otilimab (GSK3196165) / GSK, Novartis - LARVOL DELTA

Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X). (PubMed, BMJ Open) - P3 | "No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab."

Clinical • Journal • P3 data • Immunology • Infectious Disease • Inflammatory Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Tuberculosis • CSF2

Meaningful score changes for SF-36v2, FACIT-fatigue, and RASIQ in rheumatoid arthritis. (PubMed, J Patient Rep Outcomes) - "This study derived WPMI thresholds for SF-36v2, FACIT-Fatigue, and RASIQ among patients with RA, using multiple anchors. Derivation of WPMI thresholds for these PRO instruments will enable their broader use in evaluating and interpreting treatment benefit in future RA studies."

Journal • Fatigue • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatoid Arthritis • Rheumatology

Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3). (PubMed, Ann Rheum Dis) - P3 | "Otilimab demonstrated an acceptable safety profile but failed to achieve the primary end point of ACR20 and improve secondary end points versus placebo or demonstrate non-inferiority to sarilumab in this patient population."

Journal • P3 data • Fatigue • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology • CSF2

Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2). (PubMed, Ann Rheum Dis) - P3 | "Although otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib."

Journal • P3 data • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CSF2

contRAst X: Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P3 | N=2916 | Terminated | Sponsor: GlaxoSmithKline | Completed ➔ Terminated; Study is early terminated due to Limited efficacy demonstrated in the contRAst program does not support a suitable benefit/risk profile for otilimab as a potential treatment for RA. GSK has decided not to progress with regulatory submissions.

Trial termination • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Serum collagen biomarkers are related to fatal outcome in patients with severe COVID-19 in a Phase II clinical trial (ERS 2023) - P2 | " Serum was collected from patients enrolled in the Otilimab in Severe COVID-19 Related Disease (OSCAR) trial (NCT04376684)... Elevated serum levels of PRO-C3 at day 1 and increasing levels of PRO-C3 and PRO-C6 over time were related to mortality in patients with severe COVID-19. These markers may reflect a subgroup of patients who could benefit from anti-fibrotic treatment.; Cell and molecular biology; Respiratory intensive care; Physiology; Imaging; Pulmonary function testing"

Biomarker • Clinical • P2 data • Critical care • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

contRAst X: Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P3 | N=2916 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

contRAst 2: Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs) (clinicaltrials.gov) - P3 | N=1764 | Terminated | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Terminated; Only Asia cohort is early terminated.Limited efficacy demonstrated in the contRAst program does not support a suitable benefit/risk profile for otilimab as a potential treatment for RA. GSK has decided not to progress with regulatory submissions.

Combination therapy • Trial termination • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP • CSF2

A Study in Healthy Japanese Participants to Evaluate the Safety and Pharmacokinetics of Otilimab (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: GlaxoSmithKline | N=12 ➔ 0 | Trial completion date: Jun 2022 ➔ May 2023 | Initiation date: Mar 2022 ➔ Feb 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jun 2022 ➔ May 2023

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

contRAst X: Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P3 | N=2916 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

contRAst X: Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P3 | N=3000 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Apr 2024 ➔ Feb 2023 | Trial primary completion date: Apr 2024 ➔ Feb 2023

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

".@GSK licensed global rights to #otilimab in 2013, paying @MorphoSys €22.5 million up front. Another €423 million in payments were tied to milestones. Shares of $MOR dipped a bit on the $GSK news." (@frankvinluan)

GSK, MorphoSys’ Licensing Partner, Provides Update on ContRAst Phase III Program for Otilimab in Moderate to Severe Rheumatoid Arthritis (Morphosys Press Release) - P3 | N=550 | contRAst 3 (NCT04134728) | Sponsor: GlaxoSmithKline | "MorphoSys AG...announced today that its licensing partner, GSK plc...provided an update on the ContRAst phase III program for otilimab as a potential treatment of moderate to severe rheumatoid arthritis (RA)....Data from ContRAst-3, the third trial in the program, did not demonstrate statistical significance on the primary endpoint of ACR20 response versus placebo at week 12 in patients with inadequate response to biologic DMARDs and/or Janus Kinase inhibitors. According to GSK, assessment of efficacy and safety data from the ContRAst program is ongoing, however the limited efficacy demonstrated does not support a suitable benefit/risk profile for otilimab as a potential treatment to transform patient care for this difficult-to-treat population of RA patients. As a result, GSK has decided not to progress with regulatory submissions..."

Discontinued • P3 data • Immunology • Rheumatoid Arthritis

contRAst 2: Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs) (clinicaltrials.gov) - P3 | N=1764 | Active, not recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Sep 2022 ➔ Feb 2023

Combination therapy • Trial completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP • CSF2

contRAst 1: Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (clinicaltrials.gov) - P3 | N=1537 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP • CSF2

"As a result of GSK's PhII otilimab trial failing to meet its one of its three endpoints, the pharma is scrapping plans for regulatory submissions. https://t.co/w2WoNmr3GD" (@endpts)

A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR). (PubMed, Eur Respir J) - P2 | "There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile."

Journal • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CRP • CSF2

Otilimab: Acceptance of regulatory submissions in US/EU for rheumatoid arthritis (based on contRAst trial) in H2 2023 (GSK) - Q2 2022 Results

BLA • European regulatory • Immunology • Rheumatoid Arthritis

Otilimab: Regulatory submission for rheumatoid arthritis (based on contRAst trial) in 2023 (GSK) - Q1 2022 Results

Regulatory • Immunology • Rheumatoid Arthritis

A Study in Healthy Japanese Participants to Evaluate the Safety and Pharmacokinetics of Otilimab (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

contRAst 3: Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors (clinicaltrials.gov) - P3 | N=550 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP • CSF2

Detection and Modulation of Olfactory Sensing Receptors in Carnivorous Rainbow Trout (Oncorhynchus mykiss) Fed from First Feeding with Plant-Based Diet. (PubMed, Int J Mol Sci) - "Gene expression after feeding demonstrated the importance in olfactory sensing perception of some OLFC (olfcg6) and MOR (mor103, -107, -112, -113, -133) receptor family genes in RT...Results indicated an impact of a plant-based diet on the regulation of olfactory sensing pathways as well as influence on monoaminergic neurotransmission in brain areas related to olfactory-driven behaviors. The overall findings suggest that feeding behavior is mediated through olfactory sensing detection and olfactory-driven behavior pathways in RT."

Journal

Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P3; N=3000; Recruiting; Sponsor: GlaxoSmithKline; Trial completion date: Sep 2023 ➔ Apr 2024; Trial primary completion date: Sep 2023 ➔ Apr 2024

Clinical • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

GSK side-lines COVID drug otilimab to focus on Xevudy (pharmaphorum) - "GlaxoSmithKline said today it would halt further development of its antibody for severe COVID-19 pneumonia – otilimab – in order to focus its resources on Xevudy for mild-to-moderate disease...had been in clinical testing to see if it could treat severe pulmonary COVID-19 related disease in patients 70 years and older, and had shown signs of improving survival in a phase 2 trial reported earlier this year....GSK also revealed that Xevudy had generated £130 million (around $179 million) in sales in the first nine months of the year, with £114 million of that total coming in the third quarter...It already has binding agreements in place for the sale of more than 420,000 doses of Xevudy, with an additional 220,000 doses reserved through other agreements."

Discontinued • Sales • Infectious Disease • Novel Coronavirus Disease

contRAst 2: Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Drugs (DMARDs) (clinicaltrials.gov) - P3; N=1674; Active, not recruiting; Sponsor: GlaxoSmithKline; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP • CSF2