Breakthrough Small Molecule Therapy Shows Positive Phase 3 Results and Nears Year-End Approval; GSK Acquires Potential Best-in-Class Liver Disease Treatment

May 15, 2025 07:49 CST Updated 07:49

GSK

Pharmaceutical R&D Manufacturer

Boston Pharmaceuticals

Biopharmaceutical Manufacturer

Septerna

Targeted Small Molecule Drug Developer

GSK Acquires Potential "Best-in-Class" Liver Disease Therapy

Today, GSK and Boston Pharmaceuticals announced an agreement whereby GSK will acquire Boston Pharmaceuticals' lead therapy, efimosfermin alfa. The therapy is currently in the Phase 3 preparation stage for the treatment and prevention ofProgression of Steatotic Liver Disease (SLD). According to the protocol,GSK will payBoston Pharmaceuticals received an upfront payment of $1.2 billion, with potential milestone payments totaling an additional $800 million.

Efimosfermin is an investigational, potential "best-in-class," once-monthly injectable fibroblast growth factor 21 (FGF21) analog.，Aiming to modulate key metabolic pathways to reduce liver fat, improve liver inflammation, and reverseMetabolic Dysfunction-Associated Steatohepatitis (MASH)The patient's liver fibrosis. The drug may be developed in the future for the treatment of alcoholic liver disease (ALD). Both MASH and ALD fall under SLD. Given the direct anti-fibrotic mechanism of action of efimosfermin and GSK's data insights based on human genetics and disease phenotype research,The drug has the potential to target later stages of SLD and may be used in combination with GSK's siRNA therapy, GSK'990, which is being developed for other subpopulations of SLD patients.

Data from a recent Phase 2 trial show,Efimosfermin can rapidly and significantly reverse liver fibrosis and halt its progression, with good tolerability.This trial aims to evaluate the efficacy and safety of monthly subcutaneous injections of efimosfermin in patients with moderate to severe (F2 or F3) MASH confirmed by biopsy. The data suggest that, compared with other treatments, efimosfermin may lead to greater fibrosis improvement, with its benefits expected to be independent of glucagon-like peptide-1 (GLP-1) therapy.In addition, efimosfermin may also reduce triglycerides and improve blood glucose control, which is particularly important for MASH patients who often have cardiometabolic comorbidities.Efimosfermin also has low immunogenicity and an extended half-life, offering the potential for a monthly dosing regimen and improved patient convenience.

SLD is a field with significant unmet medical needs, affecting approximately 5% of the global population, with limited treatment options for patients. SLD is characterized by liver fat accumulation (steatosis), accompanied by inflammation and fibrosis. Among them, ALD affects about 26 million patients worldwide and, together with MASH, is a leading cause of liver transplantation in the United States, placing a substantial burden on healthcare resources.

Novo Nordisk Reaches $2.2 Billion Small Molecule Therapy Collaboration

Septerna, Inc. and Novo Nordisk today announced a global exclusive collaboration and license agreement to jointly discover, develop, and commercialize oral small-molecule drugs for the treatment of obesity, type 2 diabetes, and other cardiometabolic diseases.The two parties will first launch four development projects to research and develop potential small molecule therapies targeting one or more specific G protein-coupled receptor (GPCR) targets, including GLP-1, GIP, and glucagon receptors.

GPCR is one of the largest and most diverse families of cell membrane receptors, with hundreds of different GPCRs regulating physiological processes in almost every organ system in the human body. Septerna, Inc., through its proprietary Native Complex Platform, is committed to fully unlocking the potential of GPCR therapies. The company focuses on developing a pipeline of orally administered small-molecule drugs across multiple therapeutic areas, initially concentrating on endocrine, immune and inflammatory, and metabolic diseases.

Under the terms of the agreement, Septerna is eligible to receive total payments of approximately $2.2 billion from Novo Nordisk, including upfront payments as well as research and development, development, and commercialization milestone payments.This includes upfront and near-term milestone payments of over 200 million US dollars. All R&D expenses for the co-development projects will be borne by Novo Nordisk. Both parties will jointly conduct research activities from the discovery stage to the selection of development candidates. Starting from the IND-enabling study phase, Novo Nordisk will take full responsibility for all development and commercialization efforts worldwide.

AbbVie Spends Billions on siRNA Therapy Development Collaboration

AbbVie and ADARx Pharmaceuticals announced today that they have reached a collaboration and license option agreement,Aiming to jointly develop small interfering RNA (siRNA) therapies applicable to multiple disease areas, including neuroscience, immunology, and oncology.

This strategic collaboration will fully leverage ADARx's expertise in RNA discovery and its proprietary siRNA technology, which has the potential to achieve durable and precise mRNA silencing. AbbVie will provide professional support in areas such as antibody engineering, antibody-drug conjugates, and tissue delivery strategies to assist ADARx in its drug discovery efforts.

According to the terms of the agreement,ADARx will receive a $335 million upfront payment and is eligible for billions of dollars in milestone payments.

Positive Phase 3 Results for Breakthrough Small Molecule Therapy! Approval for Market Launch Expected by End of Year

Recently, Cytokinetics announced the positive topline results of the MAPLE-HCM Phase 3 clinical trial. The analysis shows,Its research-stage small molecule inhibitor aFicamten Monotherapy for TreatmentIn patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), the efficacy is superior to existing standard therapies.The full results of the trial are expectedTo be announced at the upcoming medical conference.Aficamten is currently under review by the U.S. FDA, with a PDUFA date of December 26, 2025.

MAPLE-HCM is a multi-center, randomized, double-blind, active-controlled clinicalPhase 3 trial, inA Comparison of Aficamten Monotherapy with Existing Therapies in 175 Symptomatic Obstructive HCM PatientsEfficacy and Safety of Standard Treatment with the Beta-Blocker Metoprolol. The primary endpoint of the trial is the change in peak oxygen uptake (pVO2) from baseline to Week 24 as measured by cardiopulmonary exercise testing (CPET). Secondary endpoints include the change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores from baseline to Week 24, the proportion of patients with an improvement of ≥1 grade in New York Heart Association (NYHA) functional class, as well as left ventricular mass index (LVMI), left atrial volume index (LAVI), left ventricular outflow tract gradient (LVOT-G) post-Valsalva maneuver, andBiomarkers of Heart FailureChanges in NT-proBNP.

Analysis shows,MAPLE-HCM met the primary endpoint, showing a statistically significant advantage in the improvement of peak oxygen uptake from baseline to Week 24 with aficamten compared to the active control drug.In the MAPLE-HCM trial, aficamten also demonstrated a better safety and tolerability profile compared to the control group.

Aficamten is an investigational, potential "best-in-class" selective small molecule cardiac myosin inhibitor.Aficamten aims to reduce the number of active actin-myosin cross-bridges during each cardiac cycle, thereby inhibiting excessive myocardial contraction associated with HCM. In preclinical models, aficamten decreases myocardial contractility by directly binding to a unique, selective allosteric site on cardiac myosin, preventing myosin from entering the force-producing state.Aficamten has been granted by the U.S. FDA and China's National Medical Products Administration (NMPA)Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM.

References:

[1] GSK to acquire efimosfermin, a phase III-ready potential best-in-class specialty medicine to treat and prevent progression of steatotic liver disease (SLD). Retrieved May 14, 2025 from https://www.gsk.com/en-gb/media/press-releases/gsk-to-acquire-efimosfermin-a-phase-iii-ready-potential-best-in-class-specialty-medicine-to-treat-and-prevent-progression-of-steatotic-liver-disease-sld/

[2] Novo Nordisk A/S: Septerna and Novo Nordisk to collaborate on oral small molecule medicines for obesity and other cardiometabolic diseases. Retrieved May 14, 2025 from https://ir.septerna.com/news-releases/news-release-details/novo-nordisk-septerna-and-novo-nordisk-collaborate-oral-small

[3] AbbVie and ADARx Pharmaceuticals Announce Collaboration and License Option Agreement to Develop Next-Generation siRNA Therapies Across Multiple Therapeutic Areas. Retrieved May 14, 2025 from https://www.adarx.com/abbvie-and-adarx-pharmaceuticals-announce-collaboration-and-license-option-agreement-to-develop-next-generation-sirna-therapies-across-multiple-therapeutic-areas/

[4] Cytokinetics Announces Positive Topline Results From MAPLE-HCM. Retrieved May 14, 2015 from https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-positive-topline-results-maple-hcm

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