[Translation] A single-dose clinical study evaluating the safety, tolerability, and pharmacokinetics of Sotatercept (MK-7962) in healthy Chinese subjects

1）在中国健康受试者中评价0.3 mg/kg和0.7 mg/kg sotatercept单次SC给药后sotatercept的安全性；2）在中国健康受试者中评价0.3 mg/kg和0.7 mg/kg sotatercept单次SC给药后sotatercept的PK。

[Translation]

1) To evaluate the safety of sotatercept after a single SC administration of 0.3 mg/kg and 0.7 mg/kg sotatercept in healthy Chinese subjects; 2) To evaluate the PK of sotatercept after a single SC administration of 0.3 mg/kg and 0.7 mg/kg sotatercept in healthy Chinese subjects.

Start Date22 Nov 2023

Sponsor / Collaborator

MSD R&D (China) Co. Ltd.

[+2]

NCT05818137 / Active, not recruitingPhase 3

A Phase 3 Non-randomized, Non-controlled, Open Label Clinical Study to Evaluate the Efficacy and Safety of MK-7962 (Sotatercept) add-on to Background Therapy in Japanese Participants With Pulmonary Arterial Hypertension (PAH)

This local Phase 3 study is planned to confirm the efficacy and safety in Japanese PAH participants. The primary population of this study is Japanese PAH participants with World Health Organization Functional Class (WHO FC) II or III while the study includes PAH participants with WHO FC I or IV as other populations. There are no hypotheses for this study.

Start Date10 May 2023

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Sotatercept

100 Translational Medicine associated with Sotatercept

100 Patents (Medical) associated with Sotatercept

119

Literatures (Medical) associated with Sotatercept

01 Jan 2024·Annals of internal medicine

Recurrent Gastrointestinal Bleeding in a Patient With Pulmonary Arterial Hypertension Treated With Sotatercept

Letter

Author: Schoenberg, Noah C ; Farber, Harrison W ; Feuerstein, Joseph D ; Fricker, Zachary P ; Hakim, Aaron

01 Jan 2024·Advances in therapy

Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH)

Article

Author: Nourhussein, Iman ; Bernotas, David ; Pausch, Christine ; Martinez, Eliana C ; Klok, Rogier ; McLaughlin, Vallerie ; Lautsch, Dominik ; Chevure, Jestinah ; Hoeper, Marius M ; Alsumali, Adnan ; Liu, Rongzhe ; De Oliveira Pena, Janethe

INTRODUCTION:

Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT. BGT was comprised of mono-, double-, or triple-PAH targeted therapy. Building on STELLAR findings, we employed a population health model to assess the potential long-term clinical impact of sotatercept.

METHODS:

Based on the well-established ESC/ERS 4-strata risk assessment approach, we developed a six-state Markov-type model (low risk, intermediate-low risk, intermediate-high risk, high risk, lung/heart-lung transplant, and death) to compare the clinical outcomes of sotatercept plus BGT versus BGT alone over a lifetime horizon. State-transition probabilities were obtained from STELLAR. Risk stratum-adjusted mortality and lung/heart-lung transplant probabilities were based on COMPERA PAH registry data, and the post-transplant mortality probability was obtained from existing literature. Model outcomes were discounted at 3% annually. Sensitivity analyses were conducted to examine model robustness.

RESULTS:

In the base case, sotatercept plus BGT was associated with longer life expectancy from model baseline (16.5 vs 5.1 years) versus BGT alone, leading to 11.5 years gained per patient. Compared with BGT alone, sotatercept plus BGT was further associated with a gain in infused prostacyclin-free life years per patient, along with 683 PAH hospitalizations and 4 lung/heart-lung transplant avoided per 1000 patients.

CONCLUSIONS:

According to this model, adding sotatercept to BGT increased life expectancy by roughly threefold among patients with PAH while reducing utilization of infused prostacyclin, PAH hospitalizations, and lung/heart-lung transplants. Real-world data are needed to confirm these findings.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier, NCT04576988 (STELLAR).

01 Jan 2024·Journal of Cancer

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo

Article

Author: Zarogoulidis, Paul ; Matthaios, Dimitris ; Petridis, Dimitris ; Charalampidis, Charalampos ; Sardeli, Chrysanthi ; Nikolaou, Christina ; Petanidis, Savvas ; Hohenforst-Schmidt, Wolfgang ; Huang, Haidong ; Bai, Chong ; Pitsiou, Georgia ; Kougas, Nikos ; Porpodis, Konstantinos ; Kosmidis, Christoforos ; Papadopoulos, Vasilis ; Oikonomou, Panagoula ; Perdikouri, Eleni-Isidora

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5μm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

News (Medical) associated with Sotatercept

09 May 2024

·www.globenewswire.com

Inhibikase Therapeutics Announces Final Pre-IND Meeting Outcomes for IkT-001Pro as a Treatment for Pulmonary Arterial Hypertension

- FDA indicated IkT-001Pro can be considered a New Molecular Entity and is eligible for exclusivity designations in Pulmonary Arterial Hypertension – BOSTON and ATLANTA, May 09, 2024 (GLOBE NEWSWIRE) -- Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (“Inhibikase” or “Company”), a clinical-stage pharmaceutical company developing protein kinase inhibitor therapeutics to modify the course of Parkinson's disease, Parkinson's-related disorders and other diseases of the Abelson Tyrosine Kinases, today announced that the Company has received final meeting minutes from its recent pre-IND meeting with the Division of Cardiology and Nephrology of the U.S. Food and Drug Administration (FDA) for IkT-001Pro (“Pro”) as a candidate treatment for Pulmonary Arterial Hypertension (PAH). Following review of the final meeting minutes, Inhibikase is preparing the Investigational New Drug (IND) application. “Following our pre-IND discussion with the FDA related to the chemical entity status and path to approval for Pro as a treatment for Pulmonary Arterial Hypertension, the FDA confirmed in final meeting minutes that Pro would be considered a New Molecular Entity (NME) in PAH,” said Dr. Milton Werner, President and Chief Executive Officer of Inhibikase. “This designation opens the path to patent and NME exclusivity for IkT-001Pro even though the FDA agreed that the 505(b)(2) path is appropriate for approval. If approved, IkT-001Pro could be a branded product with all the value drivers of a novel treatment for an indication of high unmet medical need. PAH is a rapidly progressing, often fatal disease affecting primarily women between the ages of 30 and 60. There are several products on the market that address symptoms of the disease, but only one disease-modifying therapy has been approved to date. In previous clinical trial work, imatinib, the active ingredient in Pro, demonstrated that it could be disease-modifying for PAH. We believe that Pro has the potential to be a safer and better tolerated therapeutic option for imatinib treatment and are actively pursuing partnership discussions to advance Pro into clinical development.” In the final minutes from the pre-IND meeting, the FDA agreed that Inhibikase had built a bridge between imatinib’s use in blood and gastrointestinal cancers and PAH and supported the Company’s Phase 2/3 design as the initial clinical pursuit. The FDA requested the Company complete a pre-clinical cell culture-based study of the hERG ion channel to compare Pro to imatinib as Imatinib has previously been linked with certain cardiovascular abnormalities. The Company intends to complete this 7-day experiment prior to an IND submission. In parallel, the Company has initiated discussions with potential strategic partners in order to advance the development of Pro for Pulmonary Arterial Hypertension. Pulmonary Arterial Hypertension is a rare disease of the pulmonary microvasculature. PAH can arise spontaneously, or can be caused by genetic mutations, drugs or environmental toxins. PAH is also associated with connective tissue disease (CTD), congenital heart disease and HIV infection. Most treatments for PAH attempt to address symptoms of this progressive disorder, but the recent approval of Winrevair® highlights that disease-modification is possible. There are approximately 30,000 cases of PAH in the U.S. The global PAH market size was valued at $7.66 billion in 2023 and is estimated to grow at a compound annual growth rate of 5.4% between 2024 to 2030. About Inhibikase (www.inhibikase.com) Inhibikase Therapeutics, Inc. (Nasdaq: IKT) is a clinical-stage pharmaceutical company developing therapeutics for Parkinson's disease and related disorders. Inhibikase's multi-therapeutic pipeline has a primary focus on neurodegeneration and its lead program risvodetinib, an Abelson Tyrosine Kinase (c-Abl) inhibitor, targets the treatment of Parkinson's disease inside and outside the brain as well as other diseases that arise from Abelson Tyrosine Kinases. Its multi-therapeutic pipeline is pursuing Parkinson's-related disorders of the brain and GI tract, orphan indications related to Parkinson's disease such as Multiple System Atrophy, and drug delivery technologies for kinase inhibitors such as IkT-001Pro, a prodrug of the anticancer agent imatinib mesylate that the Company believes will provide a better patient experience with fewer on-dosing side-effects. The Company's RAMP™ medicinal chemistry program has identified several follow-on compounds to risvodetinib that could potentially be applied to other cognitive and motor function diseases of the brain. Inhibikase is headquartered in Atlanta, Georgia with offices in Lexington, Massachusetts. Social Media DisclaimerInvestors and others should note that the Company announces material financial information to investors using its investor relations website, press releases, SEC filings and public conference calls and webcasts. The Company intends to also use X, Facebook, LinkedIn and YouTube as a means of disclosing information about the Company, its services and other matters and for complying with its disclosure obligations under Regulation FD. Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking terminology such as "believes," "expects," "may," "will," "should," "anticipates," "plans," or similar expressions or the negative of these terms and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Inhibikase's current expectations and assumptions. Such statements are subject to certain risks and uncertainties, which could cause Inhibikase's actual results to differ materially from those anticipated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include our ability to enroll and complete the 201 Trial evaluating risvodetinib in untreated Parkinson’s disease, to successfully apply for and obtain FDA approval for IkT-001Pro in blood and stomach cancers or other indications, to successfully conduct clinical trials that are statistically significant and whether results from our animal studies may be replicated in humans, as well as such other factors that are included in our periodic reports on Form 10-K and Form 10-Q that we file with the U.S. Securities and Exchange Commission. Any forward-looking statement in this release speaks only as of the date of this release. Inhibikase undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. Contacts: Company Contact:Milton H. Werner, PhDPresident & CEO678-392-3419info@inhibikase.com Investor Relations:Alex LoboStern Investor Relations, Inc.alex.lobo@sternir.com

Drug ApprovalFast TrackINDClinical Study

06 May 2024

·firstwordpharma.com

Chiesi bets up to $486M on Gossamer pulmonary hypertension drug

Italian pharma Chiesi Farmaceutici has agreed to pay Gossamer Bio up to $486 million in milestones and other payments to jointly develop and commercialise seralutinib (GB002), the latter's experimental inhaled drug for pulmonary hypertension.Upfront, Gossamer will receive $160 million from Chiesi as a development reimbursement payment. The biotech is also eligible for up to $146 million more if seralutinib hits regulatory milestones and $180 million tied to sales milestones.The PDGFRα/β, CSF1R, and c-KIT inhibitor is designed to be delivered via dry powder inhaler. Gossamer has been developing the drug for pulmonary arterial hypertension (PAH), where a registrational Phase III trial called PROSERA is already underway. A top-line readout is expected in the fourth quarter of 2025, according to H. C. Wainwright analysts.Expansion to PH-ILDUnder the deal, Gossamer and Chiesi now plan to launch a second Phase III trial of seralutinib in mid-2025 focused on pulmonary hypertension associated with interstitial lung disease (PH-ILD). Giuseppe Accogli, chief executive at Chiesi Group, said seralutinib could be a "paradigm shifting therapy" for both indications.Data from the Phase II TORREY study, recently published in the Lancet Respiratory Medicine, showed a significant improvement with seralutinib compared to placebo on the primary endpoint of reduction in pulmonary vascular resistance (PVR) at 24 weeks, and other key measures such as right heart structure and function.Under the agreed terms, Chiesi has exclusive rights to commercialise seralutinib outside the US and will pay Gossamer an "escalating mid-to-high teens royalty" on net sales in those territories. In the US, the companies will split commercial profits and losses evenly, with Gossamer leading commercialisation, including contributing 50% of commercial activities and booking of sales for both PAH and PH-ILD. Chiesi will lead US commercialisation for additional indications.The deal comes shortly after Merck & Co. won an FDA approval for its drug Winrevair (sotatercept-csrk) in March, making it the first activin signaling inhibitor for PAH cleared in the US. For more, see Spotlight On: Winrevair approval could help Merck & Co. overcome its Keytruda issues.

Phase 3Phase 2Clinical ResultDrug ApprovalLicense out/in

06 May 2024

·www.biopharmadive.com

Gossamer sells rights to drug it hopes can rival a new Merck therapy

Gossamer Bio has sold rights to an experimental drug that could rival a new medicine from Merck & Co., in a deal at least one analyst believes bodes well for the company.On Monday, Gossamer and the Italy-based Chiesi Farmaceutici announced a collaboration and licensing agreement to develop and eventually sell the drug, which is called seralutinib. Gossamer has been testing seralutinib as a potential treatment for an uncommon disease known, in short, as PAH, and is currently recruiting patients in a late-stage clinical trial meant to serve as the basis for approval applications.PAH, or pulmonary arterial hypertension, is a form of high blood pressure in the lungs. The pressure makes the heart work harder to pump blood, over time causing the organ to weaken or even fail. The Food and Drug Administration has approved several blood vessel-widening medicines that help alleviate the symptoms of PAH, and more recently cleared a first-of-its-kind therapy from Merck & Co.Unlike other treatments, Mercks Winrevair inhibits a protein that thickens the walls of blood vessels. The therapy is injected every three weeks, and is seen as a valuable product by both Wall Street and Merck, which acquired it through an $11.5 billion buyout of Acceleron Pharma in 2021. Analysts have predicted Winrevair could generate annual sales anywhere between $1 billion to $8 billion at its peak.Gossamer believes theres still room in the market for its drug, as it also works differently than available treatment options and comes as an inhaled powder. Results from a smaller PAH study encouraged the company to advance seralutinib into that late-stage trial, titled Prosera, which will enroll 350 participants and complete by late 2025.While Gossamer remains confident in its drug, company investors have questioned the strength of those earlier trial results and whether seralutinib can truly compete with Winrevair. Shares of Gossamer lost three-quarters of their value in late 2022, when findings from the smaller study were announced. As of Monday morning, they traded at about 75 cents apiece.Joseph Schwartz, an analyst at investment firm Leerink Partners, wrote in a note to clients that the new deal with Chiesi could address many of the concerns investors have with Gossamer. Chief among those concerns, according to Schwartz, is the companys ability to enroll and fund Prosera.The collaboration bodes well for Gossamer based on the amount of diligence that typically precedes a collaboration, the analyst wrote.Per deal terms, Gossamer will continue leading the development of seralutinib in PAH as well as another, related indication the companies are interested in: pulmonary hypertension associated with interstitial lung disease. Though Gossamer and Chiesi will evenly split development costs, the former is responsible for financing Prosera.In the U.S., the partners plan to evenly share commercial profits and losses. Gossamer will helm commercialization efforts for those two diseases, while Chiesi will take the lead for any additional indications.Chiesi will also have the exclusive right to commercialize seralutinib outside of the U.S. Gossamer will get mid-to-high teens royalties on net sales. Chiesi has agreed to pay Gossamer $160 million as a development reimbursement, and may shell out up to $326 million more, provided certain regulatory and sales milestones are achieved. '

License out/inAcquisitionClinical StudyDrug Approval

100 Deals associated with Sotatercept

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
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
Depressive Disorder	NDA/BLA	CA	Merck Canada, Inc.	-
Depressive Disorder	NDA/BLA	-	Merck Canada, Inc.	-
Anemia	Phase 3	US	Celgene Corp.	-
Myelofibrosis	Phase 2	US	National Cancer Institute	21 Feb 2013
Myelofibrosis	Phase 2	US	The University of Texas MD Anderson Cancer Center	21 Feb 2013
Primary Myelofibrosis	Phase 2	US	-	19 Feb 2013
Chronic Myelomonocytic Leukemia	Phase 2	US	Celgene Corp.	28 Nov 2012
Chronic Myelomonocytic Leukemia	Phase 2	US	Merck Sharp & Dohme 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

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03738150 (SPECTRA Phase 2b Study, Pubmed)	Phase 2	Pulmonary Arterial Hypertension	21	Sotatercept	fbrzwtthtk(xyuiocuesw) = gcfqkmewcm dtxlgmweyw (donwuzglng, 27.72 - 177.76)	Positive	04 Apr 2024
NCT04576988 (STELLAR, FDA_CDER) Manual	Phase 3	Pulmonary Arterial Hypertension	323	WINREVAIR	yceznkyzre(kyasuvuzbp) = ilznuqjhbb cmavsstkha (bsnjgdjazp ) View more	Positive	26 Mar 2024
				Placebo	ovwfhvobxd(ugvdizfmux) = jfegxngarq wjfayngwyr (bzdtruhyop ) View more
NCT01146574 (CTgov)	Phase 2	Anemia	50	placebo (Part 1-Placebo)	hskxbaqjnv(mchxcbeqyz) = vvnlmqhzkm pjxczedpjw (fkfjxvzpdx, gxzvwgwwed - jjurcwqxtt) View more	-	01 Mar 2024
				1-ACE-011 (Part 1-ACE-011 0.1 mg/kg)	gftqaeuibj(qgxylszqhv) = dllkyrqfih cmjqniqudk (dfeoubtwul, uskdfippnm - qczmzbgjpm) View more
NCT01190644 (CTgov)	Phase 2	Solid tumor	5	Sotatercept	wommzwubmm(qznhzeorif) = djmhylsyvu ghiolqkbsi (dhfpghiyrj, pswtcihxvu - butooipqct) View more	-	29 Nov 2023
NCT01284348 (CTgov)	Phase 2	Anemia	26	Sotatercept 15 mg (Sotatercept 15 mg)	ijltfrvkxj(brhabojblx) = osaiexxxjk ucefkoqhfg (cjchyivjfm, lkdovutjar - eysghlmzrd) View more	-	31 Oct 2023
				Sotatercept 30 mg (Sotatercept 30 mg)	ijltfrvkxj(brhabojblx) = gkpozojani ucefkoqhfg (cjchyivjfm, yleqfnxcof - votjelmkme) View more
NCT00931606 (MK-7962-012 \| 7962-012, CTgov)	Phase 2	Anemia	30	Sotatercept (Sotatercept 0.1 mg/kg)	noztwgvdaw(aqebfvgemx) = qeuyewbrme mdyjlzozvp (lyyjegsapd, nukkztskjb - ecibcansjv) View more	-	13 Sep 2023
				Sotatercept (Sotatercept 0.3 mg/kg)	noztwgvdaw(aqebfvgemx) = zhoxhdneao mdyjlzozvp (lyyjegsapd, ubrraqbmtq - jyabsoiccc) View more
STELLAR (Literature) Manual	Phase 3	Pulmonary Arterial Hypertension	-	sotatercept	cbwrgejrux(ugzxktumai) = gybpmgttjn xcychzemqp (wexyaqvqty ) View more	Positive	11 Sep 2023
				placebo	-
NCT04576988 (STELLAR \| 7962-003, CTgov)	Phase 3	Pulmonary Arterial Hypertension	324	Sotatercept+Background PAH Therapy (Sotatercept Plus Background PAH Therapy)	prabnostek(fglcxuzumh) = ngxonuksvi eavjyrsjwc (xrnqbxncty, zdidljbdni - cpdofllqps)	-	23 Aug 2023
				Background PAH Therapy (Placebo Plus Background PAH Therapy)	prabnostek(fglcxuzumh) = etyatmjglm eavjyrsjwc (xrnqbxncty, gxlhqhramu - shqcdrwstz)
NCT01571635 (CTgov)	Phase 2	Beta-Thalassemia	46	Sotatercept (Dose Level 1a: 0.1 mg/kg)	rvokodywuc(rdgtzyrhyn) = kylifgpfsm zmeqssdoht (chlcfwincq, gvmsvoarcp - ecebfrtvub) View more	-	18 Jun 2023
				Sotatercept (Dose Level 1b: 0.3 mg/kg)	rvokodywuc(rdgtzyrhyn) = wydbuwfmki zmeqssdoht (chlcfwincq, zbzwrcqjlr - kiugngplyn) View more
NCT01712308 (CTgov)	Phase 2	Anemia \| Myelofibrosis \| Primary Myelofibrosis	56	Sotatercept (Treatment Monotherapy (Sotatercept))	mswveovakb(nfsjbxzuyd) = wpldscfklk dpunqxvszk (mxttyeomdi, oqypkrreuq - kiidgmuiqr) View more	-	06 Jun 2023
				Sotatercept+Ruxolitinib (Treatment Combination (Ruxolitinib + Sotatercept))	mswveovakb(nfsjbxzuyd) = hejaclohuz dpunqxvszk (mxttyeomdi, xnjacprtgm - cgiirgonpm) View more

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