BIIB023 / Biogen - LARVOL DELTA

TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro. (PubMed, BMC Med) - "Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • CD68 • PTPRN • TARDBP • TNFSF12 • TNFSF13

BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis (clinicaltrials.gov) - P2; N=211; Recruiting; Sponsor: Biogen; Trial primary completion date: Sep 2016 ->Dec 2016

Trial primary completion date • Biosimilar • Lupus

TWEAK/fn14 pathway blockade attenuates renal disease in autoantibody-induced nephritis (ICA 2012) - Presentation time: 10.05.2012, 10:30-12:30; Fn14KO mice had significantly decreased levels of proteinuria as compared to Fn14 WT mice (day 7: 61+24 vs 220+42 mg/dl, p<0.01; day 14: 99+50 vs. 678+205 mg/dl, p=0.02; day 21: 101+49 vs 678+205 mg/dl, p=0.02); Moreover, crescent formation and tubular dilatation were significantly decreased in Fn14KO mice, as were MCP-1, RANTES, and IP-10 kidney mRNA expression levels

Preclinical-animal • Lupus

Neuropsychiatric lupus, the blood brain barrier, and the TWEAK/Fn14 pathway (Front Immunol) - "This review summarizes the evidence implicating BBB damage as an important component in NPSLE development, occurring via damage to barrier integrity by environmental triggers such as infection and stress; cerebrovascular ischemia as result of a generally prothrombotic state; and immune mediated EC activation, mediated by antibodies and/or inflammatory cytokines. Additionally, new evidence supporting the role of TWEAK/Fn14 signaling in compromising the integrity of the BBB in lupus will be presented."

Review • Immunology • Lupus

A phase I, randomized, double-blind, placebo-controlled, single-dose, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of BIIB023 (Anti-TWEAK) in subjects with rheumatoid arthritis (ACR/ARHP 2011) - P1, Anti-TWEAK (NCT00771329); N=53; Single dose IV administration of BIIB023 demonstrated a favorable safety and tolerability profile with no dose-dependent safety finding observed in any of the dose groups; The PK profile of BIIB023 revealed a t1/2 of approximately 24 days in the high doses of 10 and 20mg/kg

P1 data • Rheumatoid Arthritis

Biogen third quarter 2015 revenues increase 11% to $2.8 billion; Company raises 2015 full year guidance (Businesswire) - "Biogen has ceased development of anti-TWEAK in lupus nephritis after a Phase 2 futility analysis. Biogen will provide more information on the anti-TWEAK program in future scientific presentations."

Discontinued • Immunology • Lupus

Analyst Day (Biogen) - P1 data release

P1 data • Rheumatoid Arthritis

Biogen Idec: Q4 '12 Results (Biogen) - Anticipated P2 POC data for lupus between 2013 and 2016

Anticipated P2 data • Lupus

Safety, tolerability, pharmacokinetics, and pharmacodynamics of anti-TWEAK monoclonal antibody in patients with rheumatoid arthritis (Clin Ther) - P1, N=53; NCT00771329; Sponsor: Biogen Idec; PMID: 23928094; "The incidence of treatment-emergent adverse events for the BIIB023 monotherapy cohorts and open-label cohorts of BIIB023 as add-on therapy to TNF inhibitors compared with placebo were 47% and 50% versus 33%, respectively....Serum-soluble TWEAK levels were suppressed at all dose levels by 6 hours post-dose and recovered to baseline between days 7 and 28."

Biomarker • P1 data • Immunology • Rheumatoid Arthritis