Delving into the Latest Updates on Sotatercept with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

ACTRIIA-Fc, Sotatercept (USAN/INN), SOTATERCEPT-CSRK

+ [6]

Target

ACVR2A x activin receptor

Mechanism

ACVR2A modulators(activin A receptor type 2A modulators), activin receptor antagonists(Activin receptor antagonists)

Therapeutic Areas

Nervous System DiseasesRespiratory DiseasesOther Diseases+ [5]

Active Indication

Depressive DisorderPulmonary Arterial HypertensionAnemia+ [3]

Inactive Indication

Anemia, Diamond-BlackfanBeta-ThalassemiaBladder Cancer+ [9]

Originator Organization

Acceleron Pharma, Inc.

Active Organization

Merck Sharp & Dohme BV

Indiana University

Acceleron Pharma, Inc.

+ [6]

Inactive Organization

Northwell Health, Inc.

Drug Highest PhaseApproved

First Approval Date

US (26 Mar 2024),

Pulmonary Arterial Hypertension

RegulationPriority Review (US), Orphan Drug (EU), PRIME (EU), Orphan Drug (AU), Priority Review (AU), Breakthrough Therapy (US), Orphan Drug (US)

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Gene Sequence

Sequence Code 156629

Source: *****

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodelling resulting in elevated pressures in the pulmonary artery (PA). This elevated pressure ultimately leads to fulminant right heart failure. Current therapeutic options are limited and are centred around vasodilatory medications such as phosphodiesterase-5 inhibitors and prostacyclin. While these medications allow for the widening of blood vessels that are narrowed due to remodelling, they have no effect on the remodelling itself.
Sotatercept is a novel medication which targets the BMPR2/TGF-β pathway and restore a pro- and anti- proliferative balance to ultimately counteract vascular remodelling. Recent phase 2 and 3 trials showed that treatment with sotatercept led to lower resistance and pressure in the pulmonary vasculature and improved exercise tolerance. However, these results were not coupled with an increase in cardiac output, a change that is seen with other PAH-medications with a primarily vasodilatory effect. These results suggest that cardiac work is reduced and cardiac efficiency is improved in patients being treated with sotatercept, in contrast with conventional PAH therapies. This is a potentially beneficial effect that may result in improved disease control in the long-term. Our study aims to explore the effect of sotatercept on cardiac work and function. We hypothesize that the effects of sotatercept are more beneficial for cardiac function than that of traditional PAH medications.
All participants included in the trial will undergo a screening visit in which it will be checked that all inclusion criteria and no exclusion criteria are met. The screening visit involves a physical exam, blood draw, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast to assess fibrosis.
Upon inclusion, all participants will receive a subcutaneous injection of sotatercept starting at a dose of 0.3 mg/kg. Participants will return to the hospital every three weeks for a blood draw, physical examination and an adverse event review. If the laboratory values (specifically haemoglobin and platelet counts) stay stable after the first dose, the dosage will be escalated to 0.7 mg/kg. The dose will not be escalated beyond 0.7 mg/kg.
After 24 weeks of receiving sotatercept, there will be an end of treatment visit including a physical exam, 6-minute walk test, right heart catheterization (RHC) and cardiac magnetic resonance imaging (cMRI) with contrast material.

Start Date01 Jan 2025

Sponsor / Collaborator

Stichting Onderzoek Cancer Center Amsterdam

NCT06664801 / RecruitingPhase 2

A Phase 2, Multicenter, Single-blinded, Randomized Study to Evaluate the Pharmacokinetics and Safety of Sotatercept (MK-7962) Administered Using Either a Weight-based or Weight-banded Approach in Participants With Pulmonary Arterial Hypertension (PAH) on Standard of Care

Researchers are looking for other ways to treat people with PAH. In PAH, the blood vessels in the lungs become thick and narrow, which makes it harder for blood to flow to the lungs.
The goal of the study is to learn:
* What happens to different doses of sotatercept in a person's body over time when it is given using weight-banded doses compared to weight-based doses. There may be differences in how the medicine works with the new dosing method (weight-banded dosing) being studied in this trial.
* About the safety of sotatercept and if people tolerate it

Start Date14 Nov 2024

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT06409026 / RecruitingPhase 4IIT

Effect of Sotatercept on Central Cardiopulmonary Performance and Peripheral Oxygen Transport During Exercise in Pulmonary Arterial Hypertension

The purpose of this study is to see if the drug sotatercept given for 36 weeks improves the functioning of the heart and improves quality of life.

Start Date05 Jul 2024

Sponsor / Collaborator

Mayo Clinic

100 Clinical Results associated with Sotatercept

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100 Translational Medicine associated with Sotatercept

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100 Patents (Medical) associated with Sotatercept

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147

Literatures (Medical) associated with Sotatercept

01 Jan 2025·JOURNAL OF HEART AND LUNG TRANSPLANTATION

A new day has come: Sotatercept for the treatment of pulmonary arterial hypertension

Review

Author: Moles, Victor M ; Moles, Victor M. ; Cascino, Thomas M ; McLaughlin, Vallerie V ; Sahay, Sandeep ; Cascino, Thomas M. ; McLaughlin, Vallerie V.

Despite increasing therapeutic options and evolving treatment strategies, including targeting 3 therapeutic pathways, in the management of pulmonary arterial hypertension (PAH), morbidity and mortality have remained unacceptably high. Sotatercept is a first-in-class, novel activin signaling inhibitor approved for treating PAH based on evolving efficacy and safety evidence. This state-of-the-art review summarizes the current understanding of the mechanism of action, the impact on outcomes that improve how patients feel, function, and survive, and the safety and adverse event profile to inform readers of this breakthrough novel therapy.

01 Dec 2024·VASCULAR PHARMACOLOGY

Sotatercept: New drug on the horizon of pulmonary hypertension

Review

Author: Madonna, Rosalinda ; Biondi, Filippo

Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway and the bone morphogenic protein (BMP) antiproliferative pathway in the pulmonary arterial cirulation. Sotatercept recently received approval in the USA and in Europe for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. Nevertheless, several studies are ongoing to investigate the potential adverse reactions of the drug especially at the haematological level. We provide an overview of the clinical and preclinical evidence of the targeting the activing pathway through sotatercept on the treatment of PAH. We also discuss what other possibilities there are for the application of sotatercept in the setting of pulmonary hypertension other than PAH Group 1.

01 Dec 2024·JOURNAL OF HEART AND LUNG TRANSPLANTATION

Efficacy and Safety of Sotatercept Across Ranges of Cardiac Index in Patients with Pulmonary Arterial Hypertension: A Pooled Analysis of PULSAR and STELLAR

Article

Author: Badesch, David B ; Souza, Rogerio ; Gomberg-Maitland, Mardi ; Grünig, Ekkehard ; Olsson, Karen M ; Hoeper, Marius M ; Ardeschir Ghofrani, H ; Kopeć, Grzegorz ; Waxman, Aaron B ; Perchenet, Loïc ; McLaughlin, Vallerie V ; Meyer, Gisela ; Cornell, Alexandra G ; Pena, Janethe de Oliveira ; Preston, Ioana R ; Strait, James ; Rosenkranz, Stephan ; Johnson-Levonas, Amy O ; Gibbs, J Simon R ; Humbert, Marc ; Xing, Aiwen

BACKGROUND:

This analysis compared effects of the activin signaling inhibitor, sotatercept, across pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI).

METHODS:

Pooled data from PULSAR (N=106; NCT03496207) and STELLAR (N=323; NCT04576988) were analyzed using two different CI thresholds, < and ≥ 2.0 L/min/m² or 2.5 L/min/m². Median differences in change from baseline at week 24 were evaluated using Hodges-Lehmann (HL) estimator and mean differences by least squares (LS), with 95% confidence intervals and p-values; p=0.05 was significant. Categorial endpoints and time-to-clinical worsening were analyzed by Cochran-Mantel-Haenszel and Cox model (hazard ratio (HR), respectively, without multiplicity adjustment.

RESULTS:

Of 429 participants, 51 and 378 had CI <2.0 L/min/m² and ≥ 2.0 L/min/m², respectively, whereas 179 and 250 had CI <2.5 L/min/m² and ≥ 2.5 L/min/m², respectively. Across all CI subgroups, sotatercept vs placebo significantly improved median 6-minute walk distance (range: 33.9 to 63.7 m: p<0.001), pulmonary vascular resistance (range: -202.8 to -395.4 dyn•s•cm^-5; p≤0.002), and N-terminal pro-B-type natriuretic peptide (range: -317.3 to -1041.2 pg/mL; p<0.001). LS means showed reductions in pulmonary and right atrial pressures, decreased right ventricular size and enhanced tricuspid annular plane systolic excursion/ systolic pulmonary artery pressure in all subgroups. Sotatercept significantly delayed time to first occurrence of death or a worsening event in the subset of participants with CI ≥2.5 (HR 0.12; p<0.001), ≥2.0 (HR 0.13; p<0.001), and <2.5 (HR 0.21; p<0.001) L/min/m². Improvements in World Health Organization functional class (all p<0.050) and European Society of Cardiology/European Respiratory Society risk score (all p<0.001) were seen within each subgroup.

CONCLUSIONS:

Efficacy and safety were consistent across baseline CI subgroups, supporting use of sotatercept in PAH patients irrespective of baseline cardiac hemodynamics.

122

News (Medical) associated with Sotatercept

12 Dec 2024

·www.biopharmadive.com

Keros shares collapse on ‘unanticipated’ setback for lung disease drug

Dive Brief:Keros Therapeutics shares plummeted Thursday after the company said researchers conducting a Phase 2 study have stopped giving patients the two highest doses of its lead experimental drug because of reports of excess fluid buildup in the pericardial sac around the heart.The Tropos trial is designed to test three doses of Keros cibotercept in patients with pulmonary arterial hypertension who are already receiving other therapy for the condition. After reviewing the reports of pericardial effusion, company executives and independent monitors decided the trial could go on for patients receiving the lowest dose, but halted research of higher doses.This is an unanticipated observation in this trial, CEO Jasbir Seehra told analysts and investors on a conference call. We will be doing further work to try to understand it, but it is unanticipated based upon all the biology that we understand from preclinical and healthy volunteer studies.Dive Insight:Investors had viewed cibotercept as a potential improvement on Mercks Winrevair, which analysts view as a potential $5 billion-a-year seller. Part of the case for the Keros drug was the possibility for better safety than Winrevair as well as a chance at superior efficacy at higher doses.Though Keros will continue to test a lower dose in the Tropos study, investors clearly have lost faith in the medicine. Keros shares tumbled 77% early Thursday, wiping out more than $2 billion of market value.We believe the clinical setback will make it difficult to regain investor interest in cibotercept, which was the companys lead program and main value driver, William Blair analyst Matt Phipps wrote in a note to investors. While the lower dose could show a favorable benefit/risk profile, we believe it will take more data to convince investors and physicians and ultimately to compete with Merck, he said.Before the latest setback, Keros had been one of the most successful initial public offerings of the last four years, with its shares surging more than 300% from the companys IPO price of $16, according to BioPharma Dive data. The stock traded at about $16 early Thursday after closing at almost $69 on Wednesday.Keros had benefited in part from the success of Merck, which won approval for Winrevair in March and released more positive data in November. Mercks drug is transformative for patients, and the case for buying Keros stock was that the company had an even better option in development, Cantor Fitzgerald analyst Prakhar Agrawal wrote when he initiated coverage of Keros in October.Though cibotercept is the companys lead drug, Keros does have others in its pipeline. An experimental blood disease drug called elritercept recently drew the eye of Takeda, which agreed to pay $200 million for rights outside of China, Hong Kong and Macau. '

Phase 2IPO

11 Dec 2024

·pmlive.com

Merck and Ridgeback initiate phase 3 study of COVID-19 oral antiviral in high-risk adults

Merck & Co – known as MSD outside of the US and Canada – and Ridgeback Biotherapeutics have initiated a late-stage study to evaluate an investigational oral antiviral COVID-19 drug in adults who are at high risk for disease progression. The phase 3 MOVe-NOW trial of orally-administered Lagevrio (molnupiravir) is enrolling patients who have tested positive for SARS-CoV-2 infection, have had COVID-19 symptoms for four days or less, and are not hospitalised. Patients eligible for the study will also not be able to receive nirmatrelvir/ritonavir due to drug-drug interactions, allergy, previous adverse effects, or inaccessibility, and will be randomised to receive either Lagevrio 800mg or placebo orally every 12 hours for five days. Lagevrio is already available in the US under emergency use authorisation to treat adults with mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19 and for whom alternative treatment options are not accessible or clinically appropriate. MOVe-NOW will use a different formulation of the drug that includes two smaller 400mg tablets per dose instead of the currently available four 200mg capsules per dose. Paula Annunziato, senior vice president, infectious diseases and vaccines, global clinical development, Merck Research Laboratories, said: “COVID-19 remains a leading cause of hospitalisation and death around the world, and further studying Lagevrio may provide important insights into how it may be used to help prevent severe outcomes in the current COVID-19 environment. “We continue to believe Lagevrio may be an important option for people with risk factors like older age, multiple comorbidities, and immunocompromising conditions, who are more likely to advance to severe COVID-19, and for whom other antiviral treatments may not be appropriate because of the potential for drug-drug interactions.” The announcement comes just days after Merck shared positive top-line results from a late-stage trial of its pulmonary arterial hypertension therapy Winrevair (sotatercept-csrk). The phase 3 ZENITH study met its primary endpoint, with Winrevair demonstrating a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to placebo in adults with World Health Organization functional classes three or four at high risk of mortality.

Phase 3Clinical ResultEmergency Use Authorization

04 Dec 2024

·www.echemi.com

Pharmaceutical Giants Surge: Merck Revenue Soars 18%! Eli Lilly Reports $31.5 Billion in Q1-3 Revenue

Merck's revenue grew by 18% in the third quarter, with projected annual sales of Keytruda exceeding $29 billion, potentially reaching $30 billion. The 15-valent pneumonia vaccine generated $239 million in revenue, a 13% increase. The 21-valent pneumonia vaccine performed well in the market. However, sales of the 9-valent HPV vaccine in China declined by 10%. Sales of the cardiovascular drug Winrevair reached $149 million, with approximately 1,700 new patients in the third quarter. Despite a downward adjustment in annual revenue guidance, the strong performance of Keytruda and investment in R&D provide support for Merck's future growth. Eli Lilly reported $11.44 billion in revenue for the third quarter, a 20% increase, with a net profit of $970 million. Total revenue for the first three quarters reached $31.5 billion, a 27% increase, with net profit at $6.18 billion. Sales of innovative drugs were strong, particularly tirzepatide, which achieved $11 billion in sales during the first three quarters. Eli Lilly's launch of innovative drugs in cardiovascular, immunology, and oncology fields supports its revenue growth. Other multinational pharmaceutical companies, such as Novartis, Sanofi, and AstraZeneca, also achieved double-digit growth due to the release of innovative drugs, market expansion, and cost control. Johnson & Johnson, AbbVie, and BMS experienced slight growth in the third quarter, maintaining their positions in the top ten. GSK dropped out of the top ten due to declining performance. Johnson & Johnson reported $22.5 billion in revenue, a 5.2% increase, with pharmaceutical business growth of 4.9% and medical device business growth of 5.8%. Sales of the BCMA CAR-T therapy in collaboration with Legend Biotech reached $629 million, an increase of 84.3%. Johnson & Johnson faced challenges, with self-immunity business growth slowing to 1% and ustekinumab sales declining by 1.2%. However, the oncology business grew by 17.2%, becoming a new driver of performance. AbbVie reported $41.232 billion in revenue for the first three quarters, an increase of about 3%. The patent cliff effect of Humira caused a 37.2% decline in sales, but strong sales of Skyrizi and Rinvoq supported performance. GSK's revenue for the third quarter was £8.012 billion, a decrease of 1.6%. The vaccine sector performed poorly, with sales of Arexvy and Shingrix declining. Specialty pharmaceuticals grew by 19%, and oncology grew by 94%. GSK plans to increase investment in specialty pharmaceuticals, seeking to revive its vaccine sector and expand its partnership network. The global pharmaceutical industry shows diversified performance, with concerns arising from the underperformance of some companies. Pharmaceutical companies need to strengthen innovation, international cooperation, and marketing to ensure long-term stable development. Pfizer, Johnson & Johnson, and AbbVie performed outstandingly, while companies like GSK provide insights for adjustment and transformation.

VaccineFinancial StatementDrug Approval

100 Deals associated with Sotatercept

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External Link

KEGG	Wiki	ATC	Drug Bank
D09670	-	-	DB12118

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder	CA	Merck Canada, Inc.	01 Aug 2024
Pulmonary Arterial Hypertension	US	Merck Sharp & Dohme LLC	26 Mar 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anemia	Phase 3	US	Celgene Corp.	-
Myelofibrosis	Phase 2	US	The University of Texas MD Anderson Cancer Center	21 Feb 2013
Primary Myelofibrosis	Phase 2	US	The University of Texas MD Anderson Cancer Center	21 Feb 2013
Chronic Myelomonocytic Leukemia	Phase 2	US	Merck Sharp & Dohme Corp.	28 Nov 2012
Chronic Myelomonocytic Leukemia	Phase 2	US	Celgene Corp.	28 Nov 2012
Chronic Myelomonocytic Leukemia	Phase 2	FR	Celgene Corp.	28 Nov 2012
Chronic Myelomonocytic Leukemia	Phase 2	FR	Merck Sharp & Dohme Corp.	28 Nov 2012
Myelodysplastic Syndromes	Phase 2	US	Merck Sharp & Dohme Corp.	28 Nov 2012
Myelodysplastic Syndromes	Phase 2	US	Celgene Corp.	28 Nov 2012
Myelodysplastic Syndromes	Phase 2	FR	Merck Sharp & Dohme Corp.	28 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04896008 (ZENITH, Company_Website) Manual	Phase 3	Pulmonary Arterial Hypertension	-	sotatercept-csrk	cljgrfwnpt(gdlfkwrczu) = ZENITH met its primary endpoint of time to first morbidity or mortality event (all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours). pswtdzxuyj (hbcohvelwp ) Met	Positive	26 Nov 2024
				Placebo
NCT01999582 (CTgov)	Phase 2	Anemia	50	Sotatercept (Group 1: Sotatercept 0.1 mg/kg Intravenous (IV) Injection)	elcvuvueqy(ckkidsozae) = kikaboogko ekeeeejvvx (aubbvgopyw, keunpxnlpy - rcngrnexwt) View more	-	24 Jun 2024
				Sotatercept (Group 1: Sotatercept 0.13 mg/kg Subcutaneous (SC) Injection)	elcvuvueqy(ckkidsozae) = saxzeryrov ekeeeejvvx (aubbvgopyw, lojskxwpwt - tzutmpfaan) View more
STELLAR (ATS2024)	Not Applicable	Pulmonary Arterial Hypertension	-	Immediate access to sotatercept	bthpqxzplx(wilsqrpbiu) = bcmsmkgfzx veaelvocvi (xqzuuqcwry )	Positive	19 May 2024
				Delayed access to sotatercept	bthpqxzplx(wilsqrpbiu) = osorzhehxu veaelvocvi (xqzuuqcwry )
PULSAR (ATS2024)	Phase 2	Pulmonary Arterial Hypertension BMPR2 \| N-terminal pro B-type natriuretic peptide (NT-proBNP) \| BMPR2 mRNA	106	Sotatercept 0.3 mg/kg	egromlejei(ihlshbdjcl) = zmnryrnzom jzqlhozrtg (hmxtqptsfw )	Positive	19 May 2024
				Sotatercept 0.7 mg/kg	egromlejei(ihlshbdjcl) = wtfzwfusfw jzqlhozrtg (hmxtqptsfw )
NCT03738150 (SPECTRA, Pubmed) Manual	Phase 2	Pulmonary Arterial Hypertension	21	Sotatercept	zisamvhoqf(genrhackjn) = oobraqmuwi ebkdbjoqkn (lgtbnutpyp, 27.72 - 177.76)	Positive	04 Apr 2024
NCT04576988 (STELLAR, FDA_CDER) Manual	Phase 3	Pulmonary Arterial Hypertension	323	WINREVAIR	vmqlchxthp(halwwnfdwq) = cdasgajabl kbvnxajkyc (lohipzkiup ) View more	Positive	26 Mar 2024
				Placebo	cjjjjdqmcv(wnifangurm) = emlkbvnwxe twdiutrbex (mduxwijxbd ) View more
NCT01146574 (CTgov)	Phase 2	Anemia	50	placebo (Part 1-Placebo)	weeggmxejf(yryurangij) = oiletvvosc rjzqtjeavk (sqmwtgdenr, hpgepyhgvz - kypkqhhpbo) View more	-	01 Mar 2024
				1-ACE-011 (Part 1-ACE-011 0.1 mg/kg)	oumtlkekwr(imelqbvypb) = orhiyzhdmx ijqtdpvgwa (mkjhrpmcng, rvdyfsrosr - tveciphrmf) View more
NCT04576988 (STELLAR, Pubmed \| Adv Ther)	Phase 3	Pulmonary Arterial Hypertension	-	Sotatercept plus background therapy (BGT)	iazelhicru(qeyvpsabvb) = eybtigbepd fbpevwclbh (cptsqvilck ) View more	Positive	01 Jan 2024
				Placebo plus background therapy (BGT)	iazelhicru(qeyvpsabvb) = bezzbxbjox fbpevwclbh (cptsqvilck ) View more
NCT01190644 (CTgov)	Phase 2	Solid tumor	5	Sotatercept	olrzkqtqjw(ktdcqbxopq) = naskkvohlq tocguqrkhj (gnoshcfifp, kujumhotog - zoukmkwwnu) View more	-	29 Nov 2023
NCT01284348 (CTgov)	Phase 2	Anemia	26	Sotatercept 15 mg (Sotatercept 15 mg)	oxphxsqgvl(gojbpyyogj) = fxnzkyymhh qljmsjocax (qmesltqifq, veomjqqrpo - ozrbkbbwoo) View more	-	31 Oct 2023
				Sotatercept 30 mg (Sotatercept 30 mg)	oxphxsqgvl(gojbpyyogj) = nsovhjtsbl qljmsjocax (qmesltqifq, qrmosrhdpt - xvmwqbrixa) View more