Novartis' Breakthrough Radiopharmaceutical Pluvicto Submitted for Market Approval in China | Weekly Milestones of Domestic Innovative Drugs

1. Novatim: Injectable KY-0301

Mechanism of Action: Targeting EGFR/c-Met Bispecific Antibody

Indications: Solid Tumors

On November 12, Novatim's IND application for the injectable drug KY-0301 was accepted by the CDE. KY-0301 is a bispecific antibody targeting EGFR/c-Met, developed based on the company’s proprietary nano-bispecific ADC technology platform “TPEBEN.” The drug simultaneously targets MET and EGFR, two critical tumor-associated targets, effectively inhibiting the growth and spread of tumor cells. It is currently in the safety evaluation phase in both China and the U.S., with clinical trials expected to commence in early 2025. Compared to similar drugs, KY-0301 utilizes nanobodies with smaller molecular weights and incorporates optimized affinity design to enhance the drug’s safety and efficacy. Preclinical studies have demonstrated that KY-0301 exhibits excellent anti-tumor activity and favorable safety.

2. AstraZeneca: AZD0022

Mechanism of Action: KRAS G12D Inhibitor

Indications: Solid Tumors

On November 13, AstraZeneca's IND for AZD0022 was accepted by the CDE. AZD0022 is a KRAS G12D inhibitor. In November 2023, AstraZeneca entered into a global exclusive licensing agreement with Yosen Jianheng Biotech, obtaining the global exclusive rights for the research, development, and commercialization of UA022. It is speculated that AZD0022 might be UA022. Preclinical studies have shown that UA022 exhibits potent anti-cancer activity, favorable safety, and good oral bioavailability.

3. BeOne Medicines: BG-60366 Tablets

Mechanism of Action: EGFR Degrader

Indications: Tumor

On November 14, the IND for BeOne Medicines' BG-60366 tablets was accepted by the CDE. BG-60366 is a novel EGFR chimeric degradation activating compound (CDAC) that can broadly cover various EGFR mutations, disrupt EGFR scaffold function, and produce sustained signal inhibition. Preclinical studies have shown that this product has high effectiveness against both osimertinib-sensitive and resistant EGFR mutations without affecting wild-type EGFR, demonstrates good proteomic selectivity, and exhibits strong efficacy with once-daily oral administration.

4. Genecradle: GC310 Adeno-Associated Virus Injection

Mechanism of Action: ——

Indications: Hepatolenticular Degeneration

On November 14, the IND for Genecradle's GC310 adeno-associated virus injection was accepted by the CDE. GC310 is an AAV gene therapy developed by Genecradle that carries a truncated ATP7B gene expression cassette and is intended for the treatment of Wilson’s disease. Preclinical studies have shown that GC310 can effectively reduce transaminase levels in the serum of Wilson’s disease model mice, decrease copper ion levels in the blood and urine, and significantly alleviate symptoms of Wilson’s disease.

5. Haiwang Pharmaceuticals: NEP018 Tablets

Mechanism of Action: ——

Indications: Gastrointestinal Tumors

On November 14, the IND for NEP018 tablets developed by Haiwang Pharmaceutical was accepted by the CDE. NEP018 is an innovative drug for gastrointestinal tumors, with inhibitory effects on highly carcinogenic targets such as vEGFR, c-MET, and NTRK. In animal tumor models, NEP018 demonstrated significant inhibitory effects on gastrointestinal malignancies and exhibited an excellent therapeutic window, showing potential clinical therapeutic value.

6. Renfu Pharmaceutical: HWH340 Tablet

Mechanism of Action: PRAP Inhibitor

Indications: Tumor

On November 15, the IND for HWH340 tablets from Renfu Pharmaceutical was accepted by the CDE. HWH340 is a PRAP inhibitor that induces apoptosis by preventing DNA repair, making cancer cells with DNA damage unable to replicate. Compared to similar target drugs already on the market abroad and in Phase 3 clinical trials, HWH340 demonstrates significant advantages in water solubility, metabolism, tissue distribution, and bioavailability. With high target selectivity, significant anti-tumor efficacy, and a wide safety window, it is an excellent choice for monotherapy or combination therapy for malignant tumors with homologous recombination deficiencies.

1. Novartis: Lutetium [177Lu] Texiveptide Injection

Mechanism of Action: Targeted PSMA Peptide-Conjugated Radionuclide

Indications: Prostate Cancer

On November 13, Novartis' new drug application for Lutetium [177Lu] Texiveptide Injection was accepted by the CDE. Lutetium [177Lu] Texiveptide is the PSMA-targeted radioligand therapy Pluvicto (formerly known as 177Lu-PSMA-617), which was approved by the U.S. FDA in March 2022 for the treatment of prostate cancer patients. This drug combines a targeting compound (ligand) with a therapeutic radioisotope (radionuclide) for precision cancer treatment. Once in the bloodstream, Pluvicto binds to target cells, including prostate cancer cells expressing PSMA (a transmembrane protein). Upon binding, the emitted energy from the radioisotope damages the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death. The Phase 3 VISION study showed that participants receiving Pluvicto plus standard of care (SOC) had a 38% reduction in the risk of death and a significantly reduced risk of radiographic disease progression or death (rPFS) compared to SOC alone.

2. Novartis: Gallium [68Ga] Gozetotide Injection Preparation Kit

Mechanism of Action: ——

Indications: Prostate Cancer

On November 13, Novartis' new drug application for the gallium [68Ga] gozetotide injection preparation kit was accepted by the CDE. After being radiolabeled with 68Ga, the product becomes a radioactive diagnostic agent, assisting doctors in accurately identifying PSMA-positive lesions in adult prostate cancer patients through positron emission tomography (PET), playing a crucial role in the diagnosis of prostate cancer.

3. CANbridge: Velaglucerase Alfa for Injection

Mechanism of Action: Enzyme Replacement Therapy

Indications: Gaucher's Disease

On November 13, the new drug application for CANbridge's velaglucerase alfa injection was accepted by the CDE. Velaglucerase alfa (CAN103), administered intravenously, specifically replenishes the deficient glucocerebrosidase in the lysosomes of patients with Gaucher disease. It is China’s first enzyme replacement therapy (ERT) developed for Gaucher disease and is intended for the treatment of both adult and pediatric patients with Type I and Type III Gaucher disease. Data from pivotal clinical trials showed that CAN103 achieved its primary efficacy endpoint in both the 60U/kg dose group (P<0.0001) and the lower 30U/kg dose group (P<0.001), which was the mean percentage reduction in spleen volume from baseline after 9 months of treatment. Gaucher disease, one of the most common lysosomal storage disorders, is caused by a deficiency in glucocerebrosidase (acidic β-glucosidase). It includes perinatal lethal type, Type I (non-neuronopathic), Type II (acute neuronopathic), and Type III (chronic neuronopathic), with Type I and Type III patients often surviving into adulthood.