China Adds 10 New Breakthrough Therapies in September, Including 5 for Cancer from Roche, GSK, Hengrui and Others

▎WuXi AppTec Content Team Report

In September 2024, which has just concluded, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has...Ten New Drugs Included in Breakthrough Therapy Designation. Among them, five new drugs are under development for cancer treatment, and these investigational anticancer drugs includeOncolytic virus products, BCMA-targeted ADC, HER2-targeted small molecule inhibitors, EZH2 small molecule inhibitors, EGFR×HER3 bispecific antibody ADCEtc.

New drugs included in the "Breakthrough Therapy" list often targetDiseases that severely endanger life or significantly affect the quality of survival, and has demonstrated significant advantages in efficacy or safety in clinical trials.Inclusion in the "Breakthrough Therapy Designation" helps shorten the new drug development cycle, enabling patients to access higher-quality treatment options more quickly.

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CNBG-Virogin Biotech (Shanghai) Co., Ltd.: VG161

Mechanism of Action: Anti-tumor Immune-enhancing Oncolytic Virus

Indications: Advanced Hepatocellular Carcinoma

CNBG-Virogin BiotechVG161The injection has been included in the CDE's breakthrough therapy category, with the indication beingAdvanced Hepatocellular Carcinoma (HCC) That Has Failed Standard TreatmentAccording to the news release from CNBG-Virogin Biotech (Shanghai) Co., Ltd., VG161 is aA novel anti-tumor immune-enhanced oncolytic virus based on herpes simplex virus type 1 (HSV-1), carrying four exogenous immune-modulating genes: IL12, IL15/15Rα (IL15 and IL15 receptor α subunit), and a PD-L1 blocking peptide (PDL1B).。According toCNBG-Virogin Biotech (Shanghai) Co., Ltd.PR Newswire introduction,Clinical trial data shows that VG161 monotherapyPatients with hepatocellular carcinoma who have previously failed second-line treatment, including checkpoint inhibitorsSignificant clinical benefits were observed in China, with a notable extension in overall survival (OS) compared to the control group.

GSK: Belantamab Mafodotin for Injection

Mechanism of Action: BCMA-Targeted ADC

Indications: Multiple Myeloma

Belantamab mafodotin injection (brand name: Blenrep), submitted by GSK, has been included in the breakthrough therapy category by the CDE for use in combination with bortezomib and dexamethasone to treatAdult patients with multiple myeloma who have received at least one prior therapyBlenrep is an antibody-drug conjugate (ADC) targeting BCMA. The product previously received accelerated FDA approval in 2020 for the treatment of relapsed/refractory multiple myeloma patients who have received at least four prior therapies.（RRMM）Patient. According to GSK's press release at the time, this was the world's first approved therapy targeting BCMA.

In June this year, GSK announced Blenrep at the investor conference inSecond-line and above treatments for RRMM patientsPhase 3 Trials DREAMM-7 and DREAMM-8 Yield Impressive Results. Analysis Shows,The median progression-free survival (PFS) for patients receiving Blenrep combination therapy was 36.6 months, nearly two years longer than the 13.4 months for patients in the active control group, and the risk of disease progression or death for patients receiving Blenrep combination therapy was reduced by nearly 60%., achieving the primary endpoint of the trial.

Cigno Pharmaceuticals: XNW5004 Tablets

Mechanism of Action: A New Generation of EZH2 Small Molecule Inhibitors

Indications: Peripheral T-Cell Lymphoma

XNW5004 Tablets Submitted by SignaPharm Have Been Included in the CDE's Breakthrough Therapy Designation for the Treatment of Relapsed or Refractory Peripheral T-Cell Lymphoma.XNW5004 is a new generation of EZH2 small molecule inhibitor. As an epigenetic drug, it can regulate the expression of tumor suppressor genes to inhibit tumor growth.The product has demonstrated promising anti-tumor efficacy in indications such as hematological malignancies and prostate cancer, and is currently in Phase 2 clinical trials.

According to phase 1 clinical trial data presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting, XNW5004 demonstrated favorable anti-tumor efficacy across all dose groups and cancer types, with good safety and tolerability. Additionally, based on its mechanism of action, XNW5004 has the potential to enhance the efficacy of AR inhibitors, PARP inhibitors, and anti-PD-1 therapies.

Takeda: TAK-861 Tablets

Mechanism of Action: OX2R Agonist

Indications: Narcolepsy Type 1

Takeda's TAK-861 tablets have been included in the CDE’s Breakthrough Therapy designation for the indication of Narcolepsy Type 1 (NT1).TAK-861 is an orally active orexin receptor 2 (OX2R) agonist. Agonists that activate the orexin 2 receptor may serve as substitutes for endogenous orexins, activating signaling pathways that promote wakefulness.。In June this year, Takeda announced positive results from the Phase 2b clinical trial of TAK-861 in treating type 1 narcolepsy.The primary endpoint showed that, in the Maintenance of Wakefulness Test (MWT), all dose groups compared with the placebo groupIndicator of Delayed Sleep OnsetShowed statistically significant and clinically meaningful improvements.AndImprovement was sustained over 8 weeks.

Hengrui Medicine: SHR-1918 Injection

Mechanism of Action: ANGPTL3 Monoclonal Antibody

Indications: Homozygous Familial Hypercholesterolemia

Hengrui Medicine's SHR-1918 Injection Granted Breakthrough Therapy Designation by CDE for Homozygous Familial Hypercholesterolemia. SHR-1918 is a monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3) independently developed by Hengrui Medicine.It reduces LDL-C and triglyceride (TG) levels in the serum by inhibiting the activity of ANGPTL3.Studies have shown that the half-life of its product ranges from 29.4 to 53.5 days. The product is currently in Phase 2 clinical trials targeting patients with homozygous familial hypercholesterolemia.The product is administered via subcutaneous injection, once every 4 weeks.。

According to publicly available data from Hengrui Medicine, the Phase 1 study results showed that SHR-1918 demonstrated significant effects in reducing serum LDL-C and TG levels, with a dose-dependent response.LDL-C reduction exceeded 30% at dose levels of 300mg and above, lasting more than 64 days, with a maximum reduction of 49.1%; TG reduction exceeded 50%, lasting more than 85 days, with a maximum reduction of 82.8%.。

Zhikang Hongyi: SC0062 Capsule

Mechanism of Action: ETA Antagonist

Mechanism of Action: IgA Nephropathy with Proteinuria

SC0062 capsule, developed by Zhikang Hongyi, has been included in the breakthrough therapy category by the CDE for the treatment of IgA nephropathy with proteinuria. SC0062 isA novel molecular design targeting chronic kidney disease, a highly selective endothelin receptor A (ETA) antagonist, can improve renal blood flow, reduce proteinuria, and alleviate inflammation and fibrosis processes.In July this year, Zhikang Hongyi announced that SC0062 had reached the primary endpoint of reducing proteinuria in the Phase 2 clinical trial 2-SUCCEED for chronic kidney disease (CKD). The product also demonstrated clear dose-dependency and good safety.

Roche: ZN-A-1041 Enteric-Coated Capsules

Mechanism of Action: HER2-Targeted Small Molecule Inhibitor

Indications: HER2-positive advanced breast cancer with brain metastases

ZN-A-1041 Enteric-Coated Capsules Submitted by Zanrong Pharmaceutical Included in CDE’s Breakthrough Therapy Designation, Combined with Capecitabine and Trastuzumab for Patients Progressed After Prior Trastuzumab-Containing TreatmentHER2-positive advanced breast cancer patients with brain metastasesZN-A-1041 is an orally administered small-molecule HER2-targeted inhibitor.Highly Permeable to the Blood-Brain Barrier. Roche previously reached an agreement with Zanrong Pharmaceutical toTotal approximately USD 680 millionAcquire the global rights to this investigational drug.

The 2023 American Society of Clinical Oncology (ASCO) Annual Meeting disclosed preclinical and early clinical data of ZN-1041. The study results showed that, in 19 HER2+ breast cancer patients with brain metastases (BCBM) who had at least two tumor assessments,ZN-1041 in Combination with Capecitabine and TrastuzumabObjective Response Rate (ORR)78.9%,Intracranial ORR (iORR)At 73.7%, the disease control rate (DCR) was 100%.。

Haisco: HSK31858 Tablets

Mechanism of Action: DPP1 Inhibitor

Indications: Non-cystic fibrosis bronchiectasis

HSK31858 Tablets Submitted by Haisco Have Been Included in the CDE’s Breakthrough Therapy Designation, with the Proposed Indication for Non-Cystic Fibrosis Bronchiectasis.HSK31858 tablets are an orally administered, potent, and highly selective DPP1 inhibitor independently developed by Haisco. Its mechanism of action involves inhibiting DPP1, thereby suppressing downstream neutrophil serine proteases (NSPs) associated with bronchodilation inflammation to exert its pharmacological effects.In May 2024, Haisco announced that the Phase 2 clinical study of HSK31858 tablets in patients with non-cystic fibrosis bronchiectasis has been completed, and the study met its pre-specified endpoints.

I-Mab: Plonarib Injection

Mechanism of Action: GM-CSF Neutralizing Antibody

Indications: Hemophagocytic Lymphohistiocytosis Associated with Rheumatic Diseases

I-Mab's New Drug Plonarib Injection Granted Breakthrough Therapy Designation by CDE for the Indication ofRecurrent/Refractory Macrophage Activation Syndrome Associated with Rheumatic Diseases (R/R MAS)Punarilizumab is a neutralizing antibody against human granulocyte-macrophage colony-stimulating factor (GM-CSF), which can effectively inhibit macrophage-, neutrophil-, and dendritic cell-mediated inflammatory responses, thereby reducing tissue inflammation and damage.

According to the press release from I-Mab Biopharma, the Breakthrough Therapy Designation was based on the positive clinical results obtained from the Phase 2 clinical study of Plonmarlimab in treating MAS patients. Among 12 evaluable patients with MAS who did not respond well to a 3-day high-dose steroid pulse therapy,All patients achieved clinical response after 8 weeks of treatment with Plonarlimab; the steroid dosage for all patients was reduced by at least 50%.In addition, the treatment was well tolerated, with most adverse events being grade 1, and no dose-limiting toxicity was observed.

Baili Pharmaceutical: Injectable BL-B01D1

Mechanism of Action: EGFR×HER3 Bispecific Antibody ADC

Indications:Non-Small Cell Lung Cancer

Baili Pharmaceutical's research and developmentEGFR×HER3 Bispecific ADC ProductTwo indications for the injectable BL-B01D1 have been included in the breakthrough therapy category by the CDE, namely: locally advanced or metastatic cases that have previously failed treatment with anti-PD-1/PD-L1 monoclonal antibodies and platinum-based chemotherapy.EGFRWild-type Non-Small Cell Lung CancerPatients who have failed EGFR-TKI treatmentEGFRLocally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer with Sensitizing MutationsPatient.

In July this year, The Lancet Oncology (The Lancet Oncology）Announced the use of BL-B01D1 forPatients with locally advanced or metastatic solid tumorsResults of the first-in-human phase 1 study.A total of 144 patients were enrolled across all Q3W dose levels, including89 patients with NSCLC. The study results showed that BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced solid tumors.Especially inEGFRIn m NSCLC patients, the ORR was 61.8% and the DCR was 91.2%.. And inEGFRIn wt NSCLC patients, the ORR was 40.5%.DCR is 95.2%。

In addition,BL-B01D1TargetingPreviously treated with PD-1/PD-L1 monoclonal antibody combined with platinum-based chemotherapy for recurrent or metastatic diseaseEsophageal Squamous Cell CarcinomaThe indication has also been proposed for inclusion in the breakthrough therapy category and is currently under public notice. The 2024 ESMO Congress, which just concluded, released efficacy and safety data for BL-B01D1 in esophageal squamous cell carcinoma. The ORR was 33.8% (with confirmed cases at 29.7%), the DCR was 70.3%, the mPFS was 4.1 months, and the mOS was 6.6 months.

In addition to the aforementioned products, VibeBioAnti-PD-L1/4-1BB bispecific antibodyLBL-024 for InjectionFor the indication of advanced extrapulmonary neuroendocrine carcinoma, Jacobio's KRAS inhibitorJAB-21822 TabletsForKRAS G12CMutation-Positive Colorectal Cancer Indication, Hengrui Medicine Improved New DrugHR19042 CapsuleFor the indication of active autoimmune hepatitis, a new generation EGFR-TKI drug developed by Dizhe PharmaceuticalsDZD9008 TabletsThe indication for non-small cell lung cancer has also been proposed by the CDE to be included in the breakthrough therapy category and is currently under public announcement.

We look forward to the smooth progress of subsequent clinical studies of these investigational new drugs, which will bring new treatment options to more patients as soon as possible.

[2] Official websites of various companies and public materials