The NMPA is also sprinting as the year is coming to an end. In the past November, 4 Class 1 new drugs, 4 blockbuster first generics, 2 Class 3 generic drugs have been approved for marketing (or will soon be approved for marketing), and 2 Class 1 new drugs have been approved new indications.

The marketing application status of 4 Class 1 new drugs changed in November; wherein, Hansoh's flumatinib and Green Valle's GV-971 were approved for marketing, and BeiGene's anti-PD-1 monoclonal antibody tislelizumab and AstraZeneca's anti-PD-L1 monoclonal antibody durvalumab will be approved for marketing soon.

 (Source: CDE, official websites of the companies)

Shanghai Green Valley's Sodium Oligomannurarate Capsules (i.e., GV-971) was approved by the NMPA for marketing on Nov. 2, which is used to treat moderate to mild Alzheimer's disease (AD) and has become the world's first multi-targeting carbohydrate-based innovative drug against AD. Unlike traditional targeted antibody drugs, GV-971 is a marine oligosaccharide molecule extracted from algae and can capture beta amyloid (Aβ) in multiple points, segments and states, inhibit the formation of Aβ fibrils and depolymerize the formed fibrils into nontoxic monomers. See the article "Breaking News! Shanghai Green Valley's Class 1 New Drug for Alzheimer's Disease Conditionally Approved for Marketing and Already Having the Registration Approval!" for the details.

Flumatinib, a Class 1 new drug independently developed by and the 2nd Class 1 new drug approved for marketing of Hansoh, was approved for marketing on Nov. 26. As a second-generation Bcr-Abl tyrosine-kinase inhibitor (TKI), the drug is used to treat chronic myelogenous leukemia and can improve the clinical treatment effects of some imatinib-resistant patients, with good safety and tolerance. See the article "Breaking News! Hansoh's Class 1 New Drug Flumatinib to be Approved for Marketing Soon" for the details.

The marketing application of AstraZeneca's anti-PD-L1 monoclonal antibody durvalumab (trade name: Imfinzi) changed to "Under approval" on Nov. 22, which is expected to be approved for marketing this month. Used to treat inoperable stage III non-small cell lung cancer (NSCLC), durvalumab will become the first anti-PD-L1 monoclonal antibody marketed in China.

3 anti-PD-L1 monoclonal antibodies have so far been approved in the world, separately being Roche's atezolizumab (trade name: Tecentriq), avelumab (trade name: Bavencio) of Merck/Pfizer, and AstraZeneca's durvalumab (trade name: Imfinzi), all of which have not been marketed in China. Wherein, Roche's atezolizumab and AstraZeneca's durvalumab were separately filed the marketing application in Feb. 2019 and Dec. 2018. There are 15 anti-PD-L1 antibodies in clinical development of 15 Chinese enterprises (involving 54 clinical registration numbers), including Sino Biopharmaceutical, Innovent, Kelun, and Hengrui, etc. Wherein, the first echelon being conducted phase 3 clinical trials including Hengrui';s SHR-1316 injection, Sino Biopharmaceutical's TQB2450 injection, CStone Pharmaceuticals’ CS1001, and Alphamab's KN035. See the article "The First Anti-PD-L1 Monoclonal Antibody to be Market in China; Keytruda Approved All the NSCLC Indications in China" for the details.

BeiGene's marketing application for the anti-PD-1 monoclonal antibody tislelizumab changed to the "Under approval" status (acceptance No.: CXSS1800019) on Nov. 29, with the indication being relapsed/refractory classical Hodgkin lymphoma (cHL), which is expected to be approved for marketing in December to become the 4th marketed Chinese-produced anti-PD-1 monoclonal antibody.

4 Chinese-produced anti-PD-1 monoclonal antibodies (Junshi’ toripalimab, Innovent's sintilimab, Hengrui's camrelizumab, and BeiGene's tislelizumab), and 2 imported anti-PD-1 monoclonal antibodies (BMS’ Opdivo and MSD's Keytruda) are now competing in China, however, only sintilimab has entered the national reimbursement drug list (NRDL) of China.

4 blockbuster first generics

The marketing application status of 4 blockbuster first generics changed in November. Wherein, Bio-Thera's first biosimilar of adalimumab, Yabao Pharmaceutical's first generic of alogliptin, and Hengrui's first generic of celecoxib were approved for marketing, and Qilu Pharmaceutical's first generic of bevacizumab will be approved for marketing soon.

(Source: NMPA)

The first adalimumab biosimilar in China from Bio-Thera was approved for marketing on Nov. 13. The original drug adalimumab (trade name: Humira) was approved for marketing in China in 2010 and has now 3 indications approved in China, i.e., rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis; furthermore, its Crohn's disease indication has been completed phase III clinical trial. Humira was included in the List of the Second Batch of Overseas New Drugs Catering to Clinical Urgent Needs by the CDE in May 2019 for treating uveitis. See the article "Breaking News! Bio-Thera Obtaining the Approval to Produce the First Adalimumab Biosimilar in China, with the Market Size to Exceed RMB10 Billion in 2030" for the details.

Alogliptin of Yabao Pharmaceutical was approved for marketing on Nov. 28 to become the first generic of alogliptin in China. As a dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Takeda Pharmaceutical, alogliptin (trade name: Nesina) was approved to enter the Chinese market in 2013. There have been 5 DPP-4 inhibitors marketed in China, separately, sitagliptin, saxagliptin, vildagliptin, alogliptin, and linagliptin, and there have been 2 DPP-4 inhibitor generics marketed in China, separately, Jiangsu Aosaikang's saxagliptin, and vildagliptin of Hansoh and Qilu Pharmaceutical. Yabao Pharmaceutical will produce the first generic of alogliptin in China upon this approval, which will become the 3rd Chinese-produced PDD-4 inhibitor.

Celecoxib of Hengrui was approved for marketing on Nov. 29. As a blockbuster drug in the anti-inflammatory and analgesic area, the original drug celecoxib was developed by Hengrui and entered China in 2012, with the sales exceeding RMB1 billion in 2018. See the article "Hengrui to Produce the First Generic of the Blockbuster Anti-inflammatory Drug Celecoxib in China! Sales of the Original Drug Reaching RMB1 Billion in a Year in China" for more information.

The review status of bevacizumab biosimilar of Qilu Pharmaceutical changed to "Under approval" on Nov. 29, which is expected to be approved for marketing this month to become the first bevacizumab biosimilar in China. Marketed in China in 2010, bevacizumab (trade name: Avastin) has been approved indications including metastatic colorectal cancer and NSCLC, etc. According to the Insight Database, sales of bevacizumab reached about RMB1.5 billion in 2017. Qilu Pharmaceutical and Innovent have previously filed the marketing applications for bevacizumab biosimilar in succession.

2 Class 3 generic drugs

In November, the Class 3 generic drug esketamine hydrochloride of Hengrui was approved for marketing, and the Class 3 generic drug bendamustine hydrochloride of Chia Tai Tianqing will be approved for marketing soon.

(Source: NMPA)

The Class 3 generic drug esketamine hydrochloride applied for by Hengrui was approved for marketing on Nov. 28, which is used for analgesia and sedation in operation.

Ketamine hydrochloride was first developed by Parke-Davis in 1962. After the company was acquired by Pfizer, it continued to develop the S-enantiomer of ketamine: S(+)-ketamine, i.e., esketamine. Esketamine hydrochloride has now been marketed in countries such as Australia, Germany, and the Netherlands, with the trade name Ketanest S. The global sales of esketamine hydrochloride injection were about USD12 million in 2017 according to the IMS Database. The original drug has not been marketed in China, therefore, Hengrui applied for the drug as a new Class 3 drug. See the article "Good News! Hengrui's Class 3 Generic Drug Esketamine Hydrochloride to be Approved for Marketing Soon for the details.

The marketing application of the Class 3 generic drug bendamustine hydrochloride of Chia Tai Tianqing changed to Under approval status on Nov. 21, which is expected to be approved for marketing this month to treat NHL. The global sales of the original drug peaked at USD767 million in 2014. 

2 Class 1 new drugs approved new indications

2 blockbuster new drugs were approved new indications in November, which were separately Chipscreen Biosciences’ chidamide and MSD's Keytruda.

(Source: NMPA)

The 2nd indication of Chipscreen Biosciences’ chidamide was approved on Nov. 28, to treat estrogen receptor (ER) positive advanced breast cancer in combination with exemestane. Its first indication is peripheral T-cell lymphoma (PTCL) that has relapsed or is refractory to at least one systemic chemotherapy and was approved by the NMPA in Dec. 2014. As the first Class 1 new drug approved for marketing based on phase II clinical results in China, chidamide is also the only Chinese-produced drug for PTCL. See the article "Big News! The 2nd Indication of Chipscreen Biosciences’ Chidamide to be Approved Soon" for the details.

A new indication of Keytruda (pembrolizumab) was approved on the same day, which is the first-line treatment of squamous NSCLC in combination with chemotherapy. Keytruda will be the anti-PD-1/L1 monoclonal antibody approved the largest number of indications in China, including the second-line treatment of melanoma, first-line treatment of squamous NSCLC in combination with chemotherapy, first-line treatment of non-squamous NSCLC in combination with chemotherapy, and first-line treatment of PD-L1-positive NSCLC. See the article "Keytruda to be Approved the 4th Indication in China: First-line Treatment of Squamous NSCLC" for the details.

Furthermore, BeiGene's zanubrutinib was approved by the FDA for marketing also in November and is expected to be approved by the NMPA for marketing soon.

About  the Author:    

Caicai, a Master of Pharmacy from Shanghai Jiaotong University, used to work in the Institute of Science and Technical Information. Currently as a practitioner in the drug surveillance system, she is good at interpreting industry regulations, pharmaceutical research developments, etc.

Editor's Note:

To become a freelance writer of En-CPhI.CN,

welcome to send your CV and sample works to us,

Email: Julia.Zhang@ubmsinoexpo.com.