2023.08Products UpdateHengrui's PD-1 camrelizumab+apatinib under marketing review for liver cancerin USChina-based Jiangsu Hengrui Medicine Co., Ltd (600276.SH) announced that a Biologic License Application (BLA) for its programmed death-1 (PD-1) monoclonal antibody (mAb) camrelizumab combined with small-molecule targeted cancer therapy apatinib as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC) has been accepted for review by the US Food and Drug Administration (FDA).The filing is based on the SHR-1210-III-310 study, a global, multicenter Phase III clinical study showing the combo\delivered significant survival benefits and tolerable safety with 22.1 months of median overall survival (OS). The study is billed as the first and currently only successful Phase III study for the combination of an immunotherapy and small molecule tyrosine kinase inhibitor (TKI) in HCC.Camrelizumab was first approved in China in May 2019, and has since chalked up nine indication approvals in total including liver cancer, lung cancer, esophageal squamous cell carcinoma (ESCC), nasopharyngeal cancer (NPC), and lymphoma. Apatinib, meanwhile, is a selective vascular endothelial growth factor receptor-2 (VEGFR-2) TKI. It was first approved in 2014 for advanced GC/GEJ that has progressed or relapsed after treatment with at least two systemic chemotherapies. It has since been approved for use in advanced hepatocellular carcinoma in patients unresponsive to or intolerable of first-line or later systemic therapies in January 2021 and first-line treatment of HCC combined with camrelizumab in January this year.(Source: static.sse.com.cn; 2023-08-01) Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleInnovent’s tafolecimab becomes first home-grown PCSK-9 inhibitor in ChinaChina-based Innovent Biologics Inc. (HKEX: 01801) announced receiving market approval from the National Medical Products Administration for its tafolecimab (IBI306), a recombinant fully human anti-PCSK-9 monoclonal antibody (mAb). The approved indication is for primary hypercholesterolemia (including heterozygous familial and non-familial hypercholesterolemia) and mixed dyslipidemia.Innovent's tafolecimab, the first home-grown PSCK9 inhibitor to reach the market, is an lgG2 mAb that can specifically bind to PCSK-9 and reduce LDL-C levels by inhibiting PCSK-9-mediated low-density lipoprotein receptor (LDL-R) endocytosis, subsequently enhancing the clearance of LDL-C. The approval is based on the results of three Phase III regulatory studies, which involved three approved medication regimes, 150 mg Q2W, 450 mg Q4W and 600 mg Q6W. They all demonstrated the drug’s ability to reduce levels of LDL-C, total cholesterol (TC), non-high-density lipoprotein cholesterol (non HDL-C), apolipoprotein B (ApoB), and lipoprotein a.(Source: mp.weixin.qq.com; 2023-08-17)Immunofoco’s SNR-CAR-T cell therapyawarded ODD in USImmunofoco, a cell therapy developer based in Suzhou, announced receiving orphan drug designation(ODD) from the US Food and Drug Administration for its next-generation autologous CAR-T therapy IMC008 in gastric cancer.IMC008 is based on Immunofoco’s Synthetic Natural killer Receptor (SNR) technology platform, which not only targets specific antigens through dual recognition and functional enhancement mechanisms, but also expands the antigen recognition range of CAR-T cells through SNR receptors, effectively solving the challenges posed by tumor antigen heterogeneity. At the same time, SNR signals also have a synergistic effect with CAR signals, further enhancing the proportion of memory T cells in CAR-T cells, enhancing the expansion and tumor infiltration of CAR-T cells in animals, and enhancing the ability to clear antigen heterogeneous tumor tissue.(Source: mp.weixin.qq.com; 2023-08-17)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleLuye’s long-acting risperidonecommercialized in USChina-based Luye Pharma Group (2186.HK) announced official commercial operation of its Rykindo (risperidone) extended-release injectable suspension in the United States. Rykindo, developed by Luye Pharma on its microsphere technology platform, is administered via intramuscular injection once every two weeks and delivers the active ingredient, risperidone, via long-acting and extended-release microsphere technology.Rykindo was approved for marketing in the US in January this year for the treatment of schizophrenia in adults and as a monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults. The drug, waved through in China in 2021, is billed as the first Chinese central nervous system (CNS) drug approved in the US and first complex preparation developed by a company from Chinese mainland that was approved via FDA’s 505(b)(2) pathway.(Source: mp.weixin.qq.com; 2023-08-18)HutchMed’s savolitinib awarded BTD status for new indicationHutchMed (China) Ltd (Nasdaq/AIM:HCM; HKEX:0013) announced that its Orpathys (savolitinib), a MET inhibitor under co-development with AstraZeneca and approved in China on July 12, is to be awarded breakthrough therapy designation (BTD) in China. The BTD status is focused on savolitinib's use as a third-line treatment for locally advanced or metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction with MET gene amplification.Orpathys is HutchMed's third product to enter the market, and China's first mesenchymal-epithelial transformation factor (MET) inhibitor to be approved as a treatment for non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations who have progressed after chemotherapy or unsuited to systemic therapy. The drug entered into the National Reimbursement Drug List (NRDL) earlier this year via price negotiations.(Source: cde.org.cn; 2023-08-18)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleAZ’s Forxiga adds new Chinaheart failure indicationUK-based major AstraZeneca plc (Nasdaq: AZN) revealed a new indication approval in China for the firm’s SGLT-2 inhibitor Forxiga (dapagliflozin). The National Medical Products Administration (NMPA) gave the nod for Forxiga to reduce the risk of cardiovascular death, hospitalization for heart failure (HF), or urgent HF visits in adults with symptomatic chronic HF.Forxiga was already approved in China to treat HF patients with reduced ejection fraction (HFrEF), so the new approval expands its use to all HF patients regardless of ejection fraction status. The molecule is an SGLT2 inhibitor, and the first to be approved in China when nodded for use in controlling type 2 diabetes in March 2017. The HFrEF indication was added in February 2021, while the drug has been reimbursed nationally since 2019.As shown in the DELIVER and DAPA-HF Phase III trials, Forxiga is the first HF medication to demonstrate a mortality benefit across the full ejection fraction range. HF – when the heart is not capable of pumping sufficient blood around the body – occurs in about 4.5 million patients in China each year. Around half of HF patients die within five years of diagnosis.Notably the approval may provide AstraZeneca with some moat against generic competitors in China. The UK giant recently lost out in a 4.1 patent linkage challenge, with four generics versions of the drug currently on the market in China. Forxiga was AZ’s top-selling drug in 2022 with USD 4.386 billion in sales, growing at 56% year-on-year.(Source: astrazeneca.com; 2023-08-21)Novartis’s first-in-class anti-cholesterolsiNRA drug Leqvio wins first China nodSwiss giant Novartis announced its cholesterol-lowering drug Leqvio (inclisiran) has been approved by the National Medical Products Administration to be used as an adjunct treatment with diet for the treatment of adult patients with primary hypercholesterolemia (heterozygous familial and non familial) or mixed type dyslipidemia. The approval covers use combined with statins, or combined with statins plus other lipid-lowering therapies, in patients who still cannot achieve low density lipoprotein cholesterol (LDL-C) targets after receiving the maximum tolerable dose of statins, and in patients who are intolerant or contraindicated to statins, used alone or in combination with other lipid-lowering therapies.Inclisiran is the world’s first and currently only siRNA drug to lower LDL-C. The molecule blocks the PCSK9 synthesis that causes an increase in LDL-C from the source, thereby stably reducing LDL-C levels in the long term. The drug features a convenient dose schedule, requiring only two injections per year to effectively reduce LDL-C levels following a first booster injection three months after the first injection. Clinical studies have shown that for patients who still cannot meet LDL-C standards after treatment with the maximum tolerable dose of statins, inclisiran can reduce their LDL-C by up to 54%. Five years of clinical research data show that inclisiran has sustained efficacy and good safety tolerance.(Source: novartis.com.cn; 2023-08-23)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleGSK posts 100% efficacy data for Shingrix in Phase IV China studyUK-based major GSK plc (LSE/NYSE: GSK) released efficacy data for its shingles vaccine Shingrix (recombinant zoster vaccine; RZV) in Chinese patients. The Phase IV post-marketing ZOSTER-076 trial was carried out in China with nearly 6,000 participants aged 50 and over. With participants randomized 1:1 receiving either vaccine or placebo, no cases of shingles were reported in those who received RZV, compared to 31 cases in the placebo arm, equating to a 100% efficacy rate.The results are consistent with the global pivotal Phase III trials ZOE-50 and ZOE-70, which showed Shingrix’s efficacy to be 97% over a follow-up period of approximately four years.Shingles is caused by a reactivation of the varicella-zoster virus (VZV), which lies dormant in the majority of people aged 50 and over, who become increasingly at risk of developing shingles as they age and the immune system wanes. Around 6 million shingles cases are diagnosed in China annually.Shingrix was first approved in the US in 2017, and arrived in China in 2020. The vaccine is an important part of GSK’s growth strategy for the China market, with global sales in 2022 at GBP 2.96 billion (USD 3.7 billion), growing at 60% year-on-year with China identified as an important driver.(Source: gsk.com; 2023-08-24)Dizal's sunvozertinib eligible to treat EGFR Exon20ins NSCLC in ChinaChina-based Dizal Pharmaceutical Co., Ltd (SHEX: 688192) announced receiving market approval from the National Medical Products Administration (NMPA) for its next-generation epidermal growth factor receptor (EGFR) inhibitor sunvozertinib. The novel targeted therapy can now be used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor 20 exon insertion (EGFR Exon20ins) mutation in patients previously treated with platinum chemotherapy or intolerant of platinum. It is touted as the first and currently only home-grown Category 1 drug with breakthrough therapy designation (BTD) statuses in China and the US, alongside a priority review status in the former.The approval is based on the single-arm, multi-center Phase II regulatory WU-KONG6 study, which showed that in the efficacy analysis population of 97 patients receiving sunvozertinib, the objective response rate (ORR) confirmed by IRC reached 60.8%, with safety similar to traditional EGFR TKIs. Additionally, the overall tolerability was good, and clinical management could be restored.(Source: prnasia.com; 2023-08-24)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleNovartis finally loses patent protectionin China for EntrestoChina-based Nanjing F&S Pharmatech Co., Ltd announced receiving market approval from the National Medical Products Administration (NMPA) for its generic version of Swiss giant Novartis’s heart failure therapy Entresto (sacubitril, valsartan). Nanjing F&S's version is an in-house developed crystal form of the molecule and has passed China's bioequivalence (BE) clinical testing. The approval is both the first generic to be approved in China and the first to successfully challenge Entresto globally.Entresto, a breakthrough therapy for chronic heart failure, was first approved in China in 2017, nodded to treat primary hypertension in June 2021. The drug generated close to RMB 3 billion (USD 415 million) in sales in China last year.The Orange Book indicates that there are 6 patents relating to the drug registered in China, all concerning "Pharmaceutical composition containing valsartan and NEP inhibitor" (Patent No.: ZL201110029600.7). That patent was declared invalid in April 2017, a decision later reconfirmed by CNIPA in 2018 and confirmed by the People's Court in 2019. This was not sufficient to allow generics on to the market, however, and in 2021 CNIPA confirmed the drug's core patent remained valid. The 20-year patent protection period for both of Entresto's core patents were meant to expire on November 8, 2026. The approval of F&S Pharma’s generic version allows the Chinese patients with heart failure and hypertension to access a high-quality copy drug three years in advance.(Source: mp.weixin.qq.com; 2023-08-24)CSPC Pharma’s generic Entresto secondto be approved in ChinaChina-based CSPC Pharmaceutical Group Ltd (HKEX: 1093) announced its generic version of Swiss giant Novartis’s heart failure therapy Entresto (sacubitril, valsartan) has been approved for marketing in China, where its compatriot firm Nanjing F&S Pharmatech Co., Ltd’s version took the first-mover advantage on the same day. Said product can now be used to treat adult patients with chronic heart failure (NYHA II-IV grade, LVEF ≤40%) with reduced ejection fraction, reducing the risk of cardiovascular death and hospitalization for heart failure and primary hypertension.Entresto, a breakthrough therapy for chronic heart failure, was first approved in China in 2017, nodded to treat primary hypertension in June 2021. The drug generated close to RMB 3 billion (USD 415 million) in sales in China last year.The Orange Book indicates that there are 6 patents relating to the drug registered in China, all concerning "Pharmaceutical composition containing valsartan and NEP inhibitor" (Patent No.: ZL201110029600.7). That patent was declared invalid in April 2017, a decision later reconfirmed by CNIPA in 2018 and confirmed by the People's Court in 2019. This was not sufficient to allow generics on to the market, however, and in 2021 CNIPA confirmed the drug's core patent remained valid. The 20-year patent protection period for both of Entresto's core patents were meant to expire on November 8, 2026.(Source: mp.weixin.qq.com; 2023-08-25)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleNovartis defends its heart failure therapyEntresto's exclusivityGeneric versions of Swiss giant Novartis's heart failure therapy Entresto (sacubitril, valsartan) won market approvals on August 24, 2023. The two awards went to Chinese firms Nanjing F&S Pharmatech Co., Ltd and CSPC Pharmaceutical Group Ltd (HKEX: 1093). That triggered a statement from Novartis on August 28, 2023, stating that Entresto's active ingredients, sacubitril+valsartan, remain under protection of patents No.ZL200680001733.0 and ZL201210191052.2 in China, both valid through November 2026.According to Article 11 of the Chinese Patent Law, no enterprise or individual shall manufacture, use, promise to sell (including applying for online listing, participating in bidding, etc.), sell, or import products that fall within the scope of patent protection before the expiration of the above-mentioned patent period, unless authorized by Novartis. Otherwise, it will constitute patent infringement. Novartis reserves the right to claim its patent rights against infringing imitations from relevant judicial and/or administrative authorities.The Orange Book indicates that there are 6 patents relating to the drug registered in China, all concerning "Pharmaceutical composition containing valsartan and NEP inhibitor" (Patent No.: ZL201110029600.7). That patent was declared invalid in April 2017, a decision later reconfirmed by CNIPA in 2018 and confirmed by the People's Court in 2019. This was not sufficient to allow generics on to the market, however, and in 2021 CNIPA confirmed the drug's core patent remained valid. The 20-year patent protection period for both of Entresto's core patents were meant to expire on November 8, 2026.(Source: mp.weixin.qq.com; 2023-08-28)BI seeks approval for three Phase III studiesfor obesity therapy survodutide in ChinaGermany-based Boehringer Ingelheim announced three IND filings for regulatory Phase III global multi-center studies in China for its survodutide, a novel glucagon receptor/GLP-1 receptor dual agonist. The drug is being co-developed with Zealand Pharma.BI previously released data for survodutide from a dose-exploration Phase II study in overweight or obese individuals. That showed that after a 46-week period of survodutide treatment, patients enjoyed up to a 19% weight reduction, with Chinese patients also participating. Another Phase II study evaluated the therapeutic effect of survodutide in adult patients with NASH and liver fibrosis (F1/F2/F3) (regardless of whether they have type 2 diabetes or not), an indication which was awarded fast-track status from the US FDA.(Source: prnasia.com; 2023-08-29)Subscribe to GBI SOURCEa global pharma database covers the entire product lifecycleProduct developments summary,August 2023近期报告H1'23 MNCs Performance in China Market and Policy HighlightsFuture! Untapped potential of galectins’ role in human disease?Patent Linkage Litigation in China: A Two-year ReviewDeal Monitor H1’23: In-licensing bottoms out as VC warms up