Evocalcet and Capmatinib Launched in China; ASO Drug AHB-137 Shows Promising Data for Functional Cure of Hepatitis B

Jun 13, 2024 20:31 CST Updated 20:31

AusperBio

Biological Vaccine and Nucleic Acid Drug Developer

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AusperBio: Disclosure of Latest Research Progress on Potential "Best-in-Class" ASO Drug AHB-137, Showing Promise for Functional Cure of Hepatitis B

Recently, AusperBio disclosed the latest research progress of its antisense oligonucleotide (ASO) drug AHB-137 at the 2024 European Association for the Study of the Liver (2024 EASL) Annual Meeting. The updates include the Phase I/IIa clinical trial (AB-10-8002) conducted among subjects in mainland China and the international multicenter Phase I clinical trial (AB-10-8001). Currently, the AB-10-8001 trial remains blinded, while the AB-10-8002 trial has been unblinded.

AHB-137 is an antisense oligonucleotide (ASO) developed by AusperBio Therapeutics and Ausper Biopharma, a clinical-stage biopharmaceutical company, for the treatment of chronic hepatitis B (CHB). It has demonstrated good preclinical safety and strong antiviral activity and is currently in Phase I/lla clinical development.

LBP-019: Safety and Preliminary Antiviral Activity Data from Healthy Volunteers (HV) and Chronic Hepatitis B (CHB) Subjects in Two Ongoing Phase I/IIa Clinical Studies of AHB-137. The AB-10-8001 study enrolled 40 HVs into four single ascending dose groups (SAD, 6:2, up to a maximum dose of 450mg) and one multiple-dose group (MD, 6:2, 300mg administered on Days 1, 4, 8, 15, and 22 for a total of five doses). Across two studies, 52 hepatitis B e antigen (HBeAg)-negative CHB subjects receiving stable nucleoside analog (NA) therapy were included, with 44 subjects (14 from AB-10-8001, 30 from AB-10-8002) receiving up to six doses of 150mg or 300mg subcutaneous injections of AHB-137 within four weeks and completing at least the D29 visit. Baseline hepatitis B surface antigen (HBsAg) levels were below 1,000 IU/mL in 32 CHB subjects, while 12 CHB subjects (HighS subjects) had baseline HBsAg levels between 1,000 and 10,000 IU/mL. As of April 8, 2024, 40 HVs and 13 CHB subjects have successfully completed the study, with 31 CHB subjects currently in follow-up. The enrolled CHB subjects are aged between 26 and 63 years, predominantly male (82%) and Asian (91%). The AB-10-8001 clinical trial remains blinded, while the AB-10-8002 clinical trial has been unblinded.

Safety Results: In the AB-10-8001 clinical trial, no serious adverse events (SAEs) related to the study drug were reported, and no adverse events (AEs) led to subject discontinuation of dosage, dose reduction, early withdrawal from the study, or death. Treatment-related adverse events (TRAEs) were reported by 72.5% (29/40) of HVs and 78.6% (11/14) of CHB subjects. With the exception of one grade 3 injection site erythema, all TRAEs were grade 1 or 2. The most common TRAEs (occurring in more than one subject) were injection site reactions, headache, nausea, fever, and myalgia.

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AstraZeneca's Third-Generation EGFR Inhibitor "Osimertinib" Submits New Lung Cancer Indication in the U.S.

On June 10, AstraZeneca announced that the U.S. FDA had accepted and granted priority review to a supplemental New Drug Application (sNDA) for Tagrisso (osimertinib) to treat patients with unresectable EGFR-mutated (exon 19 deletion or exon 21 (L858R) mutation) stage III non-small cell lung cancer (NSCLC) following chemoradiation therapy (CRT). The FDA is expected to make a regulatory decision in the fourth quarter of this year. Osimertinib, a third-generation EGFR inhibitor developed by AstraZeneca, was first approved in the United States in November 2015. To date, osimertinib has been approved for four indications. This sNDA is primarily based on positive results from the Phase III LAURA trial. The results showed that the median progression-free survival (PFS) was significantly longer in the osimertinib group compared to the placebo group (39.1 vs. 5.6 months, HR=0.16, P<0.001); at 12 months, 74% of patients in the osimertinib group were alive without disease progression, compared to 22% in the placebo group; at 36 months, 84% and 74% of patients were alive in the osimertinib and placebo groups, respectively (HR=0.81, P=0.53, data maturity 20%). In terms of safety, the incidence of grade 3 or higher adverse events was 35% in the osimertinib group and 12% in the placebo group. Additionally, radiation pneumonitis (mainly grade 1-2) was reported in 48% of patients in the osimertinib group, compared to 38% in the placebo group. No new safety concerns were identified.

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Bayer's Oral HER2 Inhibitor BAY2927088 Initiates Head-to-Head Phase III Clinical Trial with K Drug for Non-Small Cell Lung Cancer Treatment

Information from the ClinicalTrial platform shows that on June 11, Bayer registered a Phase III head-to-head clinical trial (NCT06452277) of BAY 2927088 versus Keytruda (Pembrolizumab, Keytruda) in patients with locally advanced or metastatic NSCLC harboring HER2-activating mutations. BAY 2927088 is a tyrosine kinase inhibitor being developed by Bayer as a potential novel targeted therapy for non-small cell lung cancer (NSCLC) patients with HER2-activating mutations. In February this year, BAY 2927088 received Breakthrough Therapy Designation from the U.S. FDA. Recently, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) granted BAY 2927088 Breakthrough Therapy Designation for the treatment of adult patients with unresectable or metastatic NSCLC who carry HER2-activating mutations and have previously received one systemic therapy. In this head-to-head study, Bayer plans to recruit 278 patients aged 18 years and older with HER2-activating mutations and locally advanced or metastatic NSCLC across multiple centers globally, including Beijing Cancer Hospital, Beijing Hospital, Shandong Cancer Hospital affiliated with Shandong University, Shanghai Chest Hospital affiliated with Shanghai Jiao Tong University, and Nanjing Drum Tower Hospital in mainland China. Eligible patients will be randomly assigned to either the BAY 2927088 group or the standard treatment group (Keytruda plus platinum-based chemotherapy). The BAY 2927088 group will receive 20 mg orally twice daily until disease progression, unacceptable toxicity, or any other withdrawal criteria are met. The primary endpoint of the study is progression-free survival (PFS), determined by a blinded independent review committee (BICR) based on RECIST 1.1 criteria, with a maximum follow-up of two years. Secondary endpoints include overall survival (OS), objective response rate (ORR), and PFS over a maximum period of four years.

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Regeneron/Sanofi's IL-6R-targeted monoclonal antibody Sarilumab Receives FDA Approval Again for the Treatment of Juvenile Idiopathic Arthritis

On June 12, Regeneron Pharmaceuticals announced that the U.S. FDA had approved Kevzara (sarilumab), co-developed with Sanofi, for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients weighing 63 kilograms or more. This is a type of arthritis that affects multiple joints simultaneously. Kevzara, a humanized monoclonal antibody co-developed by Regeneron and Sanofi, binds to the interleukin-6 (IL-6) receptor, thereby inhibiting its mediated signaling pathway. In the human body, interleukin-6 is a cytokine that plays a significant role in inflammatory responses. When its expression levels remain higher than normal over a prolonged period, it causes a series of inflammatory reactions, including those associated with rheumatoid arthritis. The U.S. FDA's approval of this therapy for treating pJIA patients is based on sufficient and well-controlled trial results, pharmacokinetic data from adult rheumatoid arthritis patients, as well as pharmacokinetic, pharmacodynamic, dose-finding, and safety studies in pediatric pJIA patients. Compared with rheumatoid arthritis patients, no new adverse reactions or safety issues were identified in pJIA patients. The most common adverse drug reactions in pJIA patients include nasopharyngitis, neutropenia, upper respiratory tract infections, and injection site erythema.

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Kyowa Kirin's New Generation Calcimimetic "Evocalcet" Approved for Marketing in China, for the Treatment of Hyperparathyroidism

On June 12, the official website of the National Medical Products Administration (NMPA) announced that Kyowa Kirin's Evocalcet tablets have been approved for marketing in China. The drug is indicated for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease. Evocalcet is a new-generation oral calcium-sensing receptor agonist (calcimimetic), which was first approved in Japan in March 2018 for the treatment of SHPT in chronic kidney disease (CKD) patients on maintenance dialysis. In December 2019, Evocalcet received approval for a new indication to treat hypercalcemia associated with parathyroid carcinoma or inoperable or postoperative recurrent primary hyperparathyroidism. According to the China Drug Trial Registration and Information Disclosure Platform, Kyowa Kirin has completed an international multicenter Phase 3 clinical study in China, evaluating Evocalcet for the treatment of SHPT in CKD patients undergoing maintenance dialysis. The trial aimed to assess the efficacy and safety of daily oral Evocalcet over 52 weeks in SHPT patients receiving hemodialysis, using Cinacalcet Hydrochloride as the active comparator in a randomized, double-blind, self-dose-adjusting, parallel-group design. Globally, Evocalcet was approved in Japan in 2018 for treating SHPT in maintenance dialysis patients. Results from a single-center longitudinal study conducted in Japan showed that the product significantly reduced intact parathyroid hormone (iPTH) levels in peritoneal dialysis SHPT patients. At week 16, iPTH levels were significantly decreased compared to baseline (346 pg/ml vs 258 pg/ml) and maintained until week 32. Additionally, gastrointestinal adverse reactions were significantly reduced during the trial.

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Novartis' c-Met Inhibitor Capmatinib Approved for Marketing in China to Treat Non-Small Cell Lung Cancer

On June 12, Novartis announced that the marketing application for capmatinib tablets had been officially approved by the National Medical Products Administration (NMPA) of China. It is indicated for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping mutations (METex14 mutations) who have not received systemic treatment. Capmatinib is an orally administered, selective, ATP-competitive c-Met kinase inhibitor that exhibits high selectivity for the c-Met target. It effectively inhibits c-Met-dependent tumor cell proliferation and migration and induces apoptosis to achieve anti-tumor activity. The drug was initially discovered by Incyte, and Novartis obtained its development and commercialization license in 2009. According to an earlier press release from Novartis, capmatinib is the first targeted therapy approved by the U.S. FDA for the treatment of METex14 skipping mutation-positive metastatic NSCLC across all lines of therapy. Previously, this product has been approved for marketing in the United States, Japan, the European Union, and other countries/regions. The clinical research data supporting the approval of capmatinib hydrochloride tablets in China include the global multicenter clinical trial GeoMETry mono-1 and the registration clinical study GeoMETry-C conducted in the Chinese population. The GeoMETry mono-1 study showed that, according to assessments by a blinded independent review committee, capmatinib achieved an objective response rate (ORR) of 68.3% and a disease control rate (DCR) of 98.3% in treatment-naïve patients with advanced NSCLC harboring METex14 skipping mutations, with a median overall survival (OS) of 25.5 months. The China-specific GeoMETry-C clinical study demonstrated that, as of the data cutoff date of November 30, 2022, the ORR of capmatinib as a first-line treatment for METex14 skipping mutation-positive advanced NSCLC was 53.3% (assessed by a blinded independent review committee) and 60% (investigator-assessed), consistent with globally observed data. Additionally, a complete intracranial response rate (iCR) of 50% was observed in patients with brain metastases. Regarding safety, the overall incidence of adverse reactions in Chinese patients was similar to that in the global population.

Source: Yaorong Cloud New Drug Notes, for more new drug content, please follow Yaorong Cloud New Drug Notes.

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