Delving into the Latest Updates on Astegolimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Astegolimab, AMG 282, ANTI-ST2

+ [6]

Target

IL-33R

Mechanism

IL-33R inhibitors(Interleukin-1 receptor-like 1 inhibitors)

Therapeutic Areas

Respiratory Diseases

Active Indication

Pulmonary Disease, Chronic Obstructive

Inactive Indication

Allergic asthmaAsthmaChronic rhinosinusitis with nasal polyps+ [3]

Originator Organization

Amgen, Inc.

Active Organization

Roche Holding AGHoffmann-La Roche, Inc.F. Hoffmann-La Roche Ltd.

+ [2]

Inactive Organization

Amgen, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 9469426H

Source: *****

Sequence Code 9470064L

Source: *****

Chronic obstructive pulmonary disease (COPD) is a main global epidemic increasing as population age and affecting approximately 10% of subjects over 45 years. COPD is a heterogeneous inflammatory disease with several endo-phenotypes and clinical presentations. Although neutrophilic inflammation is canonically considered a hallmark of COPD, eosinophilic inflammation can also be present in a subgroup of patients. Several other immune cells and cytokines play a key role in orchestrating and perpetuating the inflammatory pathways in COPD, making them attractive targets for treating this disorder. Recent studies have started to evaluate the possible role of type 2 (T2) inflammation and epithelial-derived alarmins (TSLP and IL-33) in COPD. Two phase III randomized clinical trials (RCTs) showed a modest reduction in exacerbations in COPD patients with eosinophilic phenotype treated with mepolizumab (anti-IL-5) or benralizumab (anti-IL-5Rα). A phase III RCT showed a 30% reduction in exacerbations in COPD patients with ≥ 300 eosinophils/μL treated with dupilumab (anti-IL-4Rα). These results suggest that blocking a single cytokine (e.g., IL-5) or its main target (i.e., IL-5Rα) is less promising than blocking a wider spectrum of cytokines (i.e., IL-4 and IL-13) in COPD. TSLP and IL-33 are upstream regulators of T2-high and T2-low immune responses in airway inflammation. Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD.

01 Nov 2023·Bioanalysis

Factors Contributing to the Nonlinear Pharmacokinetics of Astegolimab: A Close Examination of Potential Causes

Article

Author: Putnam, Wendy ; Zhang, Wenhui ; Fischer, Saloumeh K ; Dolton, Michael ; Sperinde, Gizette ; Mathews, Joel

Aim: This paper describes a case study of an antibody therapeutic targeting a membrane-bound receptor, also present in systemic circulation, as a soluble receptor. During phase I studies of astegolimab, nonlinear pharmacokinetics (PKs) were observed. We investigated the potential contribution of antidrug antibodies, target-mediated drug disposition and assay format. Materials & methods: A more target-tolerant assay was developed, and a subset of phase I samples were evaluated in both free and total PK assay formats. Results & conclusion: Our results demonstrate that there were two main contributors to PK nonlinearity: soluble target interference in the free PK assay, in addition to target-mediated drug disposition. Antidrug antibody status did not significantly impact PK.

01 Jan 2023·Critical care medicine

Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial*

Article

Author: McKinnell, James A. ; Mohan, Divya ; Cheung, Dorothy ; Chen, Hubert ; Pappu, Rajita ; Peck, Melicent C. ; Yang, Xiaoying ; Brooks, Logan ; Theess, Wiebke ; Rosenberger, Carrie M. ; Kalil, Andre C. ; Waters, Michael ; Wang, Yehong ; Zhang, Wenhui ; Martin, Greg S. ; Lekkerkerker, Annemarie N. ; Staton, Tracy ; Buchman, Timothy G. ; Galanter, Joshua

OBJECTIVES::

Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS. This study aimed to evaluate safety and efficacy of astegolimab, a human immunoglobulin G2 monoclonal antibody that selectively inhibits the IL-33 receptor, ST2, or efmarodocokin alfa, a human IL-22 fusion protein that activates IL-22 signaling, for treatment of severe COVID-19 pneumonia.

DESIGN::

Phase 2, double-blind, placebo-controlled study (COVID-astegolimab-IL).

SETTING::

Hospitals.

PATIENTS::

Hospitalized adults with severe COVID-19 pneumonia.

INTERVENTIONS::

Patients were randomized to receive IV astegolimab, efmarodocokin alfa, or placebo, plus standard of care. The primary endpoint was time to recovery, defined as time to a score of 1 or 2 on a 7-category ordinal scale by day 28.

MEASUREMENTS AND MAIN RESULTS::

The study randomized 396 patients. Median time to recovery was 11 days (hazard ratio [HR], 1.01 d; p = 0.93) and 10 days (HR, 1.15 d; p = 0.38) for astegolimab and efmarodocokin alfa, respectively, versus 10 days for placebo. Key secondary endpoints (improved recovery, mortality, or prevention of worsening) showed no treatment benefits. No new safety signals were observed and adverse events were similar across treatment arms. Biomarkers demonstrated that both drugs were pharmacologically active.

CONCLUSIONS::

Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia.

2

News (Medical) associated with Astegolimab

27 Sep 2024

·endpts.com

FDA approves Dupixent in COPD, opening ‘next chapter’ for Sanofi and Regeneron’s bestseller

The biggest drug driving Sanofi’s and Regeneron’s businesses is about to get a bit bigger. On Friday, the FDA approved Dupixent as an add-on to typical inhaled medicines for patients with inadequately controlled COPD, or chronic obstructive pulmonary disease, and high levels of a type of white blood cell called eosinophils. China regulators also granted a similar approval in COPD on Friday . The drugmakers estimate 300,000 people in the US fall under that description, representing a lucrative new market for the megablockbuster as well as a new treatment option for the hard-to-treat lung condition. “The latest approval in COPD represents an incredible next chapter for Dupixent, giving those with COPD a novel option that has demonstrated the unprecedented ability to help patients experience fewer attacks, while also helping them breathe better and improve quality of life in Phase 3 trials,” George Yancopoulos, Regeneron’s chief scientific officer, said in a statement. Since it was first approved in 2017, Dupixent has exploded into a business-defining drug for Regeneron and Sanofi, which co-developed the antibody that blocks IL-4 and IL-13. The drug has won approvals for a range of diseases driven by allergy or inflammation, such as eczema and asthma. Dupixent brought in about $6.6 billion in sales for the first half of 2024. In a research note to investors in August, Evercore ISI analyst Cory Kasimov forecast that Dupixent will generate $14.5 billion in sales for the year. The COPD market is key in continuing Dupixent’s relentless growth. In a note earlier this month, Jefferies analyst Akash Tewari said he expects $3.8 billion in peak sales of Dupixent in COPD, above a Wall Street consensus of $3.3 billion. In a pair of Phase 3 studies, COPD patients treated with Dupixent experienced roughly one-third fewer COPD attacks than a placebo group over the course of a year. The studies only enrolled patients with blood eosinophil levels of at least 300 cells per microliter. Dupixent is now the first biologic approved to treat COPD, but rival drugs may not be far behind. Earlier this month, GSK said its IL-5-targeting antibody Nucala succeeded in a Phase 3 COPD study . AstraZeneca and Amgen are planning a Phase 3 program for Tezspire in COPD after proof-of-concept results in a Phase 2a study were presented this May . Roche expects Phase 3 results next year for an antibody called astegolimab. Sanofi and Regeneron are also testing a combination of Dupixent and an IL-33 antibody called itepekimab to treat a broader swath of COPD patients. They expect Phase 3 results in the second half of 2025.

Drug ApprovalPhase 3Phase 2Clinical Result

21 Apr 2021

·www.biospace.com

Roche Quietly Pulls Two Phase II COVID-19 Studies in Q1

Taljat David/Shutterstock Roche has culled two more Phase II COVID-19 programs. The Swiss pharma giant quietly announced the cuts this morning in a breakdown of its first quarterly financial report. Roche said it removed a monoclonal antibody licensed from Amgen, as well as an IL-22 inhibitor, both of which were being assessed against COVID-19-related pneumonia. Roche pulled a mid-stage study of its monoclonal antibody astegolimab (RG6149), which it had previously licensed from Amgen. The drug binds IL-33 to ST2. This is the second Phase II stud with astegolimab the company has terminated. Earlier this year, Roche canceled a mid-stage study of the asset in asthma. Roche also terminated a Phase II study with RG7880 (efmarodocokin alfa) in COVID-19. Like astegolimab, Roche hoped efmarodocokin alfa, which binds to IL-22, would be effective in preventing disease worsening of COVID-19-related pneumonia. In its quarterly report, Roche did not provide additional details of why those two programs were pulled. Despite the failures of those COVID assets, Roche did make headway against the global pandemic during the first three months of the year, particularly in its diagnostics division. Roche said its SARS-CoV-2 Rapid Antigen Test Nasal, which can quickly identify people with the highest risk to be infectious, received CE mark and special approvals for self-testing in several European countries. Also, Roche said its research-use cobas SARS-CoV-2 Variant Set 1 Test was launched in the quarter to help monitor coronavirus mutations across the globe. Also in the first quarter, Roche boosted its diagnostics business with the $1.8 billion acquisition of GenMark Diagnostics, one of the first companies to receive Emergency Use Authorization from the U.S. Food and Drug Administration for its ePlex SARS-CoV-2 Test. That test will complement Roche’s own COVID-19 tests, including the Elecsys IL-6 test, which measures levels of IL-6 (interleukin-6), as well as its Elecsys Anti-SARS-CoV-2 antibody test. On the therapeutics side, Roche highlighted its partnership with Regeneron. The company said the antibody combination of casirivimab/imdevimab is now benefitting patients in an increasing number of countries, incl. the United States, Germany, Italy, France and Switzerland. The antibody combination continues to demonstrate positive clinical results. In Phase III studies in the prevention of COVID-19, the casirivimab/imdevimab cocktail reduced symptomatic infections by 81% and reduced hospitalization or death by 70%. Roche said it will continued to ramp-up of production capacity for COVID-19-related diagnostics and medicines. “In 2021, Roche remains strongly committed to the fight against COVID-19. The uptake of our recently introduced diagnostic tests and medicines remains strong, while we continue to see the expected impact from biosimilars on sales of our established medicines,” Roche Chief Executive Officer Severin Schwan said in a statement. In addition to the two COVID-19 programs, Roche also said it pulled a Phase III cancer study with Tecentriq, as well as two asthma programs and two oncology programs, all in Phase I testing. Earlier this year, Roche announced the termination of other programs in its pipeline. In addition to astegolimab in asthma, Roche also canceled multiple mid- and late-stage programs in oncology, ulcerative colitis and autism spectrum disorder. While Roche may have pulled some studies with Tecentriq this quarter, Roche did see its checkpoint inhibitor hit the mark as a potential treatment for early-stage lung cancer. The company also posted positive results for faricimab in ophthalmology.

AntibodyBiosimilarEmergency Use AuthorizationFinancial StatementAcquisition

100 Deals associated with Astegolimab

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16386

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Disease, Chronic Obstructive	Phase 3	JP	Hoffmann-La Roche, Inc.	29 Dec 2022
Pulmonary Disease, Chronic Obstructive	Phase 3	PR	Hoffmann-La Roche, Inc.	29 Dec 2022
COVID-19	Phase 2	US	Genentech, Inc.	02 Jun 2020
COVID-19	Phase 2	BR	Genentech, Inc.	02 Jun 2020
COVID-19	Phase 2	MX	Genentech, Inc.	02 Jun 2020
COVID-19	Phase 2	ES	Genentech, Inc.	02 Jun 2020
Moderate Atopic Dermatitis	Phase 2	US	Genentech, Inc.	06 Feb 2019
Moderate Atopic Dermatitis	Phase 2	DE	Genentech, Inc.	06 Feb 2019
Moderate Atopic Dermatitis	Phase 2	PL	Genentech, Inc.	06 Feb 2019
Severe Atopic Dermatitis	Phase 2	US	Genentech, Inc.	06 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03747575 (CTgov)	Phase 2	Moderate Atopic Dermatitis \| Severe Atopic Dermatitis	65	MSTT1041A (Treatment)	lspnjflnmd(bgoeuthtmc) = fjzgbpfojw zvnfaaiznz (daxfftwphd, oiehwwxixm - vrfraayjig) View more	-	06 May 2023
				Placebo (Placebo)	lspnjflnmd(bgoeuthtmc) = fahdabauxb zvnfaaiznz (daxfftwphd, wzpepqanov - rzsctzqzuj) View more
Pubmed	Phase 2	COVID-19	396	Astegolimab	qjqhjamqyt(enyrvshngn) = povtpprfur olejbkkgac (uvxyegvlba )	Negative	01 Jan 2023
				Efmarodocokin alfa	qjqhjamqyt(enyrvshngn) = vpzbssvmsk olejbkkgac (uvxyegvlba )
NCT02918019 (CTgov)	Phase 2	Asthma	517	Placebo	pbqqqtzhze(laixjyztwe) = rcweekanoy hmzzgobgto (vewcdukcsf, vnwijcwztk - wetoxhuafo) View more	-	28 Dec 2022
NCT03747575 (Pubmed) Manual	Phase 2	Dermatitis, Atopic	65	Astegolimab	spadsahqfu(tmhplvlfcm) = ceuugesfno zxrjdfamyu (bqwluqorxl )	Negative	27 Aug 2022
				Placebo	spadsahqfu(tmhplvlfcm) = qxsuwuwucu zxrjdfamyu (bqwluqorxl )
NCT03615040 (COPD-ST2OP, CTgov)	Phase 2	Pulmonary Disease, Chronic Obstructive	81	MSTT1041A (Anti-ST2)	dbpqaocurq(hwyuluwtfc) = bpzkyaqqcl lezkdzqljq (bikrdmxxtd, gfhgannmad - rbqcdebeeh) View more	-	24 May 2022
				Placebo (Placebo)	dbpqaocurq(hwyuluwtfc) = ssezglnwij lezkdzqljq (bikrdmxxtd, nhrtduhgoi - tpmocngiol) View more
NCT03615040 (COPD-ST2OP, Pubmed \| Lancet Respir Med) Manual	Phase 2	Pulmonary Disease, Chronic Obstructive	-	Astegolimab	mslrcbzbvy(uxmrijzsib) = similar between group rhkljsxypb (pmvbqtyobw ) View more	Positive	24 Mar 2022
				Placebo
COPD-ST2OP (ERS2021)	Phase 2	Pulmonary Disease, Chronic Obstructive blood eosinophil count	-	Astegolimab 490mg	wvopckmycs(ecaqbprlds) = ylveiryzec yojiiewynm (vxdorlcqex, -10 to 90)	Negative	05 Sep 2021