A Parallel-group Treatment, Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Umbrella Study to Evaluate the Efficacy and Safety of Frexalimab, SAR442970, and Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)

This is a parallel, Phase 2a, double-blind, 6-arm study for the treatment of primary focal segmental glomerulosclerosis (FSGS) or primary minimal change disease (MCD).
The purpose of this study is to measure the change in proteinuria and its impact on the rates of remission of nephrotic syndrome with frexalimab, SAR442970, or rilzabrutinib compared with placebo in participants with primary FSGS or primary MCD aged 16 to 75 years.
Study details for each participant include:
The study duration will be up to 76 weeks. The treatment duration will be 24 weeks. There will be up to 18 visits.

Start Date22 Aug 2024

Sponsor / Collaborator

Sanofi

JPRN-jRCT2071230056 / Not yet recruitingPhase 1IIT

A Phase 1, open-label, randomized, 2-arm, parallel design study to evaluate the pharmacokinetics, safety, and tolerability of single subcutaneous dose of SAR442970 in healthy adult Japanese participants

Start Date26 Sep 2023

Sponsor / Collaborator-

NCT05849922 / Active, not recruitingPhase 2

A Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study Assessing the Efficacy and Safety of an Anti-TNF-OX40L NANOBODY® Molecule, SAR442970, in Participants With Moderate to Severe Hidradenitis Suppurativa

This is a Phase 2 study in adult participants with moderate to severe hidradenitis suppurativa (HS). The purpose of the study is to evaluate the efficacy and safety of SAR442970 compared to placebo.

Start Date06 Jun 2023

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Brivekimig

100 Translational Medicine associated with Brivekimig

100 Patents (Medical) associated with Brivekimig

Literatures (Medical) associated with Brivekimig

15 Oct 2024·The Journal of clinical endocrinology and metabolism

Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis

Article

Author: Du, Xuan ; Shi, Bimin ; Zhu, Yan ; Lu, Wen ; Wang, Qin ; Fu, Nannan

Abstract:

Objective/Main Outcome:

To study the expression of OX40 on T follicular helper (Tfh) cells and the ligand OX40L on antigen-presenting cells (APCs) in peripheral blood of patients with type 1 diabetes mellitus (T1DM) and the role of OX40 signaling in promoting Tfh cells to assist B-cell differentiation.

Design:

Cross-sectional study.

Setting:

Endocrinology department of a university hospital.

Participants:

Twenty-five patients with T1DM and 35 with newly diagnosed type 2 diabetes mellitus (T2DM) from January 2021 to December 2021 (39 males, 21 females; mean age: 31.0 ± 4.5, range: 19-46 years).

Interventions:

None.

Methods:

The peripheral blood proportion of CD4+CD25−CD127+CXCR5+PD1+ Tfh cells in patients with T1DM or T2DM and the OX40L expression in CD14+ monocytes and CD19+ B cells were analyzed by flow cytometry. The OX40 signal effect on Tfh-cell function was analyzed by coincubating B cells with Tfh cells under different conditions. Flow cytometry detected the ratio of CD19−CD138+ plasmacytes.

Results:

The Tfh cells ratio and intracellular IL-21 expression in peripheral blood was significantly higher in patients with T1DM than with T2DM, and the OX40 expression in peripheral Tfh cells and OX40L expression in APC were significantly higher in T1DM. After adding OX40L protein, the CD19−CD138+-plasmacytes percentage was significantly increased and higher in T1DM. Blocking of anti-OX40L monoclonal antibodies significantly reduced the plasmacytes ratio.

Conclusion:

The peripheral Tfh cells proportion increased and the OX40 expression in peripheral Tfh cells was upregulated in patients with T1DM vs patients with T2DM. OX40/OX40L signaling enhanced the Tfh-cell function to assist B-cell differentiation, which may contribute to the pathogenesis of T1DM.

01 Jun 2024·Allergy

Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs

Review

Author: Müller, Svenja ; Bieber, Thomas ; Maintz, Laura

Abstract:

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti‐interleukin‐4 receptor (IL‐4R) α in 2017), tralokinumab (anti‐IL‐13 in 2021), lebrikizumab (anti‐IL‐13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long‐term safety, and efficacy. Upadacitinib and abrocitinib have the highest short‐term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long‐term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan‐JAKi), asivatrep (anti‐transient receptor potential vanilloid), and phosphodiesterase‐4‐inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord‐blood‐derived mesenchymal stem cells, CM310 (anti IL‐4Rα), nemolizumab (anti‐IL‐31RA), anti‐OX40/OX40L‐antibodies, neurokinin‐receptor‐1‐antagonists, and difelikefalin (κ‐opioid‐R) are reported.

25 Oct 2023·The British journal of dermatology

Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial

Article

Author: Brennan, Nuala ; Weidinger, Stephan ; Gilbert, Sally ; Reich, Adam ; Porter-Brown, Ben ; O’Malley, John T ; Quaratino, Sonia ; Cork, Michael J ; Wilson, Rosamund ; Stebegg, Marisa ; Bieber, Thomas

Abstract:

Background:

Atopic dermatitis (AD) is an inflammatory skin disease with significant unmet need. Blockade of the OX40–OX40 ligand (OX40L) costimulation pathway by targeting OX40L on antigen-presenting cells (APCs) with a fully human noncytotoxic, nondepleting anti-OX40L monoclonal antibody (amlitelimab; SAR445229; KY1005) is a novel way to modulate persistent inflammation.

Objectives:

To assess the safety and efficacy of amlitelimab over 16 weeks in adults with AD in a phase IIa double-blind placebo-controlled study.

Methods:

The study was conducted at 19 hospitals in Germany, Poland, Spain and the UK. Eligible patients with moderate-to-severe AD were randomized (1 : 1 : 1) to low-dose intravenous (IV) amlitelimab (200 mg), high-dose IV amlitelimab (500 mg) or placebo, followed by three maintenance doses (50% of loading dose) at 4, 8 and 12 weeks, with safety follow-up to week 36. The co-primary endpoints were the incidence of treatment-emergent adverse events (all patients who received ≥ 1 dose of the study drug) and mean percentage change in Eczema Area and Severity Index (EASI) to week 16 (full analysis set).

Results:

Between 13 December 2018 and 12 May 2020, 89 patients were randomly assigned to low- (n = 29) or high-dose amlitelimab (n = 30) or placebo (n = 29), of whom 88 proceeded to treatment [37 women (42%), 51 (58%) men; mean (SD) age 33.6 (11.9) years]. Amlitelimab was generally well tolerated with an unremarkable safety profile; no hypersensitivity events were reported. For the primary endpoint, the least square mean percentage change in EASI from baseline to week 16 was –80.12% [95% confidence interval (CI) –95.55 to –64.68; P = 0.009 vs. placebo] and –69.97% (95% CI –85.04 to –54.60; P = 0.07 vs. placebo) for the low- (n = 27) and high-dose (n = 27) amlitelimab groups, respectively, vs. –49.37% (95% CI –66.02 to –32.72) for placebo (n = 24). Numerically greater reductions in EASI were observed for amlitelimab vs. placebo from weeks 2 to 16.

Conclusions:

Novel targeting of OX40L-expressing APCs with amlitelimab was well tolerated and resulted in clinically meaningful improvements in AD.

News (Medical) associated with Brivekimig

09 Oct 2024

·www.globenewswire.com

Inmagene to Host Virtual KOL Event on the Inhibition of the OX40/OX40L Signaling in the Treatment of Atopic Dermatitis and Alopecia Areata

SAN DIEGO, Oct. 09, 2024 (GLOBE NEWSWIRE) -- Inmagene Biopharmaceuticals (Inmagene), a clinical-stage biotechnology company developing innovative and differentiated therapies for immunological and inflammatory (I&I) diseases, today announced it will host a virtual key opinion leader (KOL) event at 10:00 AM ET on Thursday, October 31, 2024. To register, click here. The event will feature Jonathan Silverberg, MD, PhD, MPH (The George Washington University School of Medicine and Health Sciences), Maryanne Senna, MD (Beth Israel Lahey Health, Harvard Medical School), and Yufang Lu, MD, PhD (Inmagene) who will discuss the potential role of anti-OX40/OX40L monoclonal antibodies (mAbs) in the treatment of atopic dermatitis (AD) and alopecia areata (AA). The event will discuss data from emerging OX40/OX40L inhibitors, including Inmagene’s IMG-007 - the only clinical-stage non-depleting anti-OX40 mAb. A live question and answer session will follow the formal presentations. About Jonathan Silverberg, MD, PhD, MPHJonathan Silverberg, MD, PhD, MPH is an Associate Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC. He is the Director of Clinical Research and Contact Dermatitis. Dr. Silverberg completed his undergraduate and medical school training as a part of the highly selective dual B.A./M.D. program at State University of New York Downstate Medical Center, in Brooklyn. Dr. Silverberg also received his doctorate in neuroimmunology and Master of Public Health degree in biostatistics and epidemiology from the State University of New York Downstate Medical Center where he also completed his internship in internal medicine. He completed his residency training in dermatology at St. Luke's-Roosevelt Hospital Center and Beth Israel Medical Centers in New York, NY and served as Chief Resident during his final year. Dr. Silverberg's area of clinical subspecialty is inflammatory skin disease, particularly atopic and contact dermatitis. He has extensive experience in the advanced management of atopic dermatitis, hand eczema, chronic itch, psoriasis, hidradenitis and many other chronic inflammatory skin disorders. He is also a national expert in allergy patch testing, phototesting and photopatch testing. Dr. Silverberg's research interests include drug development, clinical trial design, biomarkers, dermato-epidemiology, health services research, patient-reported outcomes, comorbidities and burden of itch and inflammatory skin disease and evidence-based dermatology. His publications include more than 600 peer-reviewed articles, abstracts and book chapters. He is also the author of the Clinical Management of Atopic Dermatitis handbook (2018). Dr. Silverberg has also been a local, national and/or international principal investigator for numerous clinical trials for novel treatments in atopic dermatitis and other inflammatory disorders. He has been recognized with several honors, including the Young Leadership Award from the American Dermatological Association in 2017, Teacher of the Year Award in the department of dermatology in 2015, Outstanding Teacher's Award from the Feinberg School of Medicine in 2016, 2017 and 2018, and the inaugural Rajka Award from the International Society for Atopic Dermatitis in 2014. He is an associate editor for the Journal of the American Academy of Dermatology, British Journal of Dermatology and Current Dermatology Reports. Dr. Silverberg is a member of the International Eczema Council, North American Contact Dermatitis Group the American Society of Contact Dermatitis. Dr. Silverberg is also the chair of the annual Revolutionizing Atopic Dermatitis global multidisciplinary conference. About Maryanne Senna, MDMaryanne Senna, MD is a board-certified dermatologist at Beth Israel Lahey Health, and assistant professor of dermatology at Harvard Medical School. Dr. Senna founded and directs the Lahey Hair Loss Center of Excellence and serves as principal of the research unit. Prior to this role, she founded the MGH Hair Loss Clinic and clinical trials unit, which she ran for nearly 10 years. She has held a number of pharmaceutical, device, and foundation appointments. Widely published and recognized for her clinical expertise, teaching, and research, Dr. Senna is frequently invited to speak and give lectures nationally and abroad, and has been quoted in top-tier media publications such as The New York Times and The Atlantic. She has also been featured on multiple news outlets including Good Morning America, and in the HBO Max documentary series Not So Pretty. Dr. Senna is an esteemed member of several professional societies and committees, and is on the board of directors of the Scarring Alopecia Foundation, the American Hair Research Society, and on the medical advisory task force for the National Alopecia Areata Foundation. About Yufang Lu, MD, PhDYufang Lu is the Chief Medical Officer of Inmagene. Dr. Lu is an accomplished physician scientist with more than 20 years of experience in clinical development and medical affairs. She has successfully led clinical development for both small molecules and biologics across diverse therapeutic areas, including dermatology, allergy, gastroenterology, and rheumatology. Prior to Inmagene, Dr. Lu was Vice President of Clinical Development at Celldex, where she drove the advancement of innovative immunology assets, including barzovolimab. During her tenure at Regeneron, she led cross-functional medical teams in the global launches of Dupixent® in atopic dermatitis and asthma. Earlier in her career, she held roles in clinical development and medical affairs at Celgene, Eisai, and GSK. Dr. Lu received her medical degree from Nanjing Medical University with residency training in dermatology and a PhD in toxicology from Texas A&M University. About InmageneInmagene is a global clinical-stage biotechnology company developing novel therapeutics for I&I diseases. The company’s highly differentiated clinical-stage pipeline has multiple candidates with best-in-class potential. The lead asset IMG-007, a non-depleting anti-OX40 mAb, is in two global Phase 2a clinical trials in atopic dermatitis and alopecia areata. IMG-004, a non-covalent reversible BTK inhibitor with an extended half-life and pharmacodynamic effect, enabling its potential for once-daily dosing, recently completed the Phase 1 multiple ascending dose (MAD) study and is ready for Phase 2 development. For more information, please visit www.inmagenebio.com. About IMG-007IMG-007 is a humanized anti-OX40 IgG1 mAb, with an extended half-life and silenced antibody-dependent cellular cytotoxicity (ADCC) function. In nonclinical studies, IMG-007 potently blocked the signalling between OX40 and OX40L. IMG-007 is being evaluated for the treatment of moderate-to-severe atopic dermatitis (AD) and severe alopecia areata (AA). In a Phase 2a study in AD patients, a short 4-week treatment with IMG-007 resulted in a rapid and marked improvement in the extent and severity of skin lesions in AD patients. Interim data from a pharmacokinetic study showed that subcutaneous IMG-007 demonstrated an exceptionally long half-life, which would enable its potential for every six months (Q6M) dosing for AD maintenance therapy. Separately, its silenced ADCC function has led to a favorable safety profile, without any reports of pyrexia and chills, differentiating it from a competing ADCC-enhanced anti-OX40 mAb. Inmagene has in-licensed IMG-007’s exclusive global rights from HUTCHMED. Forward-Looking StatementsThis press release contains forward-looking statements. While Inmagene believes the projections to be based on reasonable assumptions, these forward-looking statements may be called into question by a number of hazards and uncertainties, so that actual results may differ materially from those anticipated in such forward-looking statements. For further information, please contact:Inmagene:Anna Vardanyan, MD, PhDSVP of Corporate and Business Developmentvardanyana@inmagenebio.com Investor Relations:Bruce MackleLifeSci Advisors, LLCbmackle@lifesciadvisors.com

Phase 2Phase 1Clinical Result

25 Apr 2024

·firstwordpharma.com

AbbVie's Rinvoq again tops Dupixent in head-to-head atopic dermatitis trial

Sanofi and Regeneron Pharmaceuticals' dual IL-3 and IL-14 blocker Dupixent (dupilumab) is firmly entrenched as an initial-line treatment option for moderate-to-severe atopic dermatitis, but for the second time, AbbVie's JAK inhibitor Rinvoq (upadacitinib) has outperformed its rival in a head-to-head match-up.On Thursday, AbbVie toplined results from the Phase IIIb/IV LEVEL UP trial showing that its drug outperformed Dupixent in adult and adolescent patients who had inadequate response or were considered unsuitable for systemic therapies.Both drugs are already approved for atopic dermatitis; Dupixent got a head start with a US green light back in 2017. The drug's sales reached €2.8 billion in the first three months of this year, according to financial results reported by Sanofi on Thursday.Meanwhile, Rinvoq finally scored an approval for the indication in 2022 after safety concerns with JAKs as a class held back its application at the FDA.Better skin clearance, itch reliefThe 16-week LEVEL UP study is designed to randomise up to 880 patients to receive either once-daily oral Rinvoq or Dupixent injections given every other week following an initial dose.For the study's primary endpoint, 19.9% of patients on Rinvoq simultaneously achieved ≥90% reduction on the Eczema Area and Severity Index (EASI 90) along with no or minimal itch based on the Worst Pruritus Numerical Rating Scale 0/1 at week 16. That compares with just 8.9% for the Dupixent arm.Rinvoq also demonstrated superiority across all ranked secondary endpoints, including 40.8% of patients achieving EASI 90 at week 16 versus 22.5% of those on Dupixent. For itch resolution over the same period, the rates were 30.2% and 15.5% for the two drugs, respectively.Safety-wise, AbbVie said Rinvoq's profile in LEVEL UP was consistent with prior atopic dermatitis studies, with rates of serious adverse events at less than 1% for both groups. In a recent interview with FirstWord, key opinion leader Gilberto Alvarez del Manzano indicated that he was "not too concerned about safety with JAK inhibitors in the right population."Rinvoq prevails againThe LEVEL UP data adds to previous head-to-head results from the Phase IIIb HEADS UP study, unveiled in late 2020, where Rinvoq also showed superiority over Dupixent across the primary and secondary endpoints in atopic dermatitis.While Dupixent maintains its stronghold, the landscape is shifting as new oral and injectable competitors with more convenient dosing regimens angle for a share of the dermatitis pie.At the recent American Academy of Dermatology (AAD) meeting, less-frequent dosing emerged as a major theme. Sanofi reported data supporting potential every-12-week dosing for its anti-OX40L antibody amlitelimab, while Galderma is considering every-eight-week dosing for its anti-IL-31 nemolizumab.Alvarez del Manzano noted that reducing injection frequency from every-other-week "would matter a lot" in driving uptake, adding that "many patients would rather inject than take a pill every day."

Clinical ResultDrug ApprovalPhase 3

13 Mar 2024

·www.fiercebiotech.com

Sanofi shutting down R&D site at UK biotech hub, displacing 90 workers

A Sanofi spokesperson said the pharma will try to find spots within the company for as many of the displaced staffers as possible. Sanofi will be closing the doors to a research facility in the biotech hub of Cambridge, U.K., a move that will impact around 90 people, a spokesperson for the French Pharma told Fierce Biotech. “Upon careful review of our R&D global footprint, we are proposing to end research operations in Cambridge, U.K., a site which joined our company through acquisition in 2021,” the Sanofi spokesperson told Fierce in an emailed statement March 13. The site previously belonged to antibody developer Kymab, a biotech that Sanofi acquired in 2021 for $1.1 billion upfront. The deal centered around an anti-OX40L monoclonal antibody designed to improve outcomes in patients with atopic dermatitis. That drug hit the main goals of a phase 2b trial last June, spurring talks of a phase 3 launch. Despite that clinical success, it hasn't convinced Sanofi to maintain a footprint in Cambridge, a hub of biotech activity in the U.K. that is also the location of AstraZeneca's headquarters. Around 90 people are employed at the Sanofi R&D site, all of whom have been informed of the closure, the spokesperson said. The Paris-based pharma will try to find a place within Sanofi for as many of the staffers as possible, the spokesperson added. The shuttering follows a strategy shift for Sanofi. The Big Pharma has decided to funnel cash into key programs rather than increase its operating profit margin, CEO Paul Hudson announced in October. In December, the company tipped three "pipeline-in-a-product” assets to generate 5 billion euros ($5.4 billion) in a year or more, one of several predictions intended to justify the decision to ditch its margin target. In better news for Cambridge's pharma credentials, AstraZeneca revealed last week that it will invest 200 million pounds sterling ($256 million) to expand the company's presence near its global headquarters. The plan includes a facility that will house around 1,000 employees, the drugmaker said.

AcquisitionPhase 2

100 Deals associated with Brivekimig

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulosclerosis (disorder)	Phase 2	US	Sanofi	22 Aug 2024
Glomerulosclerosis, Focal Segmental	Phase 2	US	Sanofi	22 Aug 2024
Nephrosis, Lipoid	Phase 2	US	Sanofi	22 Aug 2024
Hidradenitis Suppurativa	Phase 2	US	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	AU	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	BE	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	CA	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	CL	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	CZ	Sanofi	06 Jun 2023
Hidradenitis Suppurativa	Phase 2	DK	Sanofi	06 Jun 2023

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