This week, the EU officially released the eagerly anticipated final revision of its GMP Annex 1 for sterile drug products. The news review of this week is from August 22 to 26, covering a total of 20 pieces of information on drug review, R&D, business, and policy.

Drug Review

NMPA – Marketing

[Application]

1. On August 23, the CDE official website revealed that the marketing application for the new indication of BeiGene Tislelizumab (brand name: Baizean) was accepted by the NMPA. It is speculated that the new indication is the combination chemotherapy for patients with previously untreated advanced or metastatic esophageal squamous cell carcinoma (ESCC). This is the 11th indication of the product declared for marketing in China, nine indications of which had been approved for marketing in the past.

NMPA – Clinical Trials

[Approval]

2. On August 22, the CDE official website revealed that the clinical trial application for Ascletis’ASC10 was approved. ASC10 is a COVID-19 oral candidate drug polymerase (RdRp) inhibitor developed independently by Ascletis, with a new and differentiated chemical structure compared to its single prodrug, molnupiravir. On August 3, ASC10 was approved by the FDA for a Phase Ib clinical trial in patients with mild to moderate COVID-19.

3. On August 22, Shanghai Pharma announced that its B013 injection was approved by the NMPA for Phase II clinical trials. The indications are the first-line treatment of locally advanced or metastatic triple-negative breast cancer. B013 injection is a novel human recombinant monoclonal antibody product. Shanghai Pharma signed and entered into the license agreement with Oncternal and received the exclusive rights in Greater China in September 2018.

4. On August 23, the CDE revealed that the fourth-generation EGFR inhibitor of Qilu Pharmaceutical, QLH11811, was approved for clinical use. Its indication is the advanced NSCLC with EGFR and other driver gene abnormalities. QLH11811 shows better activity than the third-generation inhibitor, osimertinib, in the wild-type EGFR, the activating mutation ex19del, and the multiple combinatorial resistance mutations, and especially has the highest activity against the L858R/C797S combinational mutation (IC50=0.32nM). There have been nine EGFR inhibitors targeting the C797S mutation in the clinical stage worldwide.

5. On August 24, the anti-CD112R monoclonal antibody injection (project code: JS009) independently developed by Junshi Biosciences was approved by the CDE for clinical trials to treat advanced solid tumors. JS009 is a recombinant humanized IgG4 monoclonal antibody targeting CD112R. No product targeting CD112R has been approved for marketing in China or abroad by now.

6. On August 24, Keymed Biosciences Inc. and InnoCare Pharma announced that CM369, a monoclonal antibody targeting CCR8 developed by their joint venture, Tiannuo Jiancheng, was approved for clinical trials. Its indication is advanced solid tumors. There are 21 CCR8 monoclonal antibody products in development worldwide, of which six have entered the clinical development stage.

[Application]

7. On August 22, the CDE official website revealed that the clinical trial application of Akeso, Inc.’s AK129 injection was accepted for the treatment of cancers. AK129 is a bispecific antibody targeting human PD-1 and LAG3 developed by Akeso, Inc. Preclinical research has shown that AK129 has superior antigen binding properties to effectively block the PD-1/LAG-3 signaling pathway, and it can also promote the IL-2 and IFN-γ production in PBMC. Currently, the PD-1/LAG3 bispecific antibodies of EpimAb Biotherapeutics, Innovent, Zai Lab, and Roche have all entered the clinical stage in China.

8. On August 23, the clinical trial application of the MVA-BNRSV vaccine, jointly developed by BavarianNordic and Nuance, was accepted for the prevention of respiratory syncytial virus (RSV) infection. MVA-BNRSV has been granted the breakthrough therapy designation (BTD) by the FDA.

9. On August 24, the CDE announced that the clinical application of Roche Tiragolumab injection was accepted again. Eight clinical trials of Tiragolumab, a TIGIT monoclonal antibody, have been registered in China, including one Phase I, one Phase II, two Phase Ib/II, and four Phase III clinical trials. The proposed indications are NSCLC, extensive-stage small cell lung cancer, esophageal squamous cell carcinoma, gastric cancer, liver cancer, etc.

FDA - Marketing

[Application]

10. On August 22, Pfizer and BioNTech announced that they had applied to the FDA for emergency use authorization (EUA) of OmicronBA.4/BA.5-adapted bivalent COVID-19 mRNA vaccine for individuals 12 years of age and older. The bivalent vaccine contains mRNA encoding the original SARS-CoV-2 spike protein and mRNA encoding the spike protein of OmicronBA.4/BA.5 variants.

11. On August 22, MinervaNeurosciences announced that it had submitted a new drug application (NDA) for roluperidone to the FDA for the treatment of negative symptoms in patients with schizophrenia. Roluperidone is a 5-HT2A and σ2 receptor antagonist originally developed by Mitsubishi Tanabe.

EC - Marketing

[Approval]

12. On August 22, Gilead announced that the European Commission (EC) had approved lenacapavir (brand name: Sunlenca) injection and tablets for the treatment of multi-drug resistant HIV-1 infected patients who have received multiple prior treatments under combination with other antiretroviral drugs. Lenacapavir, a first-in-class long-acting HIV capsid inhibitor, is the only HIV therapeutic drug approved for marketing, which can be dosed twice per year.

13. On August 24, BioMarin announced that the European Commission (EC) approved the conditional marketing of Roctavian (Valoctocogeneroxaparvovec) gene therapy. It is for the treatment of adult patients with severe hemophilia A without coagulation factor VIII inhibitors and adeno-associated virus 5 (AAV5) antibodies in their bodies. Roctavian is the first approved gene therapy for the treatment of hemophilia A patients. In addition, the EU has maintained the orphan drug designation for the therapy and granted a 10-year market exclusivity.

14. On August 24, Johnson & Johnson announced that the European Commission (EC) has approved Teclistamab (brand name: TECVAYLI) as a monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM). They have received at least three prior therapies, including immunomodulators, proteasome inhibitors, and an anti-CD38 antibody, but the disease has continued to progress since their last treatment. This is the first BCMA/CD3 bispecific antibody approved for marketing worldwide.

R&D

Clinical trials launching

15. On August 24, the drug clinical trial registration and information publicity platform of CDE indicated that the clinical trials of AstraZeneca/Ionis AZD8233 injection had been initiated in China. AZD8233 (also known as ION449) is a GalNAc (N-acetylgalactosamine) ASO drug for targeted inhibition of  PCSK9 mRNA translation and protein synthesis in hepatocytes.

Clinical data release

16. On August 24, Apellis announced key results from two Phase III trials (DERBY and OAKS) of its targeted complement C3 therapy pegcetacoplan. The data indicated that pegcetacoplan did not provide any benefit in terms of visual function improvement in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) at the 24th month's treatment and did not meet its key secondary endpoint, but its effects increased over time.

17. On August 24, Novartis announced that it had decided to temporarily suspend the ongoing Phase IIb clinical study evaluating its experimental Huntington's disease (HD) drug branaplam, citing possible side effects. During the regular data review process, the independent Data Monitoring Committee (DMC) of the VIBRANT-HD research recommended the suspension of dosing due to early signs of side effects reported in treated subjects.

Business

18. On August 22, Hansoh Pharmaceutical Group announced that its wholly-owned subsidiary had entered into an exclusive licensing and co-development agreement with Global Health Drug Discovery Institute (GHDDI). Pursuant to the licensing agreement, Henson Pharmaceuticals will obtain exclusive worldwide rights to develop, manufacture and commercialize the anti-novel coronavirus new drug candidate GDI4405. The total amount of business is up to RMB1.692 billion. The candidate is an oral small molecule SARS-CoV-2 3CL protease inhibitor that exhibits high potent antiviral activity on SARS-CoV-2 Delta and Omicron variants.

19. On August 25, Novartis announced its intention to separate its generic drug and biosimilar division, Sandoz, into a newly listed independent operating company, with the process expected to be completed in the second half of the next year. Novartis indicated that the separation of Sandoz by way of a 100% spin-off is in the best interest of shareholders, creating the No.1 European generics company and a global leader in biosimilars.

Policy

20. On August 25, the EU’s final revision of its good manufacturing practice (GMP) Annex 1 for sterile drug was officially released. The new Annex contains 59 pages, which will take effect within 1 year from the date of publication, i.e., no later than 25 August 2023, except for section 8.123, which will take effect one year later on 25 August 2024.