The marketing declaration of Eli Lilly's hypoglycemic drug tirzepatide in China

Drug Review

NMPA – Marketing

[Application]

1. On September 6, the CDE official website revealed that the marketing application of Biohaven's Rimegepant had been accepted, and its indication is speculated as the acute migraine of adults. Rimegepant, an oral CGRP receptor antagonist, has been approved by the FDA for the treatment of acute migraine and episodic migraine in adults. In May 2022, Pfizer acquired Biohaven with approximately US$ 11.6 billion and obtained Rimegepant.

2. On September 7, the CDE official website revealed that the marketing application of Eli Lilly's Tirzepatide had been accepted for the improvement of the blood sugar control of adult type 2 diabetic patients. Tirzepatide, approved for marketing by the FDA in May 2022, is a weekly injected GIP and GLP-1 receptor agonist which integrates the effects of two incretin into a new molecule. It also possesses a significant effect on losing weight.

3. On September 8, the CDE official website revealed that the marketing application of Stone Pharma’s PD-L1 antibody, Sugemalimab injection had been accepted. It is intended to be used for the single-drug treatment of relapsed or refractory extranodal natural killer/T cell lymphoma (R/RENKTL). In October 2020, Sugemalimab was recognized by the FDA as a breakthrough therapy for this indication. No PD-1 or PD-L1 antibody has been approved for the treatment of R/RENKTL at present.

NMPA – Clinical Trials

[Approval]

4. On September 6, the CDE’s official website revealed that the clinical trial application of Novo Nordisk's semaglutide tablets had been approved as an auxiliary treatment for weight management in adult patients with a reduced calorie diet and increased physical activity as well as those with an initial body mass index (BMI) ≥28kg/m2 (obesity), or ≥24kg/m2 and <28kg/m2 (overweight) and at least one weight-related comorbidity. The Semaglutide tablet is a long-acting GLP-1 receptor agonist composed of semaglutide and absorption enhancer SNAC.

5. On September 7, Luye Pharma announced that BA1106, developed by its subsidiary Boan Biotech, was approved for clinical trials, being the first anti-CD25 monoclonal antibody for the treatment of solid tumors in the clinical stage in China. The main mechanism of BA1106 is to reduce Treg cells in the tumor microenvironment and increase the proportion of effector T cells via antibody-dependent cell-mediated cytotoxicity (ADCC).

6. On September 7, the CDE official website revealed that the clinical trial application of BioNova Pharmaceuticals’ BN301 had been approved. It is intended for the treatment of hematological malignant tumors that have progressed after previous systemic therapy or are not properly treated. BN301 is a potential "first-in-class" ADC targeting CD74. BioNova Pharmaceuticals reached a US$ 200 million cooperation to obtain the development and commercialization rights of the drug in Greater China.

7. On September 7, the CDE official website revealed that the clinical trial application of HXYT-001, the autologous cell injection of BriSTAR Immunotech, had been approved. It is intended for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). HXYT-001 cell injection is an innovative drug of cell therapy developed by BriSTAR Immunotech based on STAR-T technology jointly exploited with Tsinghua University. The main mechanism is the adoption of humanized antibodies targeting T cells CD19 and CD20 Synthetic TCR and Antigen Receptor (STAR) modified T cells.

8. On September 8, the CDE official website revealed that the clinical trial application of InnoCare Pharma’s ICP-248 tablets had been approved for the treatment of malignant hematologic tumors. Independently developed by InnoCare Pharma, ICP-248 is a BCL2 inhibitor, which is intended as a single drug or in combination with BTK inhibitors and other drugs to treat malignant hematologic tumors, such as non-Hodgkin's lymphoma and acute lymphoblastic leukemia.

9. On September 8, the CDE official website revealed that three clinical trial applications of the first-in-class JBPOS0101 capsules submitted by Jingxin Pharmaceutical had been approved for the treatment of adult focal epilepsy. JBPOS0101 is a new antiepileptic drug developed by Bio-Pharm of Korea. In August 2021, Jingxin Pharmaceutical obtained exclusive rights to the R&D commercialization of the drug in China (including the Chinese mainland, Hong Kong, S.A.R., China, and Macau, S.A.R., China).

[Application]

10. On September 6, the CDE’s official website revealed that MSD's clinical trial application of the MK-0616 capsule had been approved for the treatment of hypercholesterolemia. MK-0616 is an oral cyclic peptide PCSK9 inhibitor. There are three PCSK9 inhibitors on the market now, i.e. Novartis's inclisiran, Amgen's evolocumab, and Regeneron/Sanofi's alirocumab. In June 2022, the PCSK-9 inhibitor, tafolecimab injection of Innovent, was declared for marketing, being the first PCSK9 inhibitor made in China and declared for marketing.

11. On September 8, the CDE official website revealed that the clinical trial application of Chinagene Tech’s ZVS101e injection had been approved to treat the Bietti crystalline dystrophy (BCD) caused by CYP4V2 mutation. ZVS101e, a gene therapy drug in ophthalmology, has been granted the Orphan Drug Designation by the FDA. It restores the function of retinal cells by copying the normal CYP4V2 gene to the retinal cells of patients through the rAAV virus, supplementing the expression of the normal CYP4V2 gene in retinal cells.

[Breakthrough therapy]

12. On September 8, the CDE official website revealed that it had been proposed to include CMG901, jointly developed by Keymed Biosciences and Lepu Biopharma, in the breakthrough therapy varieties. The indication is Claudin18.2 positive advanced gastric cancer with failed or intolerant first-line or above treatment. CMG901, an ADC targeting Claudin18.2, has been granted the Orphan Drug Designation and fast track by the FDA and is the first Claudin18.2 ADC entering the clinical stage in the world. No Claudin18.2 ADC is currently available worldwide.

FDA - Marketing

[Approval]

13. On September 8, Amylyx Pharmaceuticals announced that the FDA's Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted 7-2 in favor of the fact that the available study data of the company's investigational drug, Albrioza, can support its marketing application for the treatment of amyotrophic lateral sclerosis. Albrioza is a proprietary fixed-dose oral compound formulation of sodium phenylbutyrate and taurursodiol.

[Breakthrough therapy]

14. On September 7, Pfizer announced that its GBS6 had been granted the breakthrough therapy by the FDA. It can prevent GBS infection in newborns through maternal immunization. GBS6 is an investigational maternal vaccine that provides protection by targeting six major GBS serotypes (covering 98% of cases). The qualification recognition of the FDA was informed by the interim analysis of Phase II study (NCT03765073) of GBS6, evaluating the safety and immunogenicity of GBS6 in healthy pregnant women aged 18 to 40 years.

[Orphan Drug Designation]

15. On September 6, Brise Pharma announced that BR007 has been granted the Orphan Drug Designation by the FDA for the treatment of progressive Camurati-Engelmann disease (CED). BR007 is a small molecule drug conjugate with bone targeting that specifically inhibits the TGF-β receptor in bone tissue cells. Progressive CED is a rare autosomal dominant bone disease caused by a mutation in the transforming growth factor TGF-β gene on chromosome 19q13.

R&D

Clinical trials launching

16. On September 5, the drug clinical trial registration and information publicity platform of CDE announced that Eli Lilly had registered an international multi-center (including China) Phase III clinical research to evaluate the safety and efficacy of Donanemab injection for the treatment of early symptomatic Alzheimer's disease. Donanemab is an anti-β amyloid protein antibody developed by Eli Lilly.

17. On September 7, the drug clinical trial registration and information publicity platform of CDE announced that Hengrui Medicine had initiated a Phase I clinical trial in China to evaluate the safety, tolerability, and pharmacokinetics of HRS-4642 injection in advanced solid tumor subjects with the KRAS G12D mutation. HRS-4642 is the first drug approved for clinical trials in China for advanced solid tumors with KRAS G12D mutation.

18. On September 8, Walvax announced that the first subject enrollment of Phase III clinical trial to compare the immunogenicity of the nine-valent HPV vaccine with Gardasil 9 launched by its subsidiary, Zerun Biotechnology had been initiated, marking the official entry of Phase III clinical research. This is a randomized, blind, positive-controlled trial with a target enrollment of 1,200 subjects.

Clinical data release

19. On September 5, Astellas Pharma Inc. announced positive key results from a Phase III MOONLIGHT3 study of fezolinetant for the treatment of female patients with menopausal vasomotor symptoms (VMS) on the Chinese mainland. Fezolinetant is an oral selective neurokinin 3 receptor (NK3) antagonist independently developed by Astellas Pharma Inc. The marketing application of fezolinetant has been submitted to the FDA and is in process, with a PDUFA date of February 22, 2023.

20. On September 5, Zelgen Biopharmaceuticals announced the subgroup analysis results from the Phase III ZGDD3 study of donafenib tosilate tablets for locally advanced metastatic radioiodine-refractory differentiated thyroid carcinoma. For patients with no history of TKI treatment, the mPFS of the donafenib and placebo group is respectively 18.3 and 7.4 months.While for patients with a history of TKI treatment, it is 11.0 and 3.7 months, respectively. Donafenib tablet is a small molecule antitumor drug in the oral multi-targeted and multi-kinase inhibitor class developed by Zelgen Biopharmaceuticals.

21. On September 5, Boehringer Ingelheim announced positive results from Phase III InPedILD  trial of nintedanib in children and adolescents with fibrosing interstitial lung disease (ILD), meeting the co-primary endpoint. Nintedanib is a multi-targeted tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR).

22. On September 8, Teva announced at MTIS2022 that two independent studies demonstrated the effectiveness of Fremanezumab for the treatment of patients with migraine combined with depression. The injection of Fremanezumab quarterly or monthly can reduce monthly migraine attacks by more than 50% compared to the placebo group. Fremanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks the binding of CGRP to its receptor.

23. On September 8, Bayer/Regeneron jointly announced that the primary endpoints were met at the 48th week in two global pivotal Phase III trials - PHOTON and PULSAR – investigating novel aflibercept 8 mg with 12- and 16-week dosing regimens in patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME). The success of these two pivotal studies means that aflibercept 8 mg formulation can extend the treatment interval from 2 months to 4 months.

24. On September 8, Amgen announced the results of two Phase III studies of Apremilast, demonstrating the effectiveness of the drug in pediatric patients with moderate to severe plaque psoriasis and adult patients with moderate to severe genital psoriasis. Apremilast is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor with the specificity for cyclic adenosine monophosphate (cAMP).

Business

25. On September 7, Good Therapeutics announced that it had entered into a merger agreement with Roche. Roche will have exclusive rights to the technology platform for the development of PD-1-regulated IL-2 therapeutics and PD-1-regulated IL-2 receptor agonist therapy in Good Therapeutics' R&D pipeline. PD-1-regulated IL-2 therapeutics consist of targeting the PD-1 antibody binding domain and IL-2, enabling specific targeting of IL-2 activity to PD-1 + T cells to stimulate T cell anti-tumor immune responses and minimize systemic toxicity.