a Single Oral Dose of Carbon-14-Labelled [14C] BIIB091 Moves Through and is Processed by the Body in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Biogen

New P1 trial

Design of the Phase 2 FUSION Trial of Reversible Non-covalent BTK Inhibitor BIIB091 in Participants with Relapsing Forms of Multiple Sclerosis (MSMilan 2023) - P2 | "Objectives/Aims: To present the design of FUSION Phase 2 trial protocol, a 2-part study to sequentially evaluate the safety and efficacy of BIIB091 monotherapy and BIIB091 combination therapy with diroximel fumarate (DRF) in participants with relapsing forms of MS (RMS). BIIB091 monotherapy and BIIB091 in combination with DRF are being investigated in the phase 2 FUSION study as a potential high-efficacy oral treatment for patients with RMS."

P2 data • CNS Disorders • Inflammation • Multiple Sclerosis

Optimization of formulation and treatment regimen of BIIB091, a non-covalent Bruton's tyrosine kinase inhibitor (MSMilan 2023) - "BIIB091 250 mg IR tablets twice daily with MF meals achieved PK/PD targets. This regimen was selected as one of the treatment regimens for phase 2 trial in patients with RMS."

CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis • CD69

A Study to Evaluate Safety and Efficacy of BIIB091 in Participants With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2 | N=275 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • CNS Disorders • Multiple Sclerosis

A Study to Evaluate Safety and Efficacy of BIIB091 in Participants With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2 | N=275 | Not yet recruiting | Sponsor: Biogen | Trial completion date: Jul 2026 ➔ Nov 2026 | Trial primary completion date: Jul 2026 ➔ Jul 2025

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Evaluate Safety and Efficacy of BIIB091 in Participants With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2 | N=275 | Not yet recruiting | Sponsor: Biogen

Combination therapy • Monotherapy • New P2 trial • CNS Disorders • Multiple Sclerosis

Study of BIIB091 Formulations in Healthy Participants (clinicaltrials.gov) - P1 | N=59 | Completed | Sponsor: Biogen | Recruiting ➔ Completed | Trial completion date: May 2022 ➔ Sep 2022 | Trial primary completion date: May 2022 ➔ Sep 2022

Trial completion • Trial completion date • Trial primary completion date

Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression? (PubMed, CNS Drugs) - "In this review, we discuss where and to what extent BTK is involved in the immunological and molecular cascades driving MS progression. We furthermore summarize all mechanistic, preclinical, and clinical data on the various BTK inhibitors (evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, orelabrutinib, BIIB091) that are currently in development for treatment of MS, with a particular focus on the potential ability of either drug to control MS progression."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor

Efficient Synthesis of BIIB091 Enabled by Chemical Innovations (ACS-Sp 2022) - "Chemical innovation was the key to design and implementation of more efficient process that enabled successful BIIB091 Non-GMP and GMP drug substance campaigns. In this presentation we will discuss the process optimization that led to efficient synthesis of BIIB091, and innovative approaches to both starting material synthesis and API manufacturing will be discussed."

CNS Disorders • Multiple Sclerosis

Study of BIIB091 Formulations in Healthy Participants (clinicaltrials.gov) - P1; N=52; Recruiting; Sponsor: Biogen; Trial completion date: Nov 2021 ➔ May 2022; Trial primary completion date: Nov 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date

Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis. (PubMed, J Med Chem) - "Herein, we describe the discovery of BIIB091, a structurally distinct orthosteric ATP competitive, reversible inhibitor that binds the BTK protein in a DFG-in confirmation designed to sequester Tyr-551, an important phosphorylation site on BTK, into an inactive conformation with excellent affinity. Preclinical studies demonstrated BIB091 to be a high potency molecule with good drug-like properties and a safety/tolerability profile suitable for clinical development as a highly selective, reversible BTKi for treating autoimmune diseases such as MS."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis