A Prospective Single-Arm Exploratory Trial of Intestinal Microecology and Motility Modulation for Preventing Anastomotic Leakage After Surgery for Left-Sided Colon or Rectal Cancer

Start Date01 Oct 2026

Sponsor / Collaborator

West China Hospital

NCT06424522

/ RecruitingNot ApplicableIIT

Low Anterior Resection Syndrome: Retrograde Enema Program vs Medical Management

This clinical trial studies if a bowel management program with a retrograde rectal enema (RRE) for the treatment of low anterior resection syndrome (LARS) in rectal cancer patients is better than medical management alone. Rectal cancer treatment can include a procedure where part of the rectum with cancer is removed and the remaining part of the rectum is reconnected to the colon, this is called a low anterior resection of the rectum. LARS is a common condition that can develop after undergoing a low anterior resection of the rectum. LARS consists of any change in how the body performs defecation, the discharge of feces from the body, after undergoing a resection procedure. Patients with LARS may experience fecal urgency, incontinence, increased frequency, constipation, feelings of incomplete bowel movement, or bowel emptying difficulties. Patients may experience individual symptoms of LARS or a combination of them. A bowel management program assists patient's with identifying a specific bowel management regimen that works best for managing symptoms of LARS. A RRE consists of inserting a catheter through the anus into the rectum. The RRE is designed to assist fecal emptying. Medical management of LARS can include the use of fiber, loperamide hydrochloride, or pelvic floor physical therapy. Fiber may help relieve constipation, feelings of incomplete bowel movement, or bowel emptying difficulties. Loperamide hydrocholoride may help lessen fecal urgency, incontinence, or increased frequency. Pelvic floor physical therapy may help restore strength in the rectum possibly helping to improve symptoms of LARS. Participating in a bowel management program with a RRE may be more effective in treating LARS than medical management alone.

Start Date15 Aug 2026

Sponsor / Collaborator

Ohio State University Comprehensive Cancer Center

NCT07426822

/ RecruitingPhase 2IIT

A Phase II Trial to Improve Safety of Capivasertib for HR+/HER2- Metastatic Breast Cancer

This is a randomized, multicenter, phase II clinical trial evaluating prophylactic strategies to mitigate common toxicities associated with capivasertib in combination with fulvestrant in participants with hormone receptor-positive (HR+), HER2-negative advanced breast cancer who are eligible for this treatment regimen.

Start Date15 Aug 2026

Sponsor / Collaborator

Yale University

[+1]

100 Clinical Results associated with Loperamide Hydrochloride

100 Translational Medicine associated with Loperamide Hydrochloride

100 Patents (Medical) associated with Loperamide Hydrochloride

2,934

Literatures (Medical) associated with Loperamide Hydrochloride

01 Jan 2027·JOURNAL OF ETHNOPHARMACOLOGY

Mechanistic insights into Cistanche deserticola aqueous extract in alleviating functional constipation: Integration of gut microbiota remodeling and focal adhesion-associated mucosal repair

Article

Author: Hu, Jiangshan ; Wang, Yifei ; Tang, Meng ; Liu, Haibin ; Liu, Lu ; Ma, Xuran ; Gao, Yan ; Tian, Xiao ; Lv, Jing

ETHNOPHARMACOLOGICAL RELEVANCE:

Cistanche deserticola Ma (Orobanchaceae), a widely used botanical drug in Traditional Chinese Medicine, is traditionally utilized to moisten the intestines and relieve constipation, particularly for senile and deficiency-induced constipation.

AIM OF THE STUDY:

To evaluate the restorative effects of C. deserticola (CD) aqueous extract on functional constipation (FC) and elucidate its multi-omic mechanisms mediated by the gut microbiota-short-chain fatty acid (SCFA)-host axis.

MATERIALS AND METHODS:

The CD extract was phytochemically characterized via UPLC-Q-TOF-MS/MS. Loperamide induced FC mice were treated with physiologically relevant doses of CD extract (369 and 615 mg/kg/day). Efficacy was assessed via phenotypic, biochemical, and histopathological evaluations. Mechanisms were explored integrating 16S rRNA sequencing, targeted SCFA metabolomics, and colonic transcriptomics. Fecal microbiota transplantation (FMT) was conducted to verify microbiota dependency. Key signaling networks were validated using Western blotting and immunofluorescence.

RESULTS:

CD administration significantly accelerated intestinal transit, repaired mucosal barriers, restored gastrointestinal hormones, and mitigated oxidative and inflammatory stress. Microbiome profiling demonstrated CD reversed dysbiosis by enriching beneficial SCFA-producers (e.g., Lachnospiraceae NK4A136 group), correspondingly elevating colonic propionate and butyrate. FMT confirmed these therapeutic effects were microbiota-driven. Transcriptomic and molecular validations revealed that CD-mediated microecological restoration reactivated the Integrin αL/p-FAK/Filamin C mechanotransduction cascade and PDGFC/SGK1 signaling pathways, thereby promoting focal adhesion and structural mucosal repair.

CONCLUSIONS:

CD alleviates FC by concurrently remodeling the gut microbiota, enhancing SCFA production, and reactivating colonic mechanotransductive tissue repair networks. This provides a robust scientific rationale for its traditional ethnopharmacological use in constipation management.

01 Jan 2027·JOURNAL OF ETHNOPHARMACOLOGY

Ethnopharmacological validation of Capparis spinosa L. in gastrointestinal and respiratory disorders: Evidence from in vitro, in vivo, and in silico models

Article

Author: Rana, Samia Latif ; Aleem, Ambreen

ETHNOPHARMACOLOGICAL RELEVANCE:

Capparis spinosa L. is traditionally used in Pakistan to treat gastrointestinal and respiratory ailments, yet its multi-target pharmacological mechanisms remain poorly understood.

AIM OF THE STUDY:

To evaluate the traditional use of Capparis spinosa L. in asthma, diarrhea, and spasm using integrated in vitro, in vivo, and in silico approaches.

METHODOLOGY:

Hydroethanolic extract of C. spinosa L. (Cap.Cr) was analyzed by LC ESI-MS/MS. Antispasmodic and bronchodilator activities of Cap.Cr and its fractions (Ethyl acetate, n-hexane, aqueous) were assessed using isolated jejunal segments from rabbit intestine, trachea, and urinary bladder. Antidiarrheal potential was assessed in mice using castor oil-induced diarrhea, enteropooling, and intestinal transit models. Rat fecal samples were analyzed via qRT-PCR to assess the presence of Firmicutes, Lactobacillus, and V2. Molecular docking explored interactions with calcium channels and muscarinic receptors.

RESULTS:

LC ESI-MS/MS study identified 26 bioactive flavonoids and alkaloids. In vitro, Cap.Cr and its fractions relaxed the contractions provoked by high K⁺ and carbachol (CCh) across all tissues. The extracts shifted the Ca²⁺ and carbachol cumulative response curves (CRCs), suggesting dicyclomine-like dual Ca²⁺ antagonistic and antimuscarinic mechanism. In vivo, C. spinosa (50-200 mg/kg) significantly (p < 0.05) lessened diarrheal episodes, fluid accumulation, and intestinal transit showing efficacy comparable to loperamide and atropine. Microbiota analysis indicated an increase in Firmicutes and Lactobacillus levels by C. spinosa. In silico docking suggested high binding affinities for muscarinic receptors (M₃) and voltage-gated Ca²⁺ channels.

CONCLUSION:

C. spinosa L. exerts potent antispasmodic, bronchodilator, and antidiarrheal effects and may involve Ca²⁺ channel blockade and muscarinic antagonism, demonstrating pharmacological justification for its traditional use in gut and airway dysfunctions.

01 Dec 2026·Techniques in Coloproctology

The first Dutch experience with a nurse-led outpatient clinic for the prevention and treatment of LARS after colorectal surgery: promising results of a standardized treatment protocol

Article

Author: van Osch, F ; Smit, C ; Konsten, J L M ; Janssen-Heijnen, M L ; van Heinsbergen, M

PURPOSE:

To report the quality of life (QoL) and functional outcomes in patients with colorectal disease after receiving treatment in a multidisciplinary, nurse-led low anterior resection syndrome (LARS) outpatient clinic post surgery.

METHODS:

A retrospective observational study was conducted that included all patients with colorectal disease referred to the LARS outpatient clinic at VieCuri Medical Centre between January 2021 and December 2024. A standardized treatment protocol was implemented, complemented by a nurse-led component that enabled early symptom detection and provided accessible, intensive patient contact and follow-up. The structured five-phase protocol ranges from preoperative counseling and conservative management to multidisciplinary care and, if necessary, invasive interventions. Bowel function and quality of life were assessed pre- and post-treatment using validated instruments, including the LARS score, Wexner score, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-C29 questionnaires.

RESULTS:

A total of 96 patients were included. Median LARS scores decreased from 38.0 to 13.0 (p < 0.001), with 76% of patients transitioning from major to no LARS. Wexner scores improved from 11.0 to 2.0 (p < 0.001), and global QoL increased from 66.7 to 83.3 (p < 0.001). Pharmacological treatment was administered to 93% of patients, most commonly psyllium and loperamide. In addition, 85% were referred to a dietitian, 50% to pelvic floor physiotherapy, and 26% to a psychologist or sexologist. Transanal irrigation was introduced in 14% of cases. Only one patient required sacral neuromodulation, and one opted for a permanent stoma. The median follow-up consisted of three in-person and three telephone consultations per patient.

CONCLUSIONS:

A multidisciplinary, nurse-led LARS clinic significantly improved bowel function and QoL in patients with colorectal cancer (CRC). These findings support the implementation of structured, individualized care pathways for LARS management.

125

News (Medical) associated with Loperamide Hydrochloride

09 Sep 2026

·www.biospace.com

U.S. FDA Grants Accelerated Approval to Bayer’s HYRNUO® (sevabertinib) as a First-Line Targeted Therapy for Patients with HER2-Mutated Non-Small Cell Lung Cancer

First-line approval of HYRNUO ® (sevabertinib) for patients with advanced HER2 -mutated non-small cell lung cancer (NSCLC) follows U.S. Food and Drug Administration (FDA) Priority Review and Breakthrough Therapy Designation Approval is based on results from the ongoing Phase I/II SOHO-01 trial evaluating the efficacy and safety of HYRNUO in patients with advanced HER2 -mutated NSCLC WHIPPANY, N.J.--(BUSINESS WIRE)--Bayer announced today that following Priority Review and Breakthrough Therapy Designation, the U.S. Food and Drug Administration (FDA) has granted accelerated approval for HYRNUO ® (sevabertinib), for the first-line treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have human epidermal growth factor receptor 2 ( HER2/ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. 1 HYRNUO is an oral, reversible, small molecule, tyrosine kinase inhibitor (TKI). The FDA approved this indication for HYRNUO under accelerated approval based on objective response rate (ORR) and duration of response (DOR) demonstrated in treatment-naïve patients (N=69, Cohort F) in the ongoing Phase I/II SOHO-01 trial (NCT05099172). 1 The trial is evaluating the efficacy and safety in patients with locally advanced or metastatic non-squamous HER2 -mutated NSCLC. 1 In this cohort, the ORR was 75% (95% CI: 64, 85; N=69) including complete responses in 6% (n=4) of patients and partial responses in 70% (n=48) of patients, with 73% of responders maintaining response for at least six months and 38% maintaining response for at least 12 months. 1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing Phase III SOHO-02 confirmatory trial (NCT06452277), which is evaluating HYRNUO versus standard of care in treatment-naïve patients with advanced HER2 -mutated NSCLC. The safety pro HYRNUO was consistent with previous findings. In the SOHO-01 study, the most common adverse reactions (>20%) in patients who received HYRNUO (N=191) were diarrhea, rash, stomatitis, paronychia, nausea and weight decreased. Please see Important Safety Information below for additional details. “The FDA’s accelerated approval of HYRNUO marks an important advance for treatment-naïve patients with HER2 -mutated NSCLC,” said SOHO-01 lead investigator, Xiuning Le, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas. “This milestone also underscores the critical importance of comprehensive molecular testing at diagnosis, including for activating HER2 mutations, to ensure patients receive the most appropriate treatment as early as possible.” “Today’s FDA approval of HYRNUO as an initial treatment option for locally advanced or metastatic non-squamous HER2 -mutated NSCLC is an important milestone for patients and a powerful validation of Bayer’s commitment to advancing precision oncology in areas with the highest unmet needs,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. “Lung cancer remains the leading cause of cancer-related deaths worldwide and for patients with HER2 -mutated NSCLC, a distinct subtype that often affects people who have never smoked, there remains a critical need for additional treatment options. 2 This approval underscores the potential of precision medicine to transform outcomes by matching the right patients to the right therapy at the right time.” “Today’s accelerated approval of HYRNUO in the first-line setting marks an important milestone for patients with HER2 -mutated locally advanced or metastatic non-squamous NSCLC,” said Nelson Ambrogio, President, Bayer U.S. Pharmaceuticals and Member of the Pharmaceuticals Leadership Team at Bayer. “We are pleased to expand access to this targeted treatment option earlier in the disease journey and continue delivering meaningful innovations to patients with difficult-to-treat cancers.” In November 2025, HYRNUO received U.S. FDA accelerated approval for patients with locally advanced or metastatic NSCLC whose tumors have HER2 TKD activating mutations, as detected by an FDA-approved test, and who received prior systemic therapy. 3 This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About HYRNUO HYRNUO is an oral, reversible, small molecule, tyrosine kinase inhibitor (TKI) that inhibits mutated human HER2 , including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with selectivity for mutated vs wild-type EGFR. HYRNUO works by blocking certain enzymes called tyrosine kinases, which are involved in the growth of cancer cells. HYRNUO is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA. About Non-Small Cell Lung Cancer (NSCLC) Lung cancer is the leading cause of cancer-related deaths worldwide. 2 NSCLC is the most common type of lung cancer, accounting for more than 85% of cases. 4 Activating HER2 mutations are found in 2% to 4% of patients with advanced NSCLC. 5 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes it difficult to treat. 6 INDICATION HYRNUO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. IMPORTANT SAFETY INFORMATION Warnings & Precautions Diarrhea HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances. In the pooled safety population, diarrhea was reported in 89% of patients who received HYRNUO including 16% Grade 3. The median time to first onset of any grade diarrhea was four days. Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 14% of patients. At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Hepatotoxicity HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests. In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 29% of patients treated with HYRNUO, including 3.1% Grade 3 and 0.3% Grade 4. Based on laboratory data, 41% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.5% Grade 3 and 0.4% Grade 4. Increased aspartate aminotransferase (AST) occurred in 44% of patients treated with HYRNUO, including 2.5% Grade 3. Increased bilirubin occurred in 15% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range: 0.2 to 24.1) months. HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.2% of patients, the dose was reduced in 4.9%, and permanently discontinued in 0.3%. Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Interstitial Lung Disease/Pneumonitis HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis. In the pooled safety population, ILD/pneumonitis occurred in four patients (1.4%) treated with HYRNUO, including 0.3% Grade 3. One patient required interruption of HYRNUO. Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis. Left Ventricular Dysfunction HYRNUO can cause severe left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has occurred with anti-HER2 therapies, including HYRNUO. Treatment with HYRNUO has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the pooled safety population, LVEF decrease occurred in one patient (0.3%) treated with HYRNUO. This Grade 3 LVEF decrease required permanent discontinuation of HYRNUO, and the event recovered. Evaluate LVEF prior to initiation of HYRNUO and monitor at regular intervals during treatment and as clinically indicated. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Ocular Toxicity HYRNUO can cause ocular toxicity. In the pooled safety population, ocular toxicity occurred in 17% of patients treated with HYRNUO, including 11% Grade 1, 4.9% Grade 2, and 0.3% Grade 3 (one case of corneal epithelial microcysts with temporary unilateral blindness). Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Pancreatic Enzyme Elevation HYRNUO can cause elevations of amylase and lipase levels. In the pooled safety population, based on laboratory data, increased amylase occurred in 39% of patients treated with HYRNUO, including 3.9% Grade 3 and 0.7% Grade 4. Increased lipase occurred in 48% of patients treated with HYRNUO, including 13% Grade 3 and 1.1% Grade 4. Four patients (1.4%) required interruption of HYRNUO due to increased lipase and three (1%) required interruption of HYRNUO due to increased amylase. One patient (0.3%) required dose reduction of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 0.7 months (range: 0.2 to 20.4 months). Monitor amylase and lipase regularly during treatment with HYRNUO. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity. Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, HYRNUO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily. Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Adverse Reactions In SOHO-01, serious adverse reactions occurred in 33% of patients who received HYRNUO. Serious adverse reactions in ≥2% of patients were diarrhea (3.7%), dyspnea (3.1%), vomiting (3.7%), pneumonia (2.6%), and pleural effusion (2.1%). A fatal adverse reaction of cerebral infarction occurred in one patient (0.5%) who received HYRNUO. The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea (90%), rash (76%), stomatitis (37%), paronychia (36%), nausea (22%) and weight decreased (22%). The most common (≥2%) Grade 3 or 4 laboratory abnormalities were lipase increased (18%), potassium decreased (18%), phosphate decreased (13%), lymphocyte count decreased (4.6%), sodium decreased (5%), amylase increased (5%), hemoglobin decreased (3.7%), ALT increased (3.2%), and increased AST (2.6%). Laboratory abnormalities in <20% of patients who received HYRNUO include bilirubin increased (19%; all were Grades 1 and 2), platelet count decreased, and neutrophil count decreased (16% each). Clinically relevant adverse reactions in <15% of patients who received HYRNUO included abdominal pain (14%), cardiac arrhythmia (10%; including arrhythmia, atrial fibrillation, atrial tachycardia, atrioventricular block complete, atrioventricular block first degree, electrocardiogram QT prolonged, sinus arrhythmia, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia, and ventricular extrasystoles), and alopecia (7%). Drug Interactions Effects of Other Drugs on HYRNUO – Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations, which may increase the risk of HYRNUO-associated adverse reactions. Monitor patients for increased HYRNUO-associated adverse reactions with moderate CYP3A inhibitors. Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dose. Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations, which may decrease the effectiveness of HYRNUO. Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers. Effects of HYRNUO on Other Drugs – Sevabertinib is a weak to moderate CYP3A inhibitor. Sevabertinib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate. Sevabertinib is a P-gp inhibitor. Sevabertinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions. Sevabertinib is an inhibitor of CYP1A1 in vitro. Sevabertinib may increase exposure of CYP1A1 substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information of CYP1A1 substrates. You are encouraged to report side effects or quality complaints of products to the FDA by visiting or calling 1-800-FDA-1088. Please see full Prescribing Information . About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. The oncology franchise at Bayer includes several marketed products across diverse indications and multiple compounds in different stages of clinical development. We have a wealth of expertise in areas including: Tumor Intrinsic Pathways, Targeted Radionuclide Therapies, and Next-Generation Immuno-Oncology. We are advancing prostate cancer treatment from early to metastatic stage, with the goal of extending survival while limiting side effects. Part of Bayer’s focus on innovative precision oncology treatments, includes an approved TRK inhibitor exclusively designed to treat tumors that have an NTRK gene fusion, the oncogenic driver of tumor growth and spread. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros. For more information, go to . © 2026 Bayer BAYER and the Bayer Cross and HYRNUO are registered trademarks of Bayer. Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References 1. HYRNUO® (sevabertinib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; September 2026. 2. World Health Organisation, Lung Cancer. Available at: 3. Bayer, U.S. FDA Approves HYRNUO® (sevabertinib) for Previously Treated Patients with HER2-Mutated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer. Available at: . 4. Emily Geraci, Lipika Chablani, Immunotherapy as a second-line or later treatment modality for advanced non-small cell lung cancer: A review of safety and efficacy, Critical Reviews in Oncology/Hematology. Available at: 5. Nützinger, J, et al. (2023). Management of HER2 alterations in non-small cell lung cancer - The past, present, and future. Lung cancer (Amsterdam, Netherlands), 186, 107385. 6. Yale Medicine Factsheet – Non-Small Cell Lung Cancer. Available at: Contacts Media Contact: Polina Miklush, Tel +1 862.431.8817 Email: polina.miklush@bayer.com

09 Sep 2026

·www.biospace.com

Sobi Receives US FDA Fast Track Designation for pacritinib in VEXAS Syndrome

WALTHAM, Mass., Sept. 09, 2026 (GLOBE NEWSWIRE) -- Sobi North America, the North American affiliate of Swedish Orphan Biovitrum AB (Sobi ® ), today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to pacritinib for the treatment of VEXAS syndrome. Pacritinib is a dual IRAK1/JAK2 inhibitor currently in Phase ll development for VEXAS syndrome. Fast Track designation is designed to facilitate the development and expedite the review of medicines to treat serious conditions that may fill an unmet medical need. “Achieving FDA’s Fast Track designation for pacritinib is an important milestone and recognizes its potential as an investigational treatment for people living with VEXAS syndrome” said Lydia Abad-Franch, MD, Head of R&D and Medical Affairs, and Chief Medical Officer at Sobi. “There is a critical need for new treatment options for people living with this debilitating condition, who often face serious complications and limited therapeutic choices. With this designation, we look forward to working even more closely with the FDA as we accelerate the clinical evaluation of pacritinib and continue to work towards approval for patients with VEXAS syndrome.” VEXAS syndrome ( V acuoles in blood-cell precursors, E 1 enzyme, X -linked, A utoinflammatory, S omatic) is a systemic disorder characterized by an overlap of hematologic and inflammatory features. VEXAS syndrome was first described in 2020. 1 It can be progressive and debilitating, with patients experiencing involvement of multiple organ systems and potentially life-threatening complications. Treatment poses a challenge as most immunomodulators fail to control the disease, resulting in a requirement for moderate to high doses of glucocorticoids. There are currently no approved treatment options for VEXAS. Since 2024, Sobi has been evaluating pacritinib in VEXAS with the PAXIS study, the first randomized trial for this condition. PAXIS ( NCT06782373 ) is a Phase II, randomized, multicenter, double-blind, placebo-controlled, dose-finding trial followed by an open-label period, designed to evaluate the efficacy and safety of pacritinib in preventing disease flares in patients with VEXAS syndrome following glucocorticoid tapering. For more information about this trial, please visit the PAXIS website and clinicaltrials.gov . 2 Topline data is expected in 2027. Contacts For details on how to contact the Sobi Investor Relations Team, please click here . For Sobi Media, click here . About Vonjo (pacritinib) VONJO (pacritinib) is a kinase inhibitor that is indicated in the US for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10 9 /L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Indication and Important Safety Information VONJO is a prescription medicine used to treat adults with certain types of myelofibrosis (MF) who have a platelet count below 50 x 10 9 /L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information VONJO can cause serious side effects, including: Bleeding. VONJO may cause severe bleeding, which can be serious and, in some cases, may lead to death. Avoid taking VONJO if you are bleeding. If you develop bleeding, stop VONJO and call your healthcare provider. Your healthcare provider will do a blood test to check your blood cell counts before you start VONJO and regularly during your treatment with VONJO. Tell your healthcare provider right away if you develop any of these symptoms: unusual bleeding, bruising, and fever. You will need to stop taking VONJO 7 days before any planned surgery or invasive procedure (such as a heart catheterization, stent placement in a coronary artery in your heart, or a procedure for varicose veins). Your healthcare provider should tell you when you can start taking VONJO again. Diarrhea. Diarrhea is common with VONJO, but can also be severe, and cause loss of too much body fluid (dehydration). Tell your healthcare provider if you have diarrhea and follow instructions for what to do to help treat diarrhea. Drink plenty of fluids to help prevent dehydration. Your healthcare provider may change your dose of VONJO if you have severe diarrhea. If you notice any change in how often you have bowel movements, if they become softer or you have diarrhea, start taking an antidiarrheal medicine (for example, loperamide) as soon as you notice changes, as directed by your healthcare provider. Worsening low platelet counts. Your healthcare provider will do blood tests to check your blood counts before you start taking VONJO and during treatment with VONJO. Changes in the electrical activity of your heart called QTc prolongation. QTc prolongation can cause irregular heartbeats that can be life-threatening. Your healthcare provider will check the electrical activity of your heart with a test called an electrocardiogram (ECG) before you start VONJO and during treatment with VONJO, as needed. If you have a history of low blood potassium, it is important that you get your blood tests done as ordered by your healthcare provider to monitor your body salts (electrolytes) in your blood. Tell your healthcare provider right away if you feel dizzy, lightheaded, or faint. Increased risk of major cardiovascular events such as heart attack, stroke, or death in people who have cardiovascular risk factors and who are current or past smokers have happened in some people taking another Janus associated kinase (JAK) inhibitor to treat rheumatoid arthritis. Get emergency help right away if you have any symptoms of a heart attack or stroke while taking VONJO, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back; severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw; pain or discomfort in your arms, back, neck, jaw, or stomach; shortness of breath with or without chest discomfort; breaking out in a cold sweat; nausea or vomiting; feeling lightheaded; weakness in one part or on one side of your body; or slurred speech. Increased risk of blood clots. Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in some people taking another JAK inhibitor and may be life-threatening. Tell your healthcare provider if you have had blood clots in the veins of your legs or lungs in the past. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with VONJO , including: swelling, pain, or tenderness in one or both legs; sudden, unexplained chest pain; or shortness of breath/difficulty breathing. Possible increased risk of new (secondary) cancers . People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers, except non-melanoma skin cancer. The risk of new cancers is further increased in people who smoke or who smoked in the past. Risk of infection. People who have certain blood cancers and take another JAK inhibitor have an increased risk of serious infections. Infections are common with VONJO, but people who take VONJO may also develop serious infections, including bacterial, mycobacterial, fungal, and viral infections. If you have a serious infection, your healthcare provider may not start you on VONJO until your infection is gone. Your healthcare provider will monitor you and treat you for any infections that you get during treatment with VONJO. Tell your healthcare provider right away if you develop any of the following symptoms of infection: chills, aches, fever, nausea, vomiting, weakness, painful skin rash, or blisters. The most common side effects of VONJO include: nausea, vomiting, low red blood cell count (anemia), and swelling of your ankles, legs, and feet. VONJO may affect fertility in males. You may have problems fathering a child. Talk to your healthcare provider if this is a concern for you. These are not all the possible side effects with VONJO. Call your doctor for medical advice about side effects. Before taking VONJO, tell your healthcare provider if you: smoke or were a smoker in the past have had previous medical conditions such as any other cancers, blood clot, heart attack, other heart problems, stroke, infection, diarrhea, commonly loose stools, nausea, vomiting, liver problems, or kidney problems have active bleeding, have had severe bleeding, or plan to have surgery. You should stop taking VONJO 7 days before any planned surgery or invasive procedures (such as a heart catheterization, stent placement in a coronary artery in your heart, or a procedure for varicose veins) are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. It is not known if VONJO will harm your unborn baby or if it passes into breast milk. You should not breastfeed during treatment and for 2 weeks after your last dose of VONJO Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking VONJO with certain other medicines may affect the amount of VONJO in your blood and may increase your risk of side effects or affect how well VONJO works. Know the medicines you take. Keep a list of the medicines you take to show your healthcare provider and pharmacist when you get a new medicine. Take VONJO exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking VONJO without first talking to your healthcare provider. If you take other kinase inhibitors, carefully follow your healthcare provider’s instructions about how to slowly decrease (taper) your dose and stop the other kinase inhibitor medicines before you begin taking VONJO. Take VONJO two times daily, with or without food, at about the same time of day. Swallow VONJO capsules whole—do not open, break, or chew capsules. If you take too much VONJO, call your healthcare provider or go to the nearest emergency room right away and take your bottle of VONJO with you. If you miss a dose, skip it, and take your next dose at your regular time—do not take 2 doses at the same time to make up for the missed dose. Your healthcare provider may change your dose or how often you take it, temporarily stop, or permanently stop treatment if you have certain side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. Please see full Prescribing Information. Sobi ® Sobi is a global biopharma company unlocking the potential of breakthrough innovations, transforming everyday life for people living with rare diseases. Sobi has approximately 2,000 employees across Europe, North America, the Middle East, Asia and Australia. In 2025, revenue amounted to SEK 28 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn . References Beck DB, Heiblig M, Savic S, et al. PAXIS: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Study (Part 1) Followed by an Open-Label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome. J Clin Med. 2026;15(4):1426. ClinicalTrials.gov. National Library of Medicine (US). Identifier NCT06782373, PAXIS: A Randomized, Double-blind, Placebo-controlled Dose-finding Phase 2 Study (Part 1) Followed by an Open-label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients With VEXAS Syndrome. Available at: .

31 Aug 2026

·www.prnewswire.com

Ziihera® (zanidatamab-hrii) plus Chemotherapy Demonstrates Statistically Significant Overall Survival Benefit Versus Trastuzumab plus Chemotherapy in First-Line HER2+ Advanced GEA

HERIZON-GEA-01 results reinforce recently FDA-approved Ziihera as the definitive HER2-targeted backbone therapy in first-line GEA Longer follow up of Ziihera plus tislelizumab and chemotherapy shows improved OS hazard ratio, further supporting this regimen as the new standard of care Data submitted for presentation in fourth quarter 2026 For U.S. media and investors only DUBLIN, Aug. 31, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced second interim top-line overall survival (OS) results from the Phase 3 HERIZON-GEA-01 trial showing that Ziihera® (zanidatamab-hrii) in combination with chemotherapy demonstrated statistically significant and clinically meaningful improvements in OS compared with trastuzumab plus chemotherapy as first-line treatment for adults with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). The Ziihera plus chemotherapy OS hazard ratio improved compared with the first interim analysis. "Advanced HER2+ GEA remains an aggressive cancer with a poor prognosis, and trastuzumab plus chemotherapy has anchored first-line treatment for years. These HERIZON-GEA-01 results show that Ziihera-based regimens extend OS, demonstrating definitive superiority of Ziihera over trastuzumab and setting a new benchmark for what a first-line HER2-targeted therapy can achieve," said Dr. Kohei Shitara, director of the Department of Gastrointestinal Oncology, and principal trial investigator at the National Cancer Center Hospital East, Kashiwa, Japan. The safety profile of Ziihera in combination with chemotherapy was generally consistent with the known safety profile of each agent and the previously reported data from HERIZON-GEA-01, with no new safety signals observed. With longer follow up, the Ziihera plus Tevimbra® (tislelizumab-jsgr) and chemotherapy OS hazard ratio improved compared with the first interim analysis. These results build on the previous positive data, published in The New England Journal of Medicine, further demonstrating statistically significant, clinically meaningful and durable OS improvement for Ziihera plus tislelizumab and chemotherapy. "These results reinforce our confidence that Ziihera is the new HER2-targeted backbone therapy in first-line HER2+ advanced GEA, replacing trastuzumab and extending survival beyond the current standard of care," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "Following the recent FDA approval, and further supported by these updated results, we are moving quickly to establish Ziihera as the HER2-targeted, first-line therapy of choice, with Ziihera plus tislelizumab and chemotherapy as the new standard of care in the United States." On August 25, 2026, the FDA approved Ziihera in combination with tislelizumab and chemotherapy, for the first-line treatment of adults with HER2+ (IHC 3+ and IHC 2+/ISH+) unresectable locally advanced or metastatic GEA, and Ziihera in combination with chemotherapy in the same setting for patients with HER2+ (IHC 3+) disease. Jazz has submitted these data for presentation at a major medical meeting in the fourth quarter 2026 and will also submit these data to global health authorities. The U.S. Prescribing Information for Ziihera contains Boxed Warnings for diarrhea and embryo-fetal toxicity. Additional Important Safety Information related to Ziihera use in GEA is provided below. Please see full Prescription, including Boxed Warnings at . About the Phase 3 HERIZON-GEA-01 Trial HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with BeOne Medicines, to evaluate and compare the efficacy and safety of zanidatamab plus chemotherapy, with and without tislelizumab, to trastuzumab plus chemotherapy as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 225 trial sites in more than 30 countries. Appropriate patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: zanidatamab in combination with chemotherapy and tislelizumab; zanidatamab in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial evaluated dual primary endpoints, PFS per blinded independent central review (BICR) and OS. About Gastroesophageal Adenocarcinoma GEA, including cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide, and approximately 20% of patients have HER2+ disease.1,2,3,4 HER2+ GEA has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 10% for patients with metastatic disease.5,6 About Ziihera ® (zanidatamab-hrii) Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces CDC, ADCC, and ADCP. These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.7 Gastroesophageal adenocarcinoma (GEA): In the United States, Ziihera is indicated for the first-line treatment of adults with HER2+ locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus, in combination with tislelizumab-jsgr and fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+ as detected by an FDA-authorized test); and in combination with fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ as detected by an FDA-authorized test). Biliary tract cancer (BTC): In the United States, Ziihera is also indicated for the treatment of adults with previously treated, unresectable or metastatic HER2+ (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.7 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).7 Ziihera is also approved in the European Union and other countries. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule.   The FDA granted three Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC; one in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab for first-line HER2+ unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal GEA; and one for the treatment of adults with previously treated, locally advanced, unresectable, or metastatic HER2+ colorectal cancer (CRC). The FDA also granted two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from the FDA for the treatment of BTC, gastric (including GEJ) cancer, and esophageal cancer, as well as Orphan Drug designations from the European Medicines Agency for the treatment of BTC, gastric/gastroesophageal junction cancer, and esophageal cancer. Jazz continues to pursue additional regulatory approvals for zanidatamab in markets worldwide. Important Safety Information for ZIIHERA Diarrhea: ZIIHERA can cause severe diarrhea. When ZIIHERA is used in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr, severe, life threatening, and fatal cases of diarrhea can occur despite loperamide prophylaxis. The risk of severe and life threatening diarrhea is higher when ZIIHERA is administered with chemotherapy and tislelizumab-jsgr, with a higher risk in patients aged ≥ 65 years compared to younger patients. Advise patients to increase oral fluids, begin antidiarrheals, and notify their healthcare provider immediately if diarrhea occurs. Administer antidiarrheal prophylaxis with loperamide in cycle 1 for all patients receiving ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr. Begin loperamide at the first loose stool when ZIIHERA is administered in combination with chemotherapy. Administer fluids, electrolytes, and additional antidiarrheal agents as necessary. Before modifying the dose of ZIIHERA, evaluate, modify or discontinue drug(s) contributing to diarrhea in accordance with their respective prescribing information. Withhold, reduce the dose, or permanently discontinue ZIIHERA based on severity. If treating patients with ZIIHERA in combination with FOLFOX, do not administer the fluorouracil bolus. ZIIHERA in combination with chemotherapy and tislelizumab-jsgr Diarrhea was reported in 85% of 330 patients in clinical studies, including Grade 4 (2.1%), Grade 3 (24%), and Grade 2 (31%) events. Fatal outcomes resulting from diarrhea occurred in 1.5% of patients. Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 3.9% of patients. In cycle 1, diarrhea at Grade 4 severity occurred in 1.5% and Grade 3 severity occurred in 15% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days. ZIIHERA in combination with chemotherapy Diarrhea was reported in 81% of 395 patients in clinical studies, including Grade 4 (1.3%), Grade 3 (20%) and Grade 2 (33%). Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 1.8% of patients. In cycle 1, diarrhea at Grade 4 severity occurred in 0.8% and Grade 3 severity occurred in 14% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days. Embryo-Fetal Toxicity: Based on the mechanism of action, ZIIHERA can cause fetal harm when administered to a pregnant woman. There are no human or animal data on the use of ZIIHERA in pregnancy. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception while receiving ZIIHERA and for 4 months following the last dose of ZIIHERA. Left Ventricular Dysfunction (LVD): ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions. The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is < 50%. ZIIHERA in combination with chemotherapy and tislelizumab-jsgr LVEF decrease (an absolute decline in LVEF of > 10%, resulting in a final value of < 50%) was observed in 9% of 330 patients in clinical studies. LVD leading to permanent discontinuation of ZIIHERA was reported in 3% of patients. Fatal outcomes due to LVD occurred in one patient (0.3%). The median time to first occurrence of LVD was 6.9 months (range: 1.2 to 29.1 months). LVD resolved in 78% of patients. ZIIHERA in combination with chemotherapy LVEF decrease was observed in 5% of 395 patients. LVD leading to permanent discontinuation of ZIIHERA was reported in 1.0% of patients. The median time to first occurrence of LVD was 6.0 months (range: 1.4 to 15.0 months). LVD dysfunction resolved in 70% of patients. Infusion-Related Reactions: ZIIHERA can cause infusion-related reactions (IRRs). Prior to each dose of ZIIHERA, administer premedication to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use. If an IRR occurs, slow or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs. ZIIHERA in combination with chemotherapy and tislelizumab-jsgr An IRR was reported in 22% of 330 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.2%), and Grade 2 (16%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.3% of patients. IRRs occurred on the first day of dosing in 17% of patients. Of all patients who experienced IRRs, 60% of reactions resolved within the first day. ZIIHERA in combination with chemotherapy An IRR was reported in 24% of 395 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.5%), and Grade 2 (18%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 1.3% of patients. IRRs occurred on the first day of dosing in 22% of patients. Of all patients who experienced IRRs, 83% of reactions resolved within the first day. Adverse Reactions ZIIHERA in combination with chemotherapy and tislelizumab-jsgr Serious adverse reactions occurred in 59% of 294 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (17%), IRR (5%), vomiting (4.8%), hypokalemia (4.4%), acute kidney injury (3.7%), pneumonia (3.7%), nausea (2.4%), decreased appetite (2.4%), and anemia (2.4%). Fatal adverse reactions occurred in 2.4% of patients and included acute kidney injury (N=2), cardiac failure, diarrhea, dehydration, hypovolemic shock and intestinal obstruction (all N=1). Permanent discontinuation of ZIIHERA occurred in 13% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included diarrhea (4.4%) and ejection fraction decreased (2.7%). The most common adverse reactions (≥ 20%) were diarrhea (83%), nausea (56%), decreased appetite (46%), vomiting (44%), hypokalemia (39%), fatigue (37%), rash (36%), peripheral neuropathy (27%), and IRR (25%). ZIIHERA in combination with chemotherapy Serious adverse reactions occurred in 49% of 305 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (11%), vomiting (3.3%), decreased appetite (2.6%), pneumonia (2.6%), sepsis (2.6%), hypokalemia (2.3%), and nausea (2.3%). Permanent discontinuation of ZIIHERA occurred in 10% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included ejection fraction decreased (2.0%), IRR (1.6%), and diarrhea (1.6%). The most common adverse reactions (≥ 20%) were diarrhea (79%), nausea (54%), vomiting (44%), decreased appetite (40%), fatigue (36%), hypokalemia (33%), peripheral neuropathy (32%), IRR (25%), and rash (22%). Pediatric Use: Safety and efficacy of ZIIHERA have not been established in pediatric patients. Geriatric Use ZIIHERA in combination with chemotherapy and tislelizumab-jsgr Of 302 patients randomized to ZIIHERA in combination with chemotherapy and tislelizumab-jsgr in HERIZON-GEA-01, there were 139 (46%) patients aged ≥ 65 years. One hundred and six (35%) were aged 65-74 years and 33 (11%) were aged ≥ 75 years. There was a higher incidence of Grade ≥ 3 adverse reactions observed in patients aged ≥ 65 years (87%) as compared to younger patients (80%). The incidence of Grade 3 or 4 diarrhea was higher in patients aged ≥ 65 years (32%) compared to younger patients (20%). There was an increased incidence of fatal adverse reactions in patients aged ≥ 65 years (4.4%); including acute kidney injury (N=2), cardiac failure, dehydration, hypovolemic shock and intestinal obstruction (all N=1), compared to younger patients (0.6%), including diarrhea (N=1). ZIIHERA in combination with chemotherapy Of 304 patients randomized to ZIIHERA in combination with chemotherapy in HERIZON-GEA-01, there were 130 (43%) patients aged ≥ 65 years. One hundred (33%) were aged 65-74 years and 30 (10%) were aged ≥ 75 years. No overall differences in safety were observed between patients aged ≥ 65 years and younger adult patients. ® TEVIMBRA (tislelizumab) is a registered trademark of BeOne Medicines. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with rare disease — often with limited or no therapeutic options. We have a diverse portfolio of medicines, including leading therapies addressing epilepsies, cancers and sleep disorders. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit for more information. Cautionary Note concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to Ziihera's potential to extend survival, Ziihera's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the successful completion of regulatory activities and uncertain regulatory approval, risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports, including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2025, and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Contacts: Media: [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Investors: [email protected] Ireland +353 1 634 7800 U.S. +1 650 496 2717 SOURCE Jazz Pharmaceuticals plc 21% more press release views with Request a Demo

Clinical ResultPhase 3Orphan DrugFast TrackBreakthrough Therapy

100 Deals associated with Loperamide Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D00729	Loperamide Hydrochloride	A07DA53 A07DA03	DB00836

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Approved

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Indication	Country/Location	Organization	Date
Acute diarrhea	Japan	Janssen Pharmaceutical KK	04 Jun 1981
Diarrhea	South Korea	Youngil Pharm	14 Apr 1976

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 3	United States	Boehringer Ingelheim GmbH	01 Apr 2013
Fallopian Tube Carcinoma	Phase 2	United States	Novartis Pharma AG	01 Sep 2001
Fallopian Tube Carcinoma	Phase 2	Canada	Novartis Pharma AG	01 Sep 2001
Fallopian Tube Carcinoma	Phase 2	Netherlands	Novartis Pharma AG	01 Sep 2001
Fallopian Tube Carcinoma	Phase 2	Slovakia	Novartis Pharma AG	01 Sep 2001
Fallopian Tube Carcinoma	Phase 2	United Kingdom	Novartis Pharma AG	01 Sep 2001
Ovarian Cancer	Phase 2	United States	Novartis Pharma AG	01 Sep 2001
Ovarian Cancer	Phase 2	Canada	Novartis Pharma AG	01 Sep 2001
Ovarian Cancer	Phase 2	Netherlands	Novartis Pharma AG	01 Sep 2001
Ovarian Cancer	Phase 2	Slovakia	Novartis Pharma AG	01 Sep 2001

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06865677 (CTgov)	Phase 2	Recurrent Cervical Cancer \| Recurrent Endometrial Cancer \| Platinum-Resistant Epithelial Ovarian Carcinoma	2	Sacituzumab Govitecan (SG) (Arm 1/Cohort 3 -Treatment With Sacituzumab Govitecan (SG))	imkljhkmol = dhsvatoidy ubvexzwspl (iithtamvpn, nojqddeucn - xlewnrccbe) View more	-	21 Jan 2026
				Sacituzumab (Participants Not Assigned to an Arm/Cohort - Treatment With Sacituzumab Govitecan (SG))	imkljhkmol = xbhkjpqhik ubvexzwspl (iithtamvpn, mmiehtoeag - zcrtwvxrqe) View more
NCT02711891 (Loperamide, CTgov)	Early Phase 1	Pain	34	Loperamide (5% Loperamide Gel)	cnkwpquwke = bkwvwcaeko ypikftrxul (tbgqhqqrrp, rvvlcjghfj - oucbhjnsjf) View more	-	19 Sep 2024
				Drug, placebo gel (Placebo Gel)	cnkwpquwke = efgceprirn ypikftrxul (tbgqhqqrrp, ljzajtjros - tzuwbsshxs) View more
NCT05520723 (PRIMED, ASCO2024) Manual	Phase 2	Advanced Triple-Negative Breast Carcinoma \| Hormone receptor positive HER2 negative breast cancer Second line \| Third line	50	Sacituzumab govitecan (SG)loperamidetecan (SG)	dflwzwcdsj(iqxfkffrio) = mzscnueiue ryhvnmqmlo (gyjciuaxtf ) View more	Positive	24 May 2024
NCT02008565 (CAPABLe, CTgov)	Phase 3	Fecal Incontinence	300	Anal exercises with biofeedback+Loperamide (Loperamide - Exercise Plus Biofeedback)	uyrytxbvhu(iiykkndhmy) = ewgkkiapeb ddjtezsagu (ldkbxfgrvk, qomzvldzfw - synspjebex) View more	-	20 Nov 2018
				Placebo (Placebo - Exercise Plus Biofeedback)	uyrytxbvhu(iiykkndhmy) = vntoelhgpa ddjtezsagu (ldkbxfgrvk, dkedlwmlpf - wduqwmpevh) View more
NCT02400476 (CONTROL, AACR 12018 \| AACR 22018) Manual	Phase 2	HER2 Positive Breast Cancer HER2 Positive	186	loperamide	msxapagoxv(zkwxjgtbuy) = wemxmhmeag sryrhusgry (nnhkyeotow )	Positive	15 Feb 2018
				loperamide+budesonide	msxapagoxv(zkwxjgtbuy) = lxcxhybvrt sryrhusgry (nnhkyeotow )
NCT02266849 (Pubmed \| Basic Clin Pharmacol Toxicol)	Phase 3	-	12	Loperamide 12 mg/day	egcqjoooby(hzemlxykep) = yfyrhwxxnf tzbuhenrco (stcszxlsqk )	-	01 Dec 2017
NCT01618591 (Pubmed \| Clin Infect Dis)	Not Applicable	Turista	384	Azithromycin	crrsukmfdu(tunhmitjei) = kgobskshuy bxebpzqfzo (koesbxhmhg ) View more	-	29 Nov 2017
				Levofloxacin	crrsukmfdu(tunhmitjei) = sogbeeuack bxebpzqfzo (koesbxhmhg ) View more
NCT02400476 (CONTROL, SABCS2017)	Phase 2	HER2 Positive Breast Cancer HER2+	133	Neratinib + Loperamide prophylaxis	bohjpqmkut(heblpvcjuq) = bfkezuurxr wucmdzhgps (zrbgitcwjr ) View more	Positive	15 Feb 2017
				Neratinib + Loperamide + Budesonide prophylaxis	bohjpqmkut(heblpvcjuq) = igzhkyuznk wucmdzhgps (zrbgitcwjr ) View more
NCT02217982 (IIT9, CTgov)	Phase 4	Multiple Sclerosis, Relapsing-Remitting	5	DMF (Control Group)	zdzhfuatnw(bmmeplthus) = gtfpdaygbi hosrstoijr (bxwpvipaod, cfqtheplpz - oqxikmcebq) View more	-	06 Jan 2017
				Peanut Butter+Simethicone+Loperamide (Treatment Arm)	zdzhfuatnw(bmmeplthus) = iexcypjbjw hosrstoijr (bxwpvipaod, jlbzjnbacr - ozfcqplqbk) View more
NCT02099006 (Topicals, CTgov)	Phase 2/3	Vulvodynia \| Genital Diseases, Female \| Reproductive tract disorder	9	Baclofen+Amitriptyline+ketoprofen+Loperamide+Ketamine+Gabapentin (Medications)	jwrclufuyd(mnpuachaaq) = akdprwahcx frvjhzaxay (seeuerzvex, 1.94) View more	-	15 Jul 2016
				placebo (Placebo)	jwrclufuyd(mnpuachaaq) = qbpnvjitsl frvjhzaxay (seeuerzvex, 2.3) View more

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Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis