China Approves 14th PD-1 Inhibitor; Livzon Submits New Indication for Its ¥3B Blockbuster, with Updates from Lepu Bio and Humanwell

Highlights of the Week

1. The 14th PD-1 in China has been approved! From Lepu Biopharma

2. Humanwell Healthcare's "Remimazolam" Approved for New Indication

3. Livzon Pharmaceutical Core Product Iprazol Applies for New Indications

4. BMS Submits First TYK2 Inhibitor for Market Approval in China

This week (July 15 to July 22), Lepu Biopharma's PD-1 monoclonal antibody was approved for marketing, marking the 14th such drug in China; Humanwell Healthcare’s new anesthetic "Remimazolam" received approval for a new indication; the PPI inhibitor injection of Aipulaprazole Sodium submitted a new indication application for marketing; several blockbuster drugs reported new progress in production. More updates are as follows:

China's Review and Approval · New Developments

This week, the CDE updated the production status of 26 acceptance numbers (22 varieties). Among them, Humanwell Healthcare's Remimazolam Besylate for Injection and Lepu Biopharma's Putelizumab Injection have drawn significant attention. More updates are as follows:

Data Source: Pharmcube Data

The 14th PD-1 in China Approved! From Lepu Biopharma

On July 22, the anti-PD-1 monoclonal antibody developed by Lepu Biopharma – Prolca™ (Prolgolimab Injection) – was granted conditional approval by the NMPA for marketing. The indication is: for the treatment of patients with advanced solid tumors characterized by high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) who have failed first-line or higher systemic treatments. Data from Pharma Intelligence shows that this is the 14th PD-1/PD-L1 monoclonal antibody approved in China.

Approved Indications for PD-1/PD-L1 Monoclonal Antibodies Already on the Market in China

Data source: Yaoke Data

According to the news release from Lepu Biopharma, Putelizumab can bind with high affinity to PD-1, restoring immune cells' ability to kill cancer cells by blocking the binding of PD-1 with its ligands PD-L1 and PD-L2. Putelizumab Injection uses innovative molecular design to extend its half-life, demonstrating potent clinical anti-tumor activity and good safety.

This approval is mainly based on the objective response rate (ORR) from a multicenter, open-label, Phase II clinical study. As of December 4, 2021, the ORR was 49.0% (95% CI: 38.86%, 59.20%); in the subgroup of colorectal cancer patients who had failed prior treatment with three drugs (fluorouracil, oxaliplatin, and irinotecan), the ORR was 50.0% (95% CI: 31.30%, 68.70%). Previously, the marketing application for this indication was granted priority review by the CDE.

In addition, the marketing application for Prolitumab as a second-line treatment for melanoma was officially accepted by the CDE in July 2021 and is currently in the review and approval stage. In terms of internationalization, IND approval from the U.S. FDA for Prolitumab in treating advanced solid tumors was obtained in January 2022.

Humanwell's "Remimazolam" Approved for New Indication

On July 22, Humanwell Healthcare's new anesthetic drug "Remimazolam Besylate for Injection" received NMPA approval for a new indication. This is the third approved indication for the product, with the presumed indication being: sedation for bronchoscopy procedures.

Remimazolam Besylate for Injection, jointly developed by Yichang Humanwell and German PAION, is a new type of ultra-short-acting intravenous benzodiazepine sedative. As an ultra-short-acting GABAa receptor agonist, it is water-soluble and has a short elimination half-life. In July 2020, the product was approved for marketing in China for the first time for sedation during colonoscopy. In March 2022, it expanded its indications to include induction and maintenance of general anesthesia.

China's Review and Approval · New Acceptance

This issue of the CDE added 57 new production acceptance numbers, covering 43 varieties. Notably, Ascentage Pharma/Innovent Biologics' Olverembatinib Tablets, Livzon Pharmaceutical's Injectable Esomeprazole Sodium, and Bristol-Myers Squibb's Deucravacitinib Tablets have gained significant attention. For more updates, see the table below:

Data Source: Pharmcube Data

Ascentage Pharma's "Olverembatinib" Marketing Application for Resistant CML Accepted

PharmCube data shows that the new drug marketing application (Class 2.4) for Olverembatinib (brand name: Nylc), submitted by Ascentage Pharma, has been accepted by the CDE and included in the priority review process for the treatment of chronic myeloid leukemia in the chronic phase (CML-CP) patients who are resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs).

Olverabatinib is an original Class 1 new drug developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor and the first third-generation BCR-ABL-targeted drug for treating resistant chronic myeloid leukemia (CML) to be approved in China, having received support from the national "Major New Drug Development" program. In November 2021, the NMPA granted conditional approval to the marketing application of Olverabatinib (trade name: Nulast®) through the priority review and approval process. It is indicated for the treatment of adult patients with chronic-phase (CML-CP) or accelerated-phase (CML-AP) chronic myeloid leukemia who are resistant to any tyrosine kinase inhibitor and have been diagnosed with the T315I mutation using a fully validated detection method.

This acceptance and inclusion in the priority review was based on an open, randomized controlled confirmatory pivotal Phase II registration study (HQP1351CC203 study). In March 2021, the CDE had already designated Olverad® as a breakthrough therapy based on this study.

In addition, Orelabrutinib has received one Fast Track designation from the U.S. Food and Drug Administration (FDA); three FDA Orphan Drug designations with indications for CML, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML); and one EU Orphan Drug designation from the European Medicines Agency (EMA) for the indication of CML.

In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics, Inc. (1801.HK) reached a strategic cooperation for the co-development and co-commercialization promotion of Olverembatinib in the Chinese market.

Livzon Pharmaceutical's Core Product Esomeprazole Files for New Indications

PharmCube data shows that Livzon Pharmaceutical has submitted a new drug application for the listing of Sodium Eprazolin for Injection (Type 2.4), which has been accepted by the CDE. The speculated indication is for the prevention of stress ulcer bleeding in critically ill patients.

Ilaprazole belongs to the irreversible proton pump inhibitors (PPI) and is a core product of Livzon Group. Currently, there are two generations with six types of PPI drugs available in the market: The first generation includes Omeprazole, Lansoprazole, and Pantoprazole; the second generation includes Rabeprazole, Esomeprazole, and Ilaprazole. Among the six major PPI drugs, Ilaprazole is the only one independently developed by a Chinese pharmaceutical company (Livzon Group) and remains an exclusive product in China.

Livzon Group once stated in a press release that ilaprazole has obvious advantages compared with similar PPI drugs, such as small dosage, rapid onset, long-lasting effect, high safety, and unique metabolism mechanism without individual differences. Sodium Ilaprazole for Injection was approved for marketing in January 2018, with the function/main indication: bleeding of peptic ulcer, and was first included in the "Medical Insurance Catalog" through negotiation in November 2019. The sales growth rate in the past three years has reached triple digits.

In 2021, the sales revenue of the Aipulazol series (oral enteric-coated tablets + injection) was approximately 3 billion yuan. In the first quarter of this year, it is estimated that the sales volume of Aipulazol injections will increase by more than 50% year-on-year, and the sales volume of tablets will increase by more than 30% year-on-year. The launch of new indications is expected to continue driving growth.

BMS's First TYK2 Inhibitor Submitted for Marketing Approval in China

Recently, the marketing authorization application for deucravacitinib tablets (BMS-986165), a Class 1 new chemical drug submitted by Bristol-Myers Squibb, has been accepted by the CDE. The speculated indication is moderate to severe plaque psoriasis.

Deucravacitinib is the first orally available, selective allosteric inhibitor of tyrosine kinase 2 (TYK2) independently developed by Bristol-Myers Squibb. Unlike known JAK inhibitors, deucravacitinib selectively binds to the pseudokinase domain (JH2) of TYK2 and inhibits the activity of TYK2 kinase through an allosteric mechanism, with weaker inhibitory effects on JAK1, JAK2, and JAK3, which would effectively reduce adverse events caused by the inhibition of JAK1, JAK2, and JAK3. Previously, the FDA accepted the application for deucravacitinib to treat adults with moderate to severe plaque psoriasis, with a PDUFA date set for September 10, 2022. If approved, deucravacitinib will become the first TYK2 inhibitor to be marketed.

Data Source: Pharma Intelligence Data, Corporate Announcements, and Other Publicly Available Online Data

Source: Pharma Intelligence Network, corporate announcements, and other publicly available online information

Editor: Liuli

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