Kevzara (sarilumab) / Asahi Kasei, Regeneron, Sanofi - LARVOL DELTA

A phase II study of the interleukin-6 (IL-6) receptor blocking antibody sarilumab (Sari) in combination with ipilimumab (Ipi), nivolumab (Nivo) and relatlimab (Rela) in patients with unresectable stage III or stage IV melanoma. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05428007 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • IL6

A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER) (clinicaltrials.gov) - P1/2 | N=65 | Recruiting | Sponsor: University of Southern California | Trial completion date: Nov 2026 ➔ Sep 2027 | Trial primary completion date: Nov 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

Abatacept, Golimumab, and Sarilumab as Selected Bio-Originator Disease-Modifying Antirheumatic Drugs with Diverse Mechanisms of Action in Their Current Use in Treatment. (PubMed, J Clin Med) - " Treating arthritis continues to be challenging due to its numerous underlying causes and the varied ways in which patients respond to treatment. Although biologics and targeted therapies have brought progress, additional research is needed to identify new treatment targets and enhance patient results."

Journal • Review • Gout • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Anti-Rheumatic potential of biological DMARDS and protagonistic role of bio-markers in early detection and management of rheumatoid arthritis. (PubMed, Innate Immun) - "Non-tumor necrosis factor inhibitors (Non-TNFi) such as abatacept, rituximab, tocilizumab, and sarilumab are examples, as are anti-tumor necrosis factor (TNF) medications such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. The assessment of RA treatment response typically combines patient-reported outcomes, physical evaluations, and laboratory findings, as there isn't a single biomarker that has proven sufficient for measuring disease activity. This review explores the usage of biologic DMARDs as a therapeutic approach for RA, as well as the biomarkers typically used for RA early diagnosis, prognosis prediction, and disease activity evaluation."

Biomarker • Journal • Review • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Advances in the treatment of polymyalgia rheumatica. (PubMed, Rheumatology (Oxford)) - "Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate, offer limited benefits, while recent evidence supports the use of biologics, such as tocilizumab and sarilumab, in reducing GC dependency and achieving remission. Emerging treatments, including JAK inhibitors (tofacitinib) and B-cell depletion (rituximab), show promise but require further validation. The treat-to-target (T2T) strategy is advocated for achieving sustained remission and minimizing adverse effects. New treatment options requiring rheumatological expertise are emerging, highlighting the need for specialized management, early referral, improved imaging use, and standardized definitions of remission and relapse to enhance patient care and outcomes."

Journal • Review • Giant Cell Arteritis • Immunology • Inflammation • Musculoskeletal Pain • Pain • Rheumatology

BIO3: Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients with Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide (clinicaltrials.gov) - P4 | N=286 | Recruiting | Sponsor: University Hospital, Strasbourg, France | Trial completion date: Mar 2025 ➔ Mar 2029 | Trial primary completion date: Mar 2025 ➔ Mar 2029

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

Cost-effectiveness analysis of subcutaneous biosimilar tocilizumab in patients with rheumatoid arthritis in Spain. (PubMed, Farm Hosp) - "bsTCZ demonstrated to be a cost-effective and cost-saving alternative for the treatment of patients with RA in Spain when compared to all the available therapeutic alternatives."

HEOR • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Population Pharmacokinetics and Exposure-Response Analyses of Sarilumab in Patients with Polymyalgia Rheumatica. (PubMed, J Clin Pharmacol) - P3 | "There was a slight increase in patients achieving sustained remission at Week 52 and a decrease in absolute neutrophil count with increasing sarilumab Ctrough plateauing at 20-25 mg/L. The PD effect of sarilumab plateaued at Ctrough of 20-25 mg/L for target saturation, efficacy, and safety endpoints, supporting a dosage of 200 mg every 2 weeks for PMR."

Journal • PK/PD data • Giant Cell Arteritis • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Pain • Rheumatoid Arthritis • Rheumatology • CRP

Successful Salvage Therapy of Late-onset Arterial Disorders due to Recurrent Vasospasms Following Free Flap Transfer under the IL-6 and TNF-α Signaling-downregulated Environment: A Case Report. (PubMed, J Plast Reconstr Surg) - "A 77-year-old woman who had been taking iguratimod and sarilumab for rheumatoid arthritis for 3 months had gas gangrene...Recent developments in antirheumatic drug therapy have increased the chances of performing microvascular surgeries on patients with inhibited immune systems, and this trend will continue or will be reinforced in the future. Close monitoring of the biochemical and clinical status of the microvascular environment is necessary."

Journal • Cardiovascular • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • IL6 • TNFA

Kevzara: “Extension application to add a new strength of 175 mg/ml solution for injection in vial, grouped with an extension of indication to include treatment of active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older for KEVZARA, based on DRI13925…as a consequence, sections 1, 2, 3, 4.1, 4.2, 4.4, 4.8, 5.1, 5.2, 6.3, 6.5 and 6.6 of the SmPC are updated.” (European Medicines Agency) - CHMP Final Minutes of the meeting on 11- 14 Nov 2024: “The committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable”

CHMP • Idiopathic Arthritis • Immunology

Kevzara: “Extension of indication to include treatment of Polymyalgia Rheumatica in adult patients who have had an inadequate response to corticosteroids or who experience a relapse during corticosteroid taper, based on results from study EFC15160…as a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 6.1 of the SmPC are updated” (European Medicines Agency) - CHMP Final Minutes of the meeting on 14- 17 Oct 2024: “The committee adopted a positive opinion by consensus together with the CHMP assessment report and translation timetable”

CHMP • Immunology

Comparative effectiveness of subcutaneous sarilumab 200 mg biweekly, subcutaneous Tocilizumab 162 mg biweekly, and intravenous Tocilizumab 8 mg/kg every 4 weeks in patients with rheumatoid arthritis: a prospective cohort study. (PubMed, Arthritis Res Ther) - "SAR-SC 200 mg biweekly initiation was associated with a statistically significantly greater decrease in disease activity than TCZ-SC 162 mg biweekly in IL-6Ri-naïve patients with RA. In contrast, no statistically significant differences were identified between TCZ-IV 8 mg/kg every 4 week and TCZ-SC 162 mg biweekly. However, the effect size of our findings should necessitate careful consideration of the cost difference between TCZ-SC 162 mg biweekly including its biosimilars and SAR-SC 200 mg biweekly."

Clinical • HEOR • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Interleukin 6 inhibition in refractory antisynthetase syndrome: case-based literature review. (PubMed, Acta Clin Belg) - "In this manuscript we present two patients with insufficient response to conventional treatment who received tocilizumab and sarilumab, two bDMARDs targeting IL-6. The treatment was well tolerated. Future randomised clinical trials in a selected ASyS patient population could elucidate the efficacy of IL-6 inhibition in this specific IIM subgroup."

Journal • Review • Myositis • Rare Diseases • IL6

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

Nontraumatic terminal ileal perforation in a patient with resistant palindromic rheumatism treated with sarilumab: A case report. (PubMed, Reumatol Clin (Engl Ed)) - "Patients may present with acute abdominal pain and suspicion for this complication should remain high even in the absence of elevated C-reactive protein. We describe a 69-year-old female patient with a history of resistant seropositive palindromic rheumatism treated with sarilumab who developed a nontraumatic terminal ileal perforation."

Journal • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology • CRP • IL6

Phase 1/2 study of REGN4336 alone or in combination with cemiplimab or nezastomig in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2025) - P1/2 | "Module 1 began with REGN4336 administered SC; in addition, Modules 1–3 may evaluate REGN4336 administered IV (+ sarilumab [anti–IL-6] for CRS prophylaxis) to compare tolerability, PK, and immunogenicity across routes. This is the first study to evaluate combined ×CD3 + ×CD28 bsAb in mCRPC. As of Sept 12, 2024, 35 pts have been enrolled, including 4 in Module 3."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Effectiveness of baricitinib versus sarilumab on disease activity in patients with RA: a propensity score matching study. (PubMed, Rheumatol Adv Pract) - "At the component level, baricitinib significantly improved the number of swollen joints at 24 weeks, improving the Clinical Disease Activity Index; however, after 52 weeks, the difference between the two groups was no longer statistically significant. Compared with sarilumab, baricitinib improved swollen joints and the Clinical Disease Activity Index at 24 weeks; however, by 52 weeks, no significant difference was observed between the two groups, indicating that both treatments are important for long-term use."

Journal • Rheumatoid Arthritis • IL6

A Phase 2 Randomized Double-Blinded Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in Participants with Indolent Systemic Mastocytosis (AAAAI-WAO 2025) - "Other quality of life indices yielded similar results. Conclusions Results in this small trial did not support the use of sarilumab in this population and highlights the importance of double-blind randomized studies to investigate drug effects."

Clinical • HEOR • P2 data

Rheumatology: what's new in 2024 (PubMed, Rev Med Suisse) - "However, the necessary perspective is still lacking for a therapy that remains out of reach because of its price. On the other hand, the availability of targeted treatments offering real corticosteroid sparing benefits seems imminent for gigantocellular arteritis and polymyalgia rheumatica, with very promising results and treatments already used on a daily basis, notably JAK inhibitors, anti-IL17 and sarilumab."

Journal • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • IL17A

Terminal complement complex deposition on chondrocytes promotes premature senescence in age- and trauma-related osteoarthritis. (PubMed, Front Immunol) - "Explants were additionally treated with clusterin (CLU, TCC inhibitor), N-acetylcysteine (NAC, antioxidant), Sarilumab (IL-6 receptor inhibitor), STAT3-IN-1 (STAT3 inhibitor), or IL-1 receptor antagonist (IL-1RA) in order to investigate the consequences of TCC deposition. We provided evidence that the SIPS-like phenotype is more likely induced by TCC-mediated cytokine release rather than oxidative stress. Overall, targeting TCC formation could be a future approach to attenuate OA progression."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • CD59 • CDKN1A • CDKN2A • CLU • IL1B • IL6 • TP53

Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=220 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Oncology • Ovarian Cancer • Solid Tumor

Safety and Efficacy of Baricitinib, Upadacitinib, and Sarilumab Implementation in Moderately-to-Severely Active Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Current Evidence. (PubMed, Cureus) - "The newly approved JAK and IL-6 inhibitors, namely, baricitinib, upadacitinib, and sarilumab, seem to be effective in alleviating RA-induced clinical implications and thus improving quality of life. Nonetheless, safety issues could be a matter of concern in baricitinib use, while upadacitinib and sarilumab present an acceptable safety profile."

Journal • Retrospective data • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Understand How Effective is Tofacitinib When Compared to Other Advanced Treatments in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P=N/A | N=21340 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jul 2024 | Trial primary completion date: Dec 2024 ➔ Jul 2024

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

An Observational Study on Sarilumab-exposed Pregnancies (clinicaltrials.gov) - P=N/A | N=113 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

Kevzara: “Extension application to add a new strength of 175 mg/ml solution for injection in vial, grouped with an extension of indication to include treatment of active polyarticularcourse juvenile idiopathic arthritis in patients 2 years of age and older for KEVZARA, based on results from study DRI13925…as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated.” (European Medicines Agency) - CHMP Final Minutes of the meeting on 16- 19 Sep 2024: “The committee adopted the CHMP recommendation and scientific discussion together with the list of outstanding issues and a specific timetable”

CHMP • Idiopathic Arthritis • Immunology