[Translation] A randomized, open-label, single-dose, two-formulation, two-sequence, two-period, crossover, fed-state bioequivalence study of clarithromycin extended-release tablets in healthy volunteers

主要目的：在中国健康受试者中评价餐后条件下浙江普利药业有限公司生产的克拉霉素缓释片（受试制剂，500mg）与欧盟上市克拉霉素缓释片（参比制剂，Klacid®SR，持证商：MylanHealthcareB.V.，500mg）的人体生物等效性。次要目的：观察餐后条件下克拉霉素缓释片受试制剂和参比制剂在中国健康受试者中的安全性。

[Translation]

Primary objective: To evaluate the bioequivalence of clarithromycin extended-release tablets (test preparation, 500 mg) produced by Zhejiang Puli Pharmaceutical Co., Ltd. and clarithromycin extended-release tablets (reference preparation, Klacid® SR, licensee: Mylan Healthcare B.V., 500 mg) marketed in the EU in healthy Chinese subjects under fed conditions. Secondary objective: To observe the safety of clarithromycin extended-release tablets test preparation and reference preparation in healthy Chinese subjects under fed conditions.

Start Date26 Nov 2024

Sponsor / Collaborator

Zhejiang Puli Pharmaceutical Co., Ltd.

KCT0009996

/ RecruitingPhase 4IIT

Efficacy and safety of proton pump inhibitor-based triple therapy with half dose clarithromycin for clarithromycin sensitive Helicobacter pylori eradication

Start Date24 Sep 2024

Sponsor / Collaborator

Chonnam National University Hospital

NCT06551623

/ CompletedPhase 1

A Single Center, Open Label, Phase 1 Study in Healthy Participants to Investigate the Drug-Drug Interactions Between TNP-2198 and Midazolam, Clarithromycin

This is a single center, open label, drug-drug interaction, Phase 1 study of TNP-2198 in approximately 32 healthy participants, includes 2 cohorts (16 participants per cohort): Midazolam cohort and Clarithromycin cohort. Midazolam cohort will evaluate the effect of multiple oral doses of TNP-2198 capsules on the pharmacokinetics (PK) parameters of a single oral dose of midazolam, a cytochrome P-450 (CYP) 3A sensitive substrate, in healthy participants; Clarithromycin cohort will evaluate the effect of multiple oral doses of clarithromycin tablets, a strong CYP3A and P-gp inhibitor, on the PK parameters of multiple oral doses of TNP-2198 in healthy participants.

Start Date26 Aug 2024

Sponsor / Collaborator

TenNor Therapeutics Suzhou Ltd.

100 Clinical Results associated with Clarithromycin

100 Translational Medicine associated with Clarithromycin

100 Patents (Medical) associated with Clarithromycin

20,286

Literatures (Medical) associated with Clarithromycin

01 Sep 2025·CURRENT DIABETES REVIEWS

Efficacy of Adjunctive Local Antimicrobials to Non-Surgical Periodontal Therapy in Pocket Reduction and Glycemic Control of Patients with Type 2 Diabetes: A Network Meta-Analysis

Article

Author: da Rocha Nogueira Filho, Getulio ; Martins-Pfeifer, Carolina Castro ; Stefani, Cristine Miron ; de Souza, Ana Luiza Magalhães ; de Oliveira, Domitilla Marchiori Sant’Anna Leal

Objective::

This network meta-analysis [NMA] investigated the efficacy of adjunctive use of subgingivally delivered antimicrobials to non-surgical periodontal therapy [NSPT] in the glycemic control and periodontal pocket depth (PPD) reduction in patients with type 2 diabetes (T2D).

Methods::

Seven databases, grey literature, and registry platforms were searched up to February 2024 to identify randomized clinical trials (RCT) fulfilling the eligibility criteria. The risk of bias was assessed through Cochrane’s tool (RoB 2). Two frequentist NMA were performed using a random-effects model to calculate mean differences (MD) as an effect measure and to quantitatively evaluate the glycated hemoglobin (HbA1c) and PPD. The certainty of evidence was assessed through the GRADE approach in a partially contextualized framework for interpreting results. Ten RCTs were included.

Results::

In total, 261 patients were treated with eight different local antimicrobials adjuvants to NSPT (azithromycin gel, clarithromycin gel, tetracycline fiber or ointment, chlorhexidine gel, doxycycline nanospheres, minocycline gel, and satranidazole gel), while 249 patients received NSPT alone or associated to placebo. Considering PPD reduction (8 included studies), the best results were found after six months for satranidazole gel (MD -2.64mm; 95%CI -3.56, -1.72; moderate evidence certainty). For HbA1c control (7 included studies), doxycycline gel (MD - 0.80%; 95%CI -1.70, 0.10), chlorhexidine gel (MD -0.68%; 95%CI -1.34, -0.02), and tetracycline fiber (MD -0.62%; 95%CI -0.85, -0.39) showed promising results after three months (low evidence certainty).

Conclusion::

The adjunctive use of satranidazole gel probably reduces PPD after a 6-month follow-up, while doxycycline gel, chlorhexidine gel, and tetracycline fiber may decrease HbA1c values in patients with T2D and periodontitis treated with NSPT after a 3-month follow up.

01 Apr 2025·JOURNAL OF COLLOID AND INTERFACE SCIENCE

Oral glucose-responsive nanoparticles loaded with artemisinin induce pancreatic β-cell regeneration for the treatment of type 2 diabetes

Article

Author: Chen, Jiapeng ; Pan, Shengjun ; Chen, Zhendong ; Zhai, Limin ; Guo, Yiyan ; Zheng, Yuxin ; Guan, Yan-Qing ; Xu, Haoming ; Liang, Xuanxi

Type 2 diabetes (T2D) is a chronic disease characterized by long-term insulin resistance (IR) and pancreatic β-cell dysfunction. Conventional T2D medication ignores pancreatic β-cell damage. In this study, we designed an oral glucose-responsive nanoparticle for pancreatic β-cell regeneration and treatment of T2D. It was formed by carboxymethyl chitosan (CMC) grafted with 3-aminophenylboronic acid (APBA) as the shell and small-molecule citrus pectin (MCP) spheres encapsulating artemisinin (Art) connected by borate ester bonds. The prepared CMC-APBA wrapped Art-loaded MCP nanoparticles (CAM@Art) had therapeutic effects for the treatment of IR, antioxidant and promotion of pancreatic α-cell differentiation in vitro experiments. In addition, in vivo experiments showed that CAM@Art could reduce blood glucose, oxidative stress and inflammation levels and reverse IR in diabetic rats. Importantly, pancreatic β-cell regeneration was found in islets in vivo. Mechanistically, CAM@Art promotes pancreatic α-cell differentiation by promoting overexpression of the transcription factor Pax4 and ectopic expression of Arx. The results suggest that the present study provides a promising therapeutic strategy for the treatment of diabetic pancreatic β-cell dysfunction.

01 Apr 2025·ENVIRONMENTAL RESEARCH

Temporal dynamics of the soil resistome and microbiome irrigated with treated wastewater containing clarithromycin

Article

Author: Bastos, Marilia Camotti ; Chiron, Serge ; Ait-Mouheb, Nassim ; Della-Negra, Oriane ; Patureau, Dominique ; Bru-Adan, Valérie ; Santa-Catalina, Gaëlle

Clarithromycin, a common antibiotic found in domestic wastewater, persists even after treatment and can transfer to soils when treated wastewater (TWW) is used for irrigation. This residual antibiotic may exert selection pressure, promoting the spread of antibiotic resistance. While Predicted No Effect Concentrations (PNECs) are used in liquid media to predict resistance risks, PNEC values for soils, especially for clarithromycin, are lacking. Thus, this study aimed to assess clarithromycin's fate and its concentration threshold affecting soil microbial communities and macrolide resistance genes. The study used a soil microcosm approach with TWW containing clarithromycin at concentrations of 0, 0.01, 0.1, 0.5, and 1 mg/kg_{dry soil} over a three-month period. Results showed clarithromycin persisted with limited degradation, likely due to strong adsorption to soil particles. Two transformation products were identified: decladinose-CLA (abiotic degradation) and phosphate-CLA (bacterial phosphotransferase activity). Soil bacterial communities were more influenced by TWW than by clarithromycin itself, as its antimicrobial effect was reduced due to adsorption. While clarithromycin did not significantly affect the abundance of resistance genes like intl1, mphA, and ereA, concentrations above 0.01 mg/kg increased the ermB gene abundance during the first week. The mefA gene (macrolide efflux pump) showed a hormetic effect: low doses (<0.1 mg/kg) increased gene abundance, while higher doses (>0.5 mg/kg) inhibited gene transfer or the bacteria carrying it. This study performed under controlled conditions provided insights into antibiotic resistance dynamics in soils exposed to clarithromycin, highlighting key concentration thresholds influencing resistance spread in soils.

150

News (Medical) associated with Clarithromycin

21 Jan 2025

·www.prnewswire.com

RedHill's Talicia® Adds 8 Million Lives With Coverage by Humana®'s Part D Plan. Also, New Data Supporting Simplified Three-Times Daily Talicia Dosing Published

Talicia is now covered by Humana's Part D Plan, providing access to Talicia for H. pylori therapy to more than eight million additional Medicare lives, without requiring prior therapeutic steps or authorization The recently updated American College of Gastroenterology (ACG) Clinical Guideline lists Talicia as a first-line option for treatment of H. pylori infection. Talicia continues to be the most prescribed branded H. pylori therapy by U.S. gastroenterologists Additionally, new data describing the foundations for Talicia's recent FDA-approved label change to a more convenient three-times daily (TID) "breakfast, lunch, and dinner" dosing routine, supporting patient adherence, has been published in the Journal of Clinical Pharmacology The published data describe the use of physiologically-based pharmacokinetic (PBPK) modeling and simulation to demonstrate pharmacokinetic equivalence of the TID regimen to the previous every 8-hour (Q8H) dosing regimen H. pylori infection affects approximately 35% of the U.S. adult population and is classified by the World Health Organization (WHO) as a Group 1 carcinogen, being the strongest known risk factor for gastric cancer and a major risk factor for peptic ulcer disease RALEIGH, N.C. and TEL-AVIV, Israel, Jan. 21, 2025 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced the coverage of Talicia by Humana's Part D Plan, providing access to Talicia for H. pylori therapy to more than eight million additional Medicare lives, without the requirement for prior therapeutic steps or authorizations, for both treatment-naïve and treatment-experienced patients, effective as of January 1, 2025. "There is broad recognition of the clinical efficacy of Talicia and the recently updated American College of Gastroenterology (ACG) Clinical Guideline, listing Talicia as a first-line treatment option. Talicia is the only FDA-approved low-dose rifabutin-based therapy for the eradication of H. pylori, and continues to be the most prescribed branded H. pylori therapy by U.S. gastroenterologists1," said Rick D. Scruggs, President and Chief Commercial Officer of RedHill Biopharma, Inc. "We are pleased that coverage in the Medicare arena is growing as the Part D payers recognize the importance of treating H. pylori with the right therapy the first time and look forward to expanding coverage in Medicare." The Company also announced the publication of new data in The Journal of Clinical Pharmacology2. The published data describe the foundations for Talicia's recently FDA-approved label change to a more convenient three-times daily (TID) with food (at least 4 hours apart, e.g., breakfast, lunch, and dinner) dosing routine, further simplifying the patient experience and supporting increased patient adherence. The result of a successful collaboration with Certara, the published study utilized Certara's Simcyp™ Simulator for physiologically-based pharmacokinetic (PBPK) modeling and simulation to demonstrate pharmacokinetic equivalence in plasma and within the stomach for all three of Talicia's components, regardless of dosing TID or Q8H. These data support the provision of a more patient-friendly Talicia regimen and further demonstrate RedHill's ongoing commitment to enhanced patient experience and outcomes. "Treating H. pylori infection is challenging and often requires patients to take multiple different pills multiple times a day. Simplified dosing regimens improve patient adherence. In the treatment of H. pylori infection, adherence to dosing is critical for optimizing patient outcomes, while also mitigating against the development of bacterial resistance. Therefore, it is important to use an effective therapy that is most likely to eradicate H. pylori infection at the first attempt," said Colin W. Howden, MD, Professor Emeritus, University of Tennessee College of Medicine, and co-author of the paper. "These important data, and the retention of Talicia's pharmacokinetic profile across dosing regimens, support the change to a more simplified TID dosing schedule. Talicia's efficacy, tolerability, and resistance profile, along with its convenient all-in-one formulation and TID dosing, further support its inclusion as an empirically prescribed first-line option in the 2024 ACG Clinical Guideline on the treatment of H. pylori infection3." About H. pylori H. pylori is a bacterial infection that affects approximately 35%4 of the U.S. population, with an estimated two million patients treated annually3. Worldwide, around 66% of the population has H. pylori infection5, which is classified by the World Health Organization (WHO) as a Group 1 carcinogen. It remains the strongest known risk factor for gastric cancer6 and a major risk factor for peptic ulcer disease7 and gastric mucosa-associated lymphoid tissue (MALT) lymphoma8. More than 27,000 Americans are diagnosed with gastric cancer annually9. Eradication of H. pylori is becoming increasingly difficult, with current therapies failing in approximately 25-40% of patients who remain H. pylori-positive due to high resistance of H. pylori to antibiotics – especially clarithromycin – which is still commonly used in standard combination therapies10. About Talicia® Talicia is the only low-dose rifabutin-based therapy approved for the treatment of H. pylori infection and is designed to address the high resistance of H. pylori bacteria seen with other antibiotics. More specifically, the high rates of H. pylori resistance to clarithromycin have led to significant increases in treatment failures with clarithromycin-based therapies and are a strong public health concern, as highlighted by the ACG, FDA and the WHO in recent years. Talicia is a novel, fixed-dose, all-in-one oral capsule combination of two antibiotics (amoxicillin and rifabutin) and a proton pump inhibitor (PPI) (omeprazole). In November 2019, Talicia was approved by the U.S. FDA for the treatment of H. pylori infection in adults. In the pivotal Phase 3 study, Talicia demonstrated 84% eradication of H. pylori infection in the intent-to-treat (ITT) group vs. 58% in the active comparator arm (p<0.0001). Minimal to zero resistance to rifabutin, a key component of Talicia, was detected in RedHill's pivotal Phase 3 study. Further, in an analysis of data from this study, it was observed that subjects who were confirmed adherent11 to their therapy had response rates of 90.3% in the Talicia arm vs. 64.7% in the active comparator arm12. Talicia is eligible for a total of eight years of U.S. market exclusivity under its Qualified Infectious Disease Product (QIDP) designation and is also covered by U.S. patents which extend patent protection until 2034 with additional patents and applications pending and granted in various territories worldwide. Patients should check coverage details with their health plan. TALICIA: INDICATION AND IMPORTANT SAFETY INFORMATION Talicia is a three-drug combination of omeprazole, a proton pump inhibitor, amoxicillin, a penicillin-class antibacterial, and rifabutin, a rifamycin antibacterial, indicated for the treatment of Helicobacter pylori infection in adults. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Talicia and other antibacterial drugs, Talicia should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. IMPORTANT SAFETY INFORMATION Talicia contains omeprazole, a proton pump inhibitor (PPI), amoxicillin, a penicillin-class antibacterial and rifabutin, a rifamycin antibacterial. It is contraindicated in patients with known hypersensitivity to any of these medications, any other components of the formulation, any other beta-lactams or any other rifamycin. Talicia is contraindicated in patients receiving rilpivirine-containing products. Talicia is contraindicated in patients receiving delavirdine or voriconazole. Serious and occasionally fatal hypersensitivity reactions have been reported with omeprazole, amoxicillin and rifabutin. Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of Talicia. Severe cutaneous adverse reactions (SCAR) (e.g., Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN)) have been reported with rifabutin, amoxicillin, and omeprazole. Additionally, drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported with rifabutin. Acute Tubulointerstitial Nephritis has been observed in patients taking PPIs and penicillins. Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range from mild diarrhea to fatal colitis. Talicia may cause fetal harm. Talicia is not recommended for use in pregnancy. Talicia may reduce the efficacy of hormonal contraceptives. An additional non-hormonal method of contraception is recommended when taking Talicia. Talicia should not be used in patients with hepatic impairment or severe renal impairment. Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs. These events have occurred as both new onset and exacerbation of existing autoimmune disease. The most common adverse reactions (≥1%) were diarrhea, headache, nausea, abdominal pain, chromaturia, rash, dyspepsia, oropharyngeal pain, vomiting, and vulvovaginal candidiasis. To report SUSPECTED ADVERSE REACTIONS, contact RedHill Biopharma INC. at 1-833-ADRHILL (1-833-237-4455) or FDA at 1-800-FDA-1088 or . Full prescribing information for Talicia is available at . About RedHill Biopharma RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on U.S commercialization and development of drugs for gastrointestinal diseases, infectious diseases and oncology. RedHill promotes the gastrointestinal drug Talicia®, for the treatment of Helicobacter pylori (H. pylori) infection in adults13. RedHill's key clinical late-stage development programs include: (i) opaganib (ABC294640), a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple indications with U.S. government and academic collaborations for development for radiation and chemical exposure indications such as Acute Radiation Syndrome (ARS), a Phase 2/3 program for hospitalized COVID-19, and a Phase 2 program in oncology; (ii) RHB-107 ( upamostat), an oral broad-acting, host-directed, serine protease inhibitor with potential for pandemic preparedness is in late-stage development as a treatment for non-hospitalized symptomatic COVID-19, with non-dilutive external funding covering the entirety of the RHB-107 arm of the 300-patient Phase 2 adaptive platform trial, and is also targeting multiple other cancer and inflammatory gastrointestinal diseases; (iii) RHB-102, with potential UK submission for chemotherapy and radiotherapy induced nausea and vomiting, positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; and (v) RHB-204, a Phase 3-stage program for pulmonary nontuberculous mycobacteria (NTM) disease. More information about the Company is available at / X.com/RedHillBio. Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and may discuss investment opportunities, stock analysis, financial performance, investor relations, and market trends. Such statements may be preceded by the words "intends," "may," "will," "plans," "expects," "anticipates," "projects," "predicts," "estimates," "aims," "believes," "hopes," "potential" or similar words and include, among others, statements regarding the potential effects of Talicia® in the treatment of Helicobacter pylori infection. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company's control and cannot be predicted or quantified, and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation: market and other conditions; the Company's ability to maintain compliance with the Nasdaq Capital Market's listing requirements; the risk that the addition of new revenue generating products or out-licensing transactions will not occur; the risk that acceptance onto the RNCP Product Development Pipeline will not guarantee ongoing development or that any such development will not be completed or successful; the risk that the FDA does not agree with the Company's proposed development plans for opaganib for any indication; the risk that observations from preclinical studies are not indicative or predictive of results in clinical trials; the risk that the FDA pre-study requirements will not be met and/or that the Phase 3 study of RHB-107 in COVID-19 outpatients will not be approved to commence or if approved, will not be completed or, should that be the case, that we will not be successful in obtaining alternative non-dilutive development funding for RHB-107; the risk that RHB-107's late-stage development for non-hospitalized COVID-19 will not benefit from the resources redirected from the terminated RHB-204 Phase 3 study, and that the Phase 2/3 COVID-19 study for RHB-107 may not be successful and, even if successful, such studies and results may not be sufficient for regulatory applications, including emergency use or marketing applications, and that additional COVID-19 studies for opaganib and RHB-107 are likely to be required; the risk that the Company will not successfully commercialize its products; as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company's research, manufacturing, pre-clinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its commercial products and ones it may acquire or develop in the future; (ii) the Company's ability to advance its therapeutic candidates into clinical trials or to successfully complete its pre-clinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number and type of additional studies that the Company may be required to conduct and the Company's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company's therapeutic candidates and Talicia®; (v) the Company's ability to successfully commercialize and promote Talicia®; (vi) the Company's ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company's therapeutic candidates and the results obtained with its therapeutic candidates in research, pre-clinical studies or clinical trials; (ix) the implementation of the Company's business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company's expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company's industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on April 8, 2024. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise unless required by law. All information contained herein is the sole responsibility of RedHill Biopharma Ltd. Company contact: Adi Frish Chief Corporate & Business Development Officer RedHill Biopharma +972-54-6543-112 [email protected] Category: Commercial 1 IQVIA XPO Data on file 2 Vakil N, Howden CW, Shah SC, Chen KF, Offman E, Almenoff JS, Sheldon KL. Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication. J Clin Pharmacol. 2025 Jan 2. doi: 10.1002/jcph.6178. Epub ahead of print. PMID: 39745109. 3 Chey, William D. MD, FACG1; Howden, Colin W. MD, FACG2; Moss, Steven F. MD, FACG3; Morgan, Douglas R. MD, MPH, FACG4; Greer, Katarina B. MD, MSEpi5; Grover, Shilpa MD, MPH6; Shah, Shailja C. MD, MPH7. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. The American Journal of Gastroenterology 119(9):p 1730-1753, September 2024. | DOI: 10.14309/ajg.0000000000002968 4 Hooi JKY et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology 2017; 153:420-429. 5 6 Lamb A et al. Role of the Helicobacter pylori–Induced inflammatory response in the development of gastric cancer. J Cell Biochem 2013;114.3:491-497. 7 NIH – Helicobacter pylori and Cancer, September 2013. 8 Hu Q et al. Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori infection: a review of current diagnosis and management. Biomarker research 2016;4.1:15. 9 National Cancer Institute, Surveillance, Epidemiology, and End Results Program (SEER). 10 Malfertheiner P. et al. Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report, Gut 2012;61:646-664; O'Connor A. et al. Treatment of Helicobacter pylori Infection 2015, Helicobacter 20 (S1) 54-61; Venerito M. et al. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion 2013;88(1):33-45. 11 Defined as the PK population which included those subjects in the ITT population who had demonstrated presence of any component of investigational drug at visit 3 (approx. day 13) or had undetected levels drawn >250 hours after the last dose. 12 The pivotal Phase 3 study with Talicia® demonstrated 84% eradication of H. pylori infection with Talicia® vs. 58% in the active comparator arm (ITT analysis, p<0.0001). 13 Talicia® (omeprazole magnesium, amoxicillin and rifabutin) is indicated for the treatment of H. pylori infection in adults. For full prescribing information see: . Logo - SOURCE RedHill Biopharma Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 3Clinical ResultDrug Approval

11 Dec 2024

·www.globenewswire.com

Phathom Pharmaceuticals Submits Citizen Petition to FDA Seeking Correction of Orange Book Listings for VOQUEZNA® (vonoprazan) Tablets

Citizen Petition seeks correction of expiration date for New Chemical Entity (NCE) exclusivity on VOQUEZNA (vonoprazan) tablets Orange Book listingsPhathom believes applicable law mandates a 10-year NCE exclusivity period (from date of first approval of drug containing vonoprazan) benefitting all vonoprazan-based products, with exclusivity until May 3, 2032 FLORHAM PARK, N.J., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal (GI) diseases, announced today it has submitted a Citizen Petition (CP) with the U.S. Food and Drug Administration (FDA). The petition formally requests correction of the Orange Book listings for VOQUEZNA (vonoprazan) 10 mg and 20 mg tablets to accurately reflect the full 10-year NCE exclusivity period until May 3, 2032. The update would align the VOQUEZNA tablets Orange Book listings to reflect the same period of NCE exclusivity that was granted upon approval of vonoprazan-based VOQUEZNA TRIPLE PAK® and VOQUEZNA DUAL PAK® in May 2022. The statutory 10-year exclusivity period encompasses the five-year standard exclusivity period for NCEs as extended by the additional five years by operation of the Generating Antibiotic Incentives Now (GAIN) Act. As VOQUEZNA tablet products contain the same drug substance with the active moiety, vonoprazan, they should be entitled to the same protection. The main points addressed in Phathom’s Citizen Petition include: New Chemical Entity Exclusivity Provisions: The approval of VOQUEZNA TRIPLE PAK and VOQUEZNA DUAL PAK in May 2022 triggered a 10-year NCE exclusivity period by operation of the GAIN Act, tied to the drug substance containing vonoprazan, which had never previously been approved. This exclusivity period expires in May 2032. Under the law and FDA’s longstanding interpretations of it, NCE exclusivity precludes the submission of any Abbreviated New Drug Application (ANDA) or 505(b)(2) New Drug Application (NDA) referencing any drug containing vonoprazan for the NCE exclusivity period, including VOQUEZNA tablets.The GAIN Act: The NCE exclusivity period awarded upon approval of VOQUEZNA DUAL PAK and VOQUEZNA TRIPLE PAK is 10 years. This is because the GAIN Act’s application to the approval of VOQUEZNA DUAL PAK and VOQUEZNA TRIPLE PAK was to extend, by five years, the underlying NCE exclusivity tied to the drug substance containing vonoprazan. While the GAIN Act includes certain limitations on the application of the extension, none of these exceptions have any effect on the 10-year NCE exclusivity period already awarded and honored by the FDA, and such 10-year NCE exclusivity period equally benefits any vonoprazan-containing products, including VOQUEZNA tablets.Established and Sound Public Policy: As mandated by the plain language of the applicable statutes and the FDA’s longstanding interpretations, Phathom requests that the FDA promptly correct the Orange Book to accurately reflect the statutorily-required 10-year period of NCE exclusivity for vonoprazan in the Orange Book listings for the VOQUEZNA tablet products, identifying the correct expiry date of May 3, 2032. “We are committed to ensuring VOQUEZNA tablets receive the full exclusivity protections in accordance with the FDA's longstanding policies and the clear language of the law,” said Terrie Curran, President and Chief Executive Officer of Phathom Pharmaceuticals. “We remain confident in our position that VOQUEZNA tablets are entitled to the full ten-years of NCE exclusivity on the basis of the approval of vonoprazan in VOQUEZNA TRIPLE PAK and DUAL PAK. If corrected, we expect NCE exclusivity for VOQUEZNA tablets until May 3, 2032, which is an enhancement to our patent term exclusivity that is expected to be extended into 2030.” Phathom expects the CP and related docket information to be made available on the www.regulations.gov website in the coming days. The FDA must provide a response to the petition within 180 days from the date of submission. The response will either approve the petition, deny or dismiss the petition, or provide a tentative response indicating why the agency hasn’t been able to reach a decision. The Company believes that a CP affords the FDA the ability to analyze the request under an established framework, and ultimately formalize its decision in accordance with its procedural regulations. About VOQUEZNA®VOQUEZNA® (vonoprazan) tablets contain vonoprazan, an oral small molecule potassium-competitive acid blocker (PCAB). PCABs are a novel class of medicines that block acid secretion in the stomach. VOQUEZNA is approved in the U.S. for the treatment of adults with Erosive Esophagitis, also known as Erosive GERD, the relief of heartburn associated with Erosive GERD, the relief of heartburn associated with Non-Erosive GERD, and for the treatment of H. pylori infection in combination with either amoxicillin or amoxicillin and clarithromycin. Phathom in-licensed the U.S. rights to vonoprazan from Takeda, which markets the product in Japan and numerous other countries in Asia and Latin America. About Phathom Pharmaceuticals, Inc.Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases. Phathom has in-licensed the exclusive rights to vonoprazan, a first-in-class potassium-competitive acid blocker (PCAB) that is currently marketed in the United States as VOQUEZNA® (vonoprazan) tablets for the treatment of heartburn associated with Non-Erosive GERD in adults, the healing and maintenance of healing of Erosive GERD in adults and relief of associated heartburn, in addition to VOQUEZNA® TRIPLE PAK® (vonoprazan tablets, amoxicillin capsules, clarithromycin tablets) and VOQUEZNA® DUAL PAK® (vonoprazan tablets, amoxicillin capsules) for the treatment of H. pylori infection in adults. For more information about Phathom, visit the company’s website at www.phathompharma.com and follow on LinkedIn and X. Forward-Looking StatementsThis press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about: the ultimate decision by the FDA on the action requested in the CP and the timing any FDA action regarding the CP; the possible extension of NCE exclusivity to VOQUEZNA tablets; and the expected duration of patent term extension for VOQUEZNA. The inclusion of forward-looking statements should not be regarded as a representation by Phathom that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Phathom’s business, including, without limitation: the FDA may reject our request to correct the Orange Book listings identifying the expiration date for the NCE exclusivity period on the VOQUEZNA tablets Orange Book listings; the FDA may take longer that we expect to act on our CP, if at all; members of the public may comment on our CP which may influence the FDA’s decision; our ability to obtain and maintain intellectual property protection, including patent term extensions, and non-patent regulatory exclusivity for vonoprazan; we may face competition earlier than expected if we lose or fail to obtain any of our patent protection or non-patent regulatory exclusivity for VOQUEZNA tablets; and other risks described in the Company’s prior press releases and the Company’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Phathom undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. MEDIA CONTACTNick Benedetto1-877-742-8466media@phathompharma.com INVESTOR CONTACTEric Sciorilli1-877-742-8466ir@phathompharma.com © 2024 Phathom Pharmaceuticals. All rights reserved.VOQUEZNA, VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, Phathom Pharmaceuticals, and their respective logos are registered trademarks of Phathom Pharmaceuticals, Inc.

Drug ApprovalLicense out/inNDA

18 Nov 2024

·www.prnewswire.com

TenNor Announces Positive Topline Results from Rifasutenizol Phase III Trial for H. pylori Infection

SUZHOU, China, Nov 18, 2024 /PRNewswire/ -- TenNor Therapeutics, a clinical-stage company dedicated to developing novel therapies to address unmet needs in infectious diseases, announced today the successful completion of a phase III clinical trial of rifasutenizol (TNP-2198) for the treatment of Helicobacter pylori (H. pylori) infection. The study met its primary endpoints, showing multiple advantages of rifasutenizol regimen compared with bismuth-containing quadruple therapy (BQT), the current standard of care. The completed study is a multicenter, randomized, double-blind, controlled phase III clinical trial to evaluate the efficacy and safety of TNP-2198 in combination with amoxicillin and rabeprazole for the treatment of H. pylori infection in treatment-naive patients. The study was conducted in 40 hospitals in China. A total of 700 treatment-naive patients with H. pylori infection confirmed by a positive carbon-13 urea breath test (C-13 UBT) and histological examination were randomly assigned in a 1:1 ratio to receive rifasutenizol triple therapy (rifasutenizol 400 mg, amoxicillin 1 g and rabeprazole 20 mg) or BQT (bismuth potassium citrate 240 mg, clarithromycin 500 mg, amoxicillin 1 g and rabeprazole 20 mg) treatment, twice a day for 14 days. The efficacy endpoint was the C-13 UBT test result 4 to 6 weeks after the end of treatment. Patient compliance was high in the study with a low dropout rate of 3%. H. pylori was successfully cultured in 87% patients. There were no significant differences in demographics or baseline antibiotic resistance characteristics between the two treatment groups that could affect the study outcomes. Resistance rates to clarithromycin, metronidazole, levofloxacin and amoxicillin among H. pylori clinical isolates from this study were 41%, 68%, 35% and 8% respectively, which are consistent with data reported recently by other studies, indicating antibiotic resistance to H. pylori is a serious problem in China. All clinical isolates from the study were susceptible to rifasutenizol. Rifasutenizol triple therapy achieved >90% eradication rate in the modified intention-to-treat (mITT) population, higher than BQT control (92.0% vs. 87.9%, difference 4.1%, non-inferiority test p<0.0001, superiority test p= 0.0338). The rifasutenizol regimen also achieved a higher eradication rate than BQT in the per protocol (PP) population (93.7% vs. 90.3%, difference 3.4%, non-inferiority test p<0.0001, superiority test p=0.0563). In patients infected with H. pylori resistant to any of the current antibiotics, rifasutenizol triple therapy also achieved a higher eradication rate than BQT (90.9% vs. 87.2%, difference 3.7%, non-inferiority test p<0.0001), indicating rifasutenizol regimen is highly effective in patients with antibiotic-resistant H. pylori infections. Rifasutenizol regimen showed better safety and tolerability profile than BQT. The treatment-emergent adverse events (TEAEs), investigational drug related TEAEs, TEAEs with grade 3 or above are all lower in the rifasutenizol arm. Most TEAEs were Grade 1 and no investigational drug related serious adverse events (SAEs) reported. Rifasutenizol is a novel multi-targeting drug candidate with a synergistic mechanism of action against anaerobic and microaerophile bacteria. It has potential to become the first new drug developed specifically for H. pylori infection in more than 30 years. Rifasutenizol could play an important role in supporting the large-scale test-and-treatment strategy to prevent gastric cancers in populations with high gastric cancer risk, as the rifasutenizol regimen does not require drug sensitivity test and can be seamlessly integrated with the UBT testing. TenNor completed 7 phase I-III clinical trials in China and has received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the U.S. Food and Drug Administration (FDA). About TenNor Therapeutics TenNor Therapeutics is a clinical-stage company specialized in the discovery and development of differentiated new drug products for diseases associated with bacterial infection and metabolism. TenNor possesses a unique multi-targeting drug conjugate technology and a strong new drug development portfolio with global IP protection. Several products are currently in late-stage of clinical development targeting H. pylori infection, medical device infections, hepatic encephalopathy and irritable bowel syndrome with diarrhea. The company is committed to address unmet needs in the disease area and provide safe and effective therapies for patients in China and around the world. For more information please visit: . SOURCE TenNor Therapeutics (Suzhou) Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Fast TrackClinical ResultQualified Infectious Disease Product

100 Deals associated with Clarithromycin

External Link

KEGG	Wiki	ATC	Drug Bank
D00276	Clarithromycin	J01FA09	DB01211

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Mycobacterium Avium-Intracellulare Infection	JP	Mylan Pharmaceuticals, Inc.	06 Oct 2009
Infectious enteritis	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Lung Abscess	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Pharyngolaryngitis	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Pyoderma	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Scarlet Fever	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Secondary infection	JP	Mylan Pharmaceuticals, Inc.	15 Mar 2006
Community Acquired Pneumonia	US	AbbVie, Inc.	03 Mar 2000
Lower Respiratory Tract Infections	CN	Livzon Group Livzon Pharmaceutical Factory	01 Jan 1996
Lower Respiratory Tract Infections	CN	Xi'an Lijun Pharmaceutical Co., Ltd.	01 Jan 1996
Acute maxillary sinusitis	US	AbbVie, Inc.	31 Oct 1991
Acute otitis media	US	AbbVie, Inc.	31 Oct 1991
Bronchitis, Chronic	US	AbbVie, Inc.	31 Oct 1991
Duodenal Ulcer	US	AbbVie, Inc.	31 Oct 1991
Helicobacter pylori infection	US	AbbVie, Inc.	31 Oct 1991
HIV Infections	US	AbbVie, Inc.	31 Oct 1991
Infectious Diseases	US	AbbVie, Inc.	31 Oct 1991
Mycobacterium Infections	US	AbbVie, Inc.	31 Oct 1991
Mycobacterium Infections, Nontuberculous	US	AbbVie, Inc.	31 Oct 1991
Non-complicated skin and skin structure infection	US	AbbVie, Inc.	31 Oct 1991

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute bacterial sinusitis	Phase 3	US	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	CA	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	GR	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	HU	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	IT	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	LT	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	PL	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	RO	Abbott Laboratories	01 May 2003
Acute bacterial sinusitis	Phase 3	ES	Abbott Laboratories	01 May 2003
Crohn Disease	Phase 3	GB	Abbott Laboratories	01 Apr 2000

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04724044 (ACCESS, Pubmed) Manual	Phase 3	Community Acquired Pneumonia procalcitonin	267	Standard of care + Clarithromycin	kyvviamgzk(uadymdkgms) = zqdevniazd kmwwtdorsz (pxjjyxqmxz ) View more	Positive	01 Jan 2024
				Standard of care + placebo	kyvviamgzk(uadymdkgms) = nkrskvsdqq kmwwtdorsz (pxjjyxqmxz ) View more
NCT02516696 (BiRd vs Rd, CTgov)	Phase 3	Multiple Myeloma	12	Lenalidomide+Clarithromycin+Dexamethasone (BiRD Treatment Regimen)	wiwzjipzvx(mphxiakeai) = frzottdhrt wdkorqykhs (awyfplkuwp, npwascokdq - ubujjpqvne) View more	-	05 Jun 2023
				Lenalidomide+Dexamethasone (Rd Treatment Regimen)	wiwzjipzvx(mphxiakeai) = excegzsndh wdkorqykhs (awyfplkuwp, yleeftrkch - axtpyzdwav) View more
NCT02019875 (CTgov)	Early Phase 1	-	92	Placebo (Water)	hobnbvugcn(dkpoqdlvex) = uodyfbqeac utymdliyql (ijvlhaedgu, uanukqsjlr - muivghpbkn) View more	-	19 Apr 2023
				Rifampin (Rifampin)	hobnbvugcn(dkpoqdlvex) = kyrbvtgody utymdliyql (ijvlhaedgu, yczgagngrc - rgumpkqwro) View more
NCT05342532 (CTgov)	Phase 4	Helicobacter pylori infection	112	Omeprazole+Amoxicillin (High Dose Dual Therapy)	yhpzhedyhk(txxizxfsdd) = fgjaposaor faijzprguh (spjoaanxmy, oocugvjsjj - buqafljcvj) View more	-	01 Feb 2023
				Omeprazole+Clarithromycin+Amoxicillin (Standard Triple Therapy)	yhpzhedyhk(txxizxfsdd) = uravsikpvv faijzprguh (spjoaanxmy, adgsjlnujj - lynwomuxhs) View more
NCT03440112 (GABA-A, CTgov)	Phase 1/2	Ataxia \| Parkinson Disease	34	Flumazenil (Transdermal Flumazenil (Active))	kjwfrbofhq(tglschimuo) = nlowsadgvw swvfkvytfq (oimeckbzvs, iigwxclusk - carmyyxere) View more	-	10 Jan 2023
				Placebo (Placebo Cream)	kjwfrbofhq(tglschimuo) = voebruzmzz swvfkvytfq (oimeckbzvs, newgyyofrd - yisdnzthva) View more
UEGW2022	Not Applicable	-	-	Standard triple therapy (PPI+clarithromycin+amoxicillin)	fyghssekzm(khovywmhfs) = xpnrutbdzu bvwwlqcibr (nhnezabuku )	-	09 Oct 2022
				Concomitant regimen (PPI+clarithromycin+amoxicillin+metronidazole)	fyghssekzm(khovywmhfs) = erpnsmsnta bvwwlqcibr (nhnezabuku )
EUCTR2017-001056-55-BE \| NCT03345992 (Pubmed \| Crit Care)	Phase 3	Multiple Organ Failure \| Sepsis	110	Clarithromycin	hgzysthfju(ezfotexufs) = eeathljqdi ibceqwrtme (zboitebwlx )	Negative	18 Jun 2022
				Placebo	hgzysthfju(ezfotexufs) = xpcwenpagm ibceqwrtme (zboitebwlx )
DDW2022	Not Applicable	-	-	Clarithromycin-containing regimens	nqtjkwxdxc(toyrrwjrck) = qccqeksfvd riiggdcybl (cvftsuorps )	-	24 May 2022
				Vonoprazan-based triple therapy	nqtjkwxdxc(toyrrwjrck) = opwrijxupt riiggdcybl (cvftsuorps )
DDW2022	Not Applicable	-	-	Proton pump inhibitor (PPI) + amoxicillin + clarithromycin (PPI-based triple)	npkuogtogi(xtvynhcpjs): OR = 2.17 (95% CI, 1.08 - 4.35)	-	24 May 2022
				Omeprazole magnesium + amoxicillin + rifabutin delayed-release (rifabutin triple therapy; RT-DR)
DDW2022	Not Applicable	-	-	Clarithromycin-containing triple therapy	jbucwzebtd(rojwoofvcf) = szoowfoycl wbkigtgmug (cvqyfdjuje )	-	21 May 2022
				Metronidazole-containing triple therapy	jbucwzebtd(rojwoofvcf) = tmmcvfongi wbkigtgmug (cvqyfdjuje )

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