rontalizumab (RG7415) / Roche - LARVOL DELTA

Targeting Type I IFN in SLE and lupus nephritis (LUPUS 2024) - "Although rontalizumab and sifalimumab, the first two monoclonal antibodies directed against interferon alpha to be evaluated in clinical trials, yielded negative and modest clinical trial results, respectively, other pursuits were undertaken that proved more fruitful. The anifrolumab program reaffirmed the clinical significance of type I IFN in SLE and boosted confidence that other approaches to inhibit type I IFN would prove efficacious. This presentation will review various strategies being pursued in order to block the interferon pathway in SLE and lupus nephritis."

Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • IFNA1 • IFNAR2

S95021, a novel selective and pan-neutralizing anti interferon alpha (IFN-α) monoclonal antibody as a candidate treatment for selected autoimmune rheumatic diseases. (PubMed, J Transl Autoimmun) - "S95021 was IFN-α-selective and exhibited superior potency and broader neutralization profile when compared with the benchmark anti-IFN-α mAbs rontalizumab and sifalimumab. Together, our results show that S95021 is a new potent, selective and pan IFN-α-neutralizing mAb. It is currently further evaluated as a valid therapeutic candidate in selected autoimmune diseases in which the IFN-α pro-inflammatory pathway is dysregulated."

Journal • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • STAT1

[VIRTUAL] Efficacy of Biological Agents for the Management of Systemic Lupus Erythematosus: A Systematic Review and Network Meta-Analysis (CRA-AHPA 2021) - "These 20 RCTs investigated the following biologics: belimumab, anifrolumab, ustekinumab, atacicept, baricitinib, blisibimod, epratuzumab, IL-2, lupuzor, PF-04236921, rontalizumab, sifalimumab, and tabalumab... The NMA identified that belimumab, anifrolumab and ustekinumab demonstrated greater response in comparison to placebo, when measured using SRI. This systematic review identified that there was heterogeneity in the outcome measures and endpoints used. In the future, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be applied to rate the quality of the evidence, and to gain insight into methodological pitfalls that could have negatively altered the results of RCTs."

Retrospective data • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • IL2

Reasons to be cheerful: One, two, three? (BSR 2017) - "Three different monoclonal antibodies (Rontalizumab, Silfalimumab and Anifrolumab) have been used in major clinical trials in SLE. For example, the importance of an increased interferon-alpha signature in the development of SLE is widely recognised. However other ongoing phase II trials utilising a novel recombinant FcɣIIB receptor [SM101] and RNP peptide (Lupuzor previously known as PI140) are now underway after encouraging animal-model and/or phase I studies. Benlysta which blocks the B-cell activating factor BAFF remains the only biologic to be formally approved in the UK and the USA for the treatment of lupus albeit under significant restrictions. Frustratingly, other approaches, for example, the use of Abatacept which blocks the antigen-presenting cell-T-cell interaction have not met their endpoints in clinical trials. In retrospect the significantly heterogeneous nature of lupus was always likely to make it more challenging to respond to individual biologic approaches. ...

Biosimilar • Immunology • Lupus • Psoriasis • Rheumatoid Arthritis

Structural Basis of the Broadly Neutralizing anti-Interferon-α Antibody Rontalizumab. (PubMed) - "Anti-IFN-α antibodies including rontalizumab have been under clinical study for the treatment of lupus. To better understand the rontalizumab mechanism of action and specificity, we determined the X-ray crystal structure of the Fab fragment of rontalizumab bound to human IFN-α2 at 3Å resolution and find substantial overlap of the antibody and IFNA2 epitopes on IFN-α2."

Journal • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

FY 2010 results (Roche) - rontalizumab (RG 7415) / Roche; Anticipated NME submission for SLE in post 2013

Anticipated NME submission • Immunology

Half year results, 2010 (Roche) - Rontalizumab / Roche; Expected to complete enrolment in H2’ 10 for P2 ROSE for SLE, NME submission expected in US & EU for SLE post ‘13

Regulatory update

Safety and pharmacodynamic results of rontalizumab in a phase I, placebo controlled, double blind, dose escalation study in systemic lupus erythematosus (Arthritis Rheum) - P1, N=60; NCT00541749; Rontalizumab demonstrated an acceptable safety profile in SLE pts; Pre-specified criteria for dose limiting toxicity were not met; Incidence of serious adverse events was comparable across cohorts; PK properties were as expected for an IgG1 & dose proportional; Preliminary safety, PK profile & observed PD effects of rontalizumab support further evaluation of its safety & efficacy in SLE

P1 data • PK/PD data • Immunology • Lupus

Efficacy and safety of rontalizumab (anti-interferon alpha) in SLE subjects with restricted immunosuppressant use: Results of a randomized, double-blind, placebo-controlled phase 2 study (ACR/ARHP 2012) - P2, N=238; ROSE; Rontalizumab vs. PBO SLE Response index (SRI) response rates were 75% vs. 18% & 75% vs. 62% in the IV & SC groups, respectively; The estimated treatment difference of SRI response in rontalizumab & PBO ISM-Low arms was 31% (p=0.0285); A reduction in SS flare rates occurred in rontalizumab subjects vs. PBO (p=0.0040) driven by ISM-Low subjects; Rontalizumab treatment in absence of immunosuppressants was associated with improvement in signs & symptoms of SLE, flare rates & steroid burden at week 24

P2 data • Immunology • Lupus

Oppenheimer Healthcare Conference (Roche) - Anticipated filing for lupus in 2017 or later

Anticipated regulatory • Immunology • Lupus

Roche pipeline updated (Roche Press Release) - Removed from pipeline for development in SLE on July 24, 2014.

Discontinued • Immunology • Lupus

Efficacy and safety of rontalizumab (anti-interferon-alpha) in SLE patients with restricted immunosuppressant use: Results of a randomized, doubleblind, placebo-controlled phase 2 study (Lupus 2013) - Abstract# O22; Presentation Time: 20/04/13; 10:40 - 11:40; P2, N=238; ROSE (NCT00962832); "The estimated treatment difference of SRI response in rontalizumab and placebo ISMLo arms was 31% (...p=0.0285). Exploratory results with the more stringent SRI6 response were 41% vs. 9%, and 69% vs. 31% in the IV and SC groups, respectively. A reduction in SS flare rates occurred in rontalizumab patients vs. placebo: hazard ratio 0.61 (...p=0.0040), driven by ISMLo patients."

P2 data • Immunology • Lupus

Rontalizumab therapy found to offer a clinical benefit to particular group of lupus patients (Lupus News Today) - P2, N=238; ROSE (NCT00962832); Sponsor: Genentech; "The clinical efficacy endpoints were the decrease in disease activity assessed by the British Isles Lupus Disease Activity Group (BILAG)-2004 (primary) and SLE response index (SRI, secondary) at 24 weeks after treatment."

P2 data • Immunology • Lupus

Validation of the revised selena flare index in systemic lupus erythematosus (ACR-ARHP 2013) - Presentation time: Tuesday, October 29, 2013; 8:30 am - 4:00 pm; Abstract #2542; P2, N=235; ROSE (NCT00962832); Sponsor: Genentech; "The agreement between rSFI and SFI was better for the clinical part of the rSFI (kappa 0.69) than the treatment part of rSFI (kappa 0.35). The SFI showed fair agreement (kappa 0.30; weighted 0.39) and the rSFI showed moderate agreement (kappa 0.31; weighted 0.51) with the BILAG flare index."

P2 data • Immunology • Lupus

Investor Day (Roche) - Anticipated P2 data readout at ACR for lupus in November 2012

Anticipated P2 data • Immunology • Lupus

Validation of the revised SELENA flare index in systemic lupus erythematosus (EULAR 2013) - Presentation time: 14.06.2013, 11:45; Abstract #FRI0293; P2, N=237; Sponsor: Genentech; ROSE (NCT00962832); "The SFI showed fair agreement (kappa 0.30; weighted 0.39) and the rSFI showed moderate agreement (kappa 0.31; weighted 0.51) with the BILAG flare index. Many of the significant discrepancies between instruments (e.g., mild flare by rSFI, but severe by the BILAG flare index) were determined, after further review, to be correctable data reporting errors."

P2 data • Immunology • Lupus

Anifrolumab in systemic lupus erythematosus: current knowledge and future considerations. (PubMed, Immunotherapy) - "Anifrolumab, a human monoclonal antibody against the type I IFN receptor, has recently been evaluated in two Phase III clinical trials for the treatment of moderate-to-severe SLE. Here, we review the clinical efficacy and safety of anifrolumab and discuss the potential challenges in determining the optimal SLE patient subgroup for treatment."

Journal

Recognition and management of systemic lupus erythematosus - "Hydroxychloroquine is typically well tolerated at the rec-ommended dose of lessthan 5mg per kg real body weightto minimise toxicity....Although not licensed for SLE treatment, methotrexate 7.5-15mg per week can be used in order to control inflammatory arthritis and lupus skin rashes....There is also increasing interest in the notion that rituximab followed by mycophenolate or azathioprine could be used at the time of lupus diagnosis, replacing oral steroids (which cause many side-effects) altogether."

Online posting