RedHill Advances RHB-102 for GLP-1 Therapy Side Effects as Market Faces $35 Billion Loss Risk
核心洞察
RedHill Biopharma is developing RHB-102, a once-daily oral ondansetron formulation, to address gastrointestinal side effects associated with GLP-1/GIP receptor (搜索) agonist therapies like Ozempic and Mounjaro.
The company plans to initiate a Phase 2 proof-of-concept study for GLP-1-associated GI side effects, leveraging positive Phase 3 results in gastroenteritis (搜索) and Phase 2 results in IBS-D.
Up to 50% of patients discontinue GLP-1 therapies within three months due to GI side effects, potentially reducing the GLP-1 market value by $35 billion by 2030 according to Goldman Sachs (搜索).
RedHill Biopharma announced significant development progress for RHB-102 (Bekinda®), positioning the investigational drug to address a critical challenge facing the multi-billion-dollar GLP-1 receptor (搜索) agonist market. The company is advancing RHB-102 as a once-daily oral therapy to manage gastrointestinal side effects associated with popular diabetes (搜索) and weight loss medications including Ozempic®/Wegovy® and Mounjaro®/Zepbound®.
Addressing a Major Market Challenge
More than 2% of Americans currently take GLP-1 receptor (搜索) agonists, but estimates suggest up to 50% of patients discontinue these therapies within three months. According to Goldman Sachs (搜索) analysis, GI side-effect-driven discontinuation could reduce forecasted GLP-1 market valuations by an estimated $35 billion by 2030.
Dr. Terry Plasse, RedHill's Medical Director, explained the therapeutic rationale: "RHB-102's once-daily oral profile may improve titration success, which we believe may result in reaching and maintaining optimal GLP-1 receptor (搜索) agonist doses. The overall aim is to help patients navigate the 'danger zone' early months of therapy, where GI-side effects, like nausea (搜索), vomiting (搜索) and diarrhea (搜索), are most prevalent."
Clinical Development Strategy
RedHill has designed a Phase 2 proof-of-concept study for RHB-102 in GLP-1/GIP receptor (搜索) agonist therapy-associated GI side effects, planned to commence as early as possible this year. The development will proceed through the accelerated FDA 505(b)(2) regulatory pathway.
RHB-102 is a proprietary, patent-protected bimodal extended-release oral tablet formulation of ondansetron, a 5-HT3 antagonist. The drug's bimodal design provides both immediate and extended-release properties in a once-daily dosing regimen.
Strong Clinical Foundation
The development program benefits from an extensive body of supporting clinical data. RHB-102 demonstrated positive results in a U.S. Phase 3 GUARD study for gastroenteritis (搜索), which met its primary endpoint and was published in JAMA Network Open. Additionally, positive Phase 2 results for diarrhea (搜索)-predominant irritable bowel syndrome (搜索) (IBS-D) were published in The American Journal of Gastroenterology.
Dr. Plasse emphasized the de-risked nature of the program: "RedHill believes that RHB-102 is largely de-risked and supported by prior positive U.S. Phase 3 results in gastroenteritis (搜索)/gastritis, positive U.S. Phase 2 results for IBS-D, and decades of ondansetron clinical use with more than 22 million U.S. emergency room prescriptions annually."
Multiple Indication Strategy
Beyond GLP-1-associated side effects, RedHill is pursuing potential FDA approval for RHB-102 in oncology support applications. If approved, RHB-102 could become the first oral 24-hour extended-release ondansetron antiemetic drug for treating chemotherapy/radiotherapy-induced nausea (搜索) and vomiting (搜索) (CINV/RINV). The company has also expanded RHB-102's intellectual property coverage for relevant indications, including GLP-1-associated nausea and vomiting.
The comprehensive development strategy targets multiple GI indications including acute gastroenteritis (搜索) and gastritis, IBS-D, and post-operative nausea (搜索) and vomiting (搜索) (PONV), in addition to the GLP-1-associated applications.
Partnership and Commercialization
RHB-102 is partnered with Hyloris Pharma (搜索) for worldwide development and commercialization outside North America. Dr. Plasse noted that the patent-protected formulation provides "a compelling partnership choice with published late-stage data, standard manufacturing, low cost of goods sold and multiple potential indications."
The clinical data supporting potential FDA approval will include results from the positive comparative pharmacokinetic clinical study as part of the oncology support program, plus any additional outcomes from the planned Phase 2 proof-of-concept study in GLP-1/GIP receptor (搜索) agonist therapy-associated GI side effects.