A Phase 3, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group 48-week Extension Study to Evaluate the Treatment Response and Safety of Two Amlitelimab Dose Regimens Administered as Monotherapy by Subcutaneous Injection in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis

This is a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel, Phase 3 study for treatment of participants aged 12 years and older diagnosed with moderate-to-severe atopic dermatitis (AD).
The main objective of this study is to evaluate if those participants who received amlitelimab dose 1 in the parent studies (EFC17559 [COAST-1], EFC17560 [COAST 2], EFC17561 [SHORE]) and were responders can maintain their response either remaining at dose 1 or switching to dose 2 of amlitelimab compared to treatment withdrawal.
Study details include:
The study duration will be up to 64 weeks (for participants not entering the LTS17367 [RIVER-AD] study) including a 48-week randomized double-blind period, and a 16-week safety follow-up.
The study duration will be up to 48 weeks for participants entering the LTS17367 [RIVER-AD] study at the Week 48 visit of EFC17600 (ESTUARY).
The total treatment duration will be up to 48 weeks. The total number of visits will be up to 14 visits (or 13 visits for those entering LTS17367 [RIVER-AD] study).

Start Date08 May 2024

Sponsor / Collaborator

Sanofi

CTR20241420 / RecruitingPhase 3

一项 III 期、随机、双盲、安慰剂对照、平行组、3 组、多国家、多中心研究，旨在评价 18 岁及以上中重度特应性皮炎受试者皮下接受 amlitelimab 单药治疗的疗效和安全性。

[Translation] A phase III, randomized, double-blind, placebo-controlled, parallel-group, 3-arm, multinational, multicenter study was designed to evaluate the efficacy and safety of subcutaneous amlitelimab monotherapy in subjects 18 years and older with moderate to severe atopic dermatitis.

证明与安慰剂相比，18 岁及以上中重度特应性皮炎（AD）受试者接受 amlitelimab 单药皮下（SC）注射给药的疗效；评估与安慰剂相比，18 岁及以上中重度 AD 受试者接受 amlitelimab 单药皮下注射给药的疗效；评估 18 岁及以上中重度 AD 受试者接受 amlitelimab 单药皮下注射给药的安全性特征；表征 18 岁及以上中重度AD 受试者接受 amlitelimab 单药皮下注射给药的药代动力学（PK）；表征 18 岁及以上中重度AD 受试者接受 amlitelimab 单药皮下注射给药的免疫原性。

[Translation]

To demonstrate the efficacy of amlitelimab monotherapy administered subcutaneously (SC) compared with placebo in subjects 18 years and older with moderate to severe atopic dermatitis (AD); to evaluate the efficacy of amlitelimab monotherapy administered SC compared with placebo in subjects 18 years and older with moderate to severe AD; to evaluate the safety profile of amlitelimab monotherapy administered SC in subjects 18 years and older with moderate to severe AD; to characterize the pharmacokinetics (PK) of amlitelimab monotherapy administered SC in subjects 18 years and older with moderate to severe AD; and to characterize the immunogenicity of amlitelimab monotherapy administered SC in subjects 18 years and older with moderate to severe AD.

Start Date26 Apr 2024

Sponsor / Collaborator

Sanofi-Aventis Recherche et Développement SA

[+2]

CTR20241335 / RecruitingPhase 3

一项 III 期、随机、双盲、安慰剂对照、平行组、3 组、多国家、多中心研究，旨在评价以外用糖皮质激素为背景治疗的 18 岁及以上中重度特应性皮炎受试者皮下接受 amlitelimab 治疗的疗效和安全性。

[Translation] A phase III, randomized, double-blind, placebo-controlled, parallel-group, 3-arm, multinational, multicenter study was designed to evaluate the efficacy and safety of subcutaneous amlitelimab in subjects aged ≥18 years with moderate to severe atopic dermatitis treated with background topical corticosteroids.

主要：证明与安慰剂相比，以外用药为背景治疗的 18 岁及以上中重度特应性皮炎（AD）受试者接受 amlitelimab 皮下（SC）注射给药的疗效。次要：评估与安慰剂相比，以外用药为背景治疗的 18 岁及以上中重度 AD 受试者接受 amlitelimab 皮下给药的疗效。评估以外用药为背景治疗的 18 岁及以上中重度 AD 受试者接受 amlitelimab 皮下给药的安全性特征。表征以外用药为背景治疗的 18 岁及以上中重度 AD 受试者接受 amlitelimab 皮下给药的药代动力学（PK）。表征以外用药为背景治疗的 18 岁及以上中重度 AD 受试者接受 amlitelimab 皮下给药的免疫原性

[Translation]

Primary: To demonstrate the efficacy of amlitelimab administered subcutaneously (SC) compared to placebo in subjects 18 years of age and older with moderate to severe atopic dermatitis (AD) who were treated with background external medications. Secondary: To evaluate the efficacy of amlitelimab administered SC compared to placebo in subjects 18 years of age and older with moderate to severe AD who were treated with background external medications. To evaluate the safety profile of amlitelimab administered SC in subjects 18 years of age and older with moderate to severe AD who were treated with background external medications. To characterize the pharmacokinetics (PK) of amlitelimab administered SC in subjects 18 years of age and older with moderate to severe AD who were treated with background external medications. To characterize the immunogenicity of amlitelimab administered SC in subjects 18 years of age and older with moderate to severe AD who were treated with background external medications

Start Date24 Apr 2024

Sponsor / Collaborator

Genzyme Ireland Ltd.

[+2]

100 Clinical Results associated with Amlitelimab

100 Translational Medicine associated with Amlitelimab

100 Patents (Medical) associated with Amlitelimab

Literatures (Medical) associated with Amlitelimab

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 ; Quaratino, Sonia ; Cork, Michael J ; Wilson, Rosamund ; Stebegg, Marisa ; Bieber, Thomas ; O'Malley, John T

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.

25 Oct 2023·The British journal of dermatology

Safety and effectiveness of amlitelimab, a potential new treatment for atopic dermatitis: results of a clinical trial.

Article

01 May 2022·Clinical pharmacology and therapeuticsQ2 · MEDICINE

OX40L Inhibition Suppresses KLH‐driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof‐of‐Pharmacology for KY1005

Q2 · MEDICINE

Article

Author: Moerland, Matthijs ; Quaratino, Sonia ; Grievink, Hendrika W. ; Rissmann, Robert ; Yateman, Martin ; Gal, Pim ; Saghari, Mahdi ; Brennan, Nuala ; Porter‐Brown, Ben ; van Doorn, Martijn B. A. ; Klaassen, Erica S. ; Gilbert, Sally ; Bergmann, Kirsten R. ; Wilson, Rosamund ; Powell, John ; Burggraaf, Jacobus

The safety, tolerability, immunogenicity, and pharmacokinetic (PK) profile of an anti‐OX40L monoclonal antibody (KY1005, currently amlitelimab) were evaluated. Pharmacodynamic (PD) effects were explored using keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT) immunizations. Sixty‐four healthy male subjects (26.5 ± 6.0 years) were randomized to single doses of 0.006, 0.018, or 0.05 mg/kg, or multiple doses of 0.15, 0.45, 1.35, 4, or 12 mg/kg KY1005, or placebo (6:2). Serum KY1005 concentrations were measured. Antibody responses upon KLH and TT immunizations and skin response upon intradermal KLH administration were performed. PD data were analyzed using repeated measures analysis of covariances (ANCOVAs) and post hoc exposure‐response modeling. No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. A nonlinear increase in mean serum KY1005 concentrations was observed (median time to maximum concentration (Tmax) ~ 4 hours, geometric mean terminal half‐life (t½) ~ 24 days). Cutaneous blood perfusion (estimated difference (ED) −13.4 arbitrary unit (AU), 95% confidence interval (CI) −23.0 AU to −3.8 AU) and erythema quantified as average redness (ED −0.23 AU, 95% CI −0.35 AU to −0.11 AU) decreased after KY1005 treatment at doses of 0.45 mg/kg and above. Exposure‐response analysis displayed a statistically significant treatment effect on anti‐KLH antibody titers (IgG maximum effect (Emax) −0.58 AU, 95% CI −1.10 AU to −0.06 AU) and skin response (erythema Emax −0.20 AU, 95% CI −0.29 AU to −0.11 AU). Administration of KY1005 demonstrated an acceptable safety and tolerability profile and PK analyses displayed a nonlinear profile of KY1005. Despite the observed variability, skin challenge response after KY1005 treatment indicated pharmacological activity of KY1005. Therefore, KY1005 shows potential as a novel pharmacological treatment in immune‐mediated disorders.

News (Medical) associated with Amlitelimab

10 May 2024

·www.echemi.com

Top Scientist Resigns as Sanofi Reinvents Itself: A Shift Towards Immunology

In a significant move to establish its dominance in the field of immunology, pharmaceutical giant Sanofi has witnessed the departure of its Chief Scientific Officer and Research Director, Dr. Frank Nestle. The resignation of Dr. Nestle, announced on May 8, marks the highest-level exit since Sanofi initiated its global implementation of a streamlined research and development structure. This article delves into the company's strategic transformation, shedding light on its focus on immunology and the implications of Dr. Nestle's departure. Sanofi, a renowned player in the pharmaceutical industry, has been committed to creating its "immunology kingdom." CEO Paul Hudson had already hinted at a shift in the company's focus towards oncology in November 2023, outlining ambitious plans to increase the number of Phase 3 projects by 50% within two years, with a particular emphasis on immunology, neurology, and vaccines. As part of this initiative, Sanofi aimed to streamline its pipeline and allocate more funds to advance high-potential projects. Since the beginning of 2024, in alignment with the "Play to Win" program, Sanofi has relinquished several oncology projects acquired from Denali, Kymab, and Amunix, thereby reducing collaborations. Simultaneously, the company has initiated up to five rounds of layoffs, aiming to save up to €2 billion by the end of 2025. These measures reflect Sanofi's commitment to simplifying its research and development structure while optimizing resources for future endeavors. One notable development was the recent closure of a nearly $400 million acquisition of an NK cell therapy company, as announced during the update of the SAR445419 clinical trial information. SAR445419, an allogeneic NK cell therapy developed by Sanofi, was intended for the treatment of relapsed or refractory acute myeloid leukemia. However, due to Kiadis' withdrawal of funding, the SAR445419 Phase 1 study was prematurely terminated, resulting in the dissolution of the collaboration between Kiadis and Sanofi. Dr. Nestle joined Sanofi in September 2016, initially serving as the Global Head of Immunology and North America Chief Scientific Officer. Four years later, he was promoted to Global Head of Research and Chief Scientific Officer of the entire company. From April 2021 to October 2022, Dr. Nestle also chaired the board of Kiadis (now dissolved). With Kiadis' dissolution, Dr. Nestle's departure followed suit. Sanofi expressed its appreciation for Dr. Nestle's contributions in a statement to Fierce on May 8, stating that he played a key role in establishing a world-class research organization at Sanofi and remained an unwavering supporter of the company's "Play to Win" cultural transformation. The company acknowledged his exceptional leadership and dedication to advancing drug development for patients. Sanofi's relentless efforts to establish itself as an "immunology giant" involve capitalizing on the potential of its flagship immunoinflammatory agent, dupilumab. While fully exploring the potential of dupilumab, Sanofi also devotes resources to the development of successor products. The company's pipeline currently includes 34 projects related to immunology and inflammation, many of which hold tremendous potential to become groundbreaking therapies. Within the immunology pipeline, there are three potential Pipeline-In-a-Product (PIP) assets: amlitelimab, frexalimab, and the oral TNF blocker SAR441566. Each of these drugs possesses peak sales potential exceeding €5 billion. Sanofi's ongoing restructuring and streamlining efforts aim to generate the necessary funding for the development of a new generation of immunology products. Immunology occupies a crucial position in the company's strategic plans as it strives to establish itself as a leader in this therapeutic area. Recently, Sanofi further reduced its collaboration with IGMBiosciences, opting to prioritize antibodies targeting three immune and inflammatory (I&I) targets while abandoning three antibodies intended for oncology. Sanofi's transformation into an immunology-focused pharmaceutical powerhouse has witnessed the departure of Dr. Frank Nestle, its Chief Scientific Officer and Research Director. This strategic shift reflects the company's commitment to advancing innovative therapies in the field of immunology, with a particular emphasis on high-potential projects. As Sanofi strives to establish its "immunology kingdom," the departure of Dr. Nestle marks a significant milestone in the company's journey towards redefining its research and development landscape.

ImmunotherapyExecutive ChangePhase 1Cell TherapyAcquisition

25 Apr 2024

·firstwordpharma.com

All eyes on Dupixent decision in COPD as Sanofi suffers further pipeline setbacks

Sanofi said Thursday that Dupixent remains on track to record sales of around €13 billion this year after posting strong growth in the first quarter ahead of an expected expansion into chronic obstructive pulmonary disease. Revenue from Dupixent jumped 22.4% in the three-month period to €2.8 billion.The performance of Dupixent, along with Beyfortus (€182 million) and Altuviiio (€122 million), helped the company top expectations, with overall sales rising 2.4% to €10.5 billion, ahead of forecasts of €10.3 billion. However, net income plunged 43.2% to €1.1 billion.Sanofi reiterated its expectation that earnings this year will decrease by a low single-digit percentage at constant currencies. CEO Paul Hudson has braced investors for a period of slower growth over the next few years as the company directs resources into its drug-development, betting on 12 pipeline medicines including amlitelimab, frexalimab and tolebrutinib that it says have blockbuster potential.Pipeline setbacksHowever, Sanofi’s ambitions for frexalimab took a hit on Thursday after the company disclosed that development in Sjögren’s syndrome has been halted. Results from a Phase II trial failed to meet the “necessary efficacy outcomes” to continue to work in this indication, the drugmaker said, noting that Phase III studies of the anti-CD40L antibody in relapsing multiple sclerosis and secondary-progressive multiple sclerosis will continue, as well as mid-stage development in type 1 diabetes and systemic lupus erythematosus.Sanofi also disclosed Thursday that the Phase III AMETHIST trial of the GCS inhibitor venglustat for the treatment of GM2 gangliosidosis was discontinued based on “the absence of positive trends” for clinical endpoints. The company also confirmed the discontinuation of the RIPK1 inhibitor oditrasertib - announced by partner Denali Therapeutics in February – in amyotrophic lateral sclerosis.More to come.

Phase 2Phase 3Financial StatementClinical Trial FailureDrug Approval

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

100 Deals associated with Amlitelimab

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Dermatitis, Atopic	Phase 3	US	Sanofi	08 Nov 2023
Dermatitis, Atopic	Phase 3	CN	Sanofi	08 Nov 2023
Dermatitis, Atopic	Phase 3	AU	Sanofi	08 Nov 2023
Dermatitis, Atopic	Phase 3	BR	Genzyme Ireland Ltd.	08 Nov 2023
Dermatitis, Atopic	Phase 3	BR	Sanofi (China) Investment Co. Ltd.	08 Nov 2023
Dermatitis, Atopic	Phase 3	BR	Sanofi-Aventis Recherche et Développement SA	08 Nov 2023
Dermatitis, Atopic	Phase 3	CA	Sanofi	08 Nov 2023
Dermatitis, Atopic	Phase 3	CL	Sanofi	08 Nov 2023
Dermatitis, Atopic	Phase 3	FR	Genzyme Ireland Ltd.	08 Nov 2023
Dermatitis, Atopic	Phase 3	FR	Sanofi (China) Investment Co. Ltd.	08 Nov 2023

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05131477 (STREAM-AD, GlobeNewswire) Manual	Phase 2	Dermatitis, Atopic	390	amlitelimab (patients with continued treatment)	xwclrbbnrl(yqrxjsmdlv) = oilnjbabxt loydfazgzk (cylaqxzvfw ) View more	Positive	11 Mar 2024
				amlitelimab (patients withdrawn from treatment)	xwclrbbnrl(yqrxjsmdlv) = dfezuxzkty loydfazgzk (cylaqxzvfw ) View more
STREAM-AD (NEWS) Manual	Phase 2	Dermatitis, Atopic	390	amlitelimab	wxzipbvpab(lkyrhenksx) = llbpbufroq sfjkxrncfl (epabrlomsw ) View more	Positive	15 Oct 2023
				placebo	wxzipbvpab(lkyrhenksx) = uoigxuyiuv sfjkxrncfl (epabrlomsw ) View more
NCT03754309 (AAD2023)	Phase 2	Dermatitis, Atopic	89	Amlitelimab low-dose	rnopfrhvvl(gvendnuqrc) = 1 SAE (infected dermal cyst) was reported as possibly related; it resolved and the patient completed the study wcycxqpihm (isnlbwpljf ) View more	-	17 Mar 2023
				Amlitelimab high-dose
NCT03161288 (Pubmed \| Clin Pharmacol Ther)	Phase 1	-	64	KY1005	seypvnlzly(maqsrqzefd) = No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. ejptpnhkoe (chwunzgjqw ) View more	-	29 Jan 2022
				Placebo

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