Diagnosis of RMS [relapsing-remitting multiple sclerosis (RRMS) or active secondary progressive multiple sclerosis (SPMS)] in accordance with the 2017 Revised McDonald criteria.

Time since MS symptom onset is <20 years.

Must have expanded disability status scale (EDSS) score of 0 through 5.0 at screening and baseline.

Must have at least 1 of the following occurring prior to Baseline (Day 1):

≥2 clinical relapses in the last 24 months (but not within 30 days prior to Baseline [Day 1]) with at least 1 relapse during the last 12 months prior to randomization.

≥1 clinical relapse within the past 24 months (but not within 30 days prior to Baseline [Day 1]) and ≥1 new brain MRI lesion (Gd-positive and/or new or enlarging T2 hyperintense lesion) within the past 12 months prior to randomization. The screening MRI could be used to satisfy this criterion (if needed for inclusion, local reading is required). For new or enlarging T2 hyperintense lesions, the reference scan cannot be >12 months prior to randomization.

≥1 GdE lesion on brain MRI within 6 months prior to randomization.

Key

Diagnosis of primary progressive multiple sclerosis (PPMS) in accordance with the 2017 Revised McDonald criteria.

An MS relapse that has occurred within 30 days prior to Baseline (Day 1) or the participant has not stabilized from a previous relapse at the time of screening.

History of severe allergic, anaphylactic reactions or hypersensitivity reaction to BIIB091 or DRF, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study, including the following:

Known hypersensitivity to any components of the study treatment

Known hypersensitivity to previous fumarate or bruton's tyrosine kinase (BTK) inhibitor treatments

History of hypersensitivity to parenteral administration of Gd-based contrast agents

Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within the past 4 weeks prior to Baseline.

History or positive test result at screening for human immunodeficiency virus (HIV).

Current or history of hepatitis C infection regardless of viral load.

Current or possible hepatitis B.

Current enrollment or plan to enroll in any other drug, biological, device, clinical study, or treatment with an investigational drug or approved therapy for investigational use within 90 days prior to randomization or 5 half-lives of the drug or therapy, whichever is longer.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.