Since the implementation of China's National Medical Products Administration (NMPA) "Breakthrough Therapy Drug Work Procedures" in 2019, many investigational new drugs have been added to the list of "breakthrough" drugs each year, continuously providing patients with various serious diseases better treatment options in terms of efficacy or safety. Based on the public information of breakthrough therapy varieties from the NMPA Center for Drug Evaluation (CDE) and the NDA submission/priority review records of these drugs, this article will summarize 12 "breakthrough" new drugs that are expected to be approved for marketing in China within the next five months (the second half of 2024), and explore which disease patients these potential breakthrough therapies could benefit. (This article is an incomplete statistic, only summarizing new drugs expected to gain first-time approval, excluding new indications.)

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Legend Biotech: Cilta-cel (LCAR-B38M CAR-T Cell Autologous Infusion Preparation)

Mechanism of Action: BCMA-Targeted CAR-T Cell Therapy

Indications: Relapsed or Refractory Multiple Myeloma

Cilta-cel is a BCMA-targeted CAR-T therapy jointly developed by Johnson & Johnson and Legend Biotech. In August 2020, the product was designated as a breakthrough therapy by the CDE for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least three prior lines of therapy, including at least one proteasome inhibitor and at least one immunomodulatory agent. In January 2023, the product's marketing application in China for the treatment of relapsed or refractory multiple myeloma was granted priority review. This product has already been approved for marketing by the U.S. FDA.

According to data disclosed by Legend Biotech in April 2023, the first Phase 3 results of the CARTITUDE-4 study on Cilta-cel showed that it reduced the risk of disease progression/death by 74%. In the LEGEND-2 study conducted in China with ≥5 years of follow-up, the median overall survival was 55.8 months, and 18% of R/R MM patients were symptom-free, increasing the possibility of a cure for patients who have undergone multiple prior treatments.

Hengrui Medicine: Icatibant Tablets (SHR0302)

Mechanism of Action: JAK1 Inhibitor

Indications: Autoimmune diseases (Atopic Dermatitis)

Ivarmacitinib Tablet is an orally administered, highly selective JAK1 inhibitor. Studies have shown that JAK1 inhibitors control the condition by modulating various cytokines associated with the pathology of atopic dermatitis. Based on positive results from a Phase 2 study in the atopic dermatitis population, the product was designated as a breakthrough therapy by the CDE. In June 2023, Ivarmacitinib Tablet submitted its first marketing application in China for the treatment of atopic dermatitis, followed by two additional submissions for new indications: the treatment of adolescent atopic dermatitis and rheumatoid arthritis.

In March 2024, the Phase 3 study results of Emactuzumab for the treatment of moderate to severe atopic dermatitis were disclosed: After 16 weeks of treatment with Emactuzumab, patients with moderate to severe AD showed significant improvement in skin lesions and itching symptoms. A 52-week long-term follow-up confirmed that the drug's efficacy was sustained over the long term, with overall good safety. In January 2018, Hengrui Medicine licensed the exclusive rights of Emactuzumab in the United States, the European Union, and Japan to Arcutis Company for a total amount of up to $223 million.

Johnson & Johnson: JNJ-61186372 Injection (amivantamab, Rybrevant Injection)

Mechanism of Action: Bispecific Antibody Targeting EGFR and MET

Indications: Non-Small Cell Lung Cancer

Amivantamab, developed by Johnson & Johnson, is a bispecific antibody targeting EGFR and MET. It not only blocks the binding of ligands to EGFR and MET and promotes receptor degradation but also triggers antibody-dependent cellular cytotoxicity. In September 2020, amivantamab was designated as a breakthrough therapy by the CDE for treating metastatic or surgically unresectable non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations who progressed during or after platinum-based doublet chemotherapy or were intolerant to platinum-based chemotherapy. Since 2023, multiple marketing applications for the injection of amivantamab have been submitted in China. Clinical studies of amivantamab for treating locally advanced or metastatic EGFR-mutated NSCLC have yielded positive results.

Innovent Biologics/Great Health Pharmaceuticals: Fuzelase Tablets

Mechanism of Action: KRAS G12C Inhibitor

Indications: Non-small cell lung cancer, Colorectal cancer

Fuzelase Tablets (IBI351, GFH925 Tablets) are a highly efficient oral new molecular entity compound. Innovent Biologics has reached an exclusive global licensing agreement with GenFleet Therapeutics, obtaining exclusive rights to develop and commercialize the product in China as the exclusive partner. Previously, Fuzelase Tablets were included twice by the CDE as a breakthrough therapy designation, for the treatment of patients with advanced non-small cell lung cancer harboring KRAS G12C mutations and patients with advanced colorectal cancer harboring KRAS G12C mutations.

In October 2023, the marketing application for Fuzelase tablets was accepted by the CDE and included in the priority review, intended for the treatment of advanced non-small cell lung cancer with KRAS G12C mutations. Public information indicates that this is also the first KRAS G12C inhibitor to submit a marketing application in China. According to the latest research data released by GenFleet Therapeutics in June this year, phase 2 clinical study data on Fuzelase tablets combined with cetuximab as first-line treatment for non-small cell lung cancer were selected for an oral presentation at ASCO and featured in the breakthrough research abstract. The results showed an objective response rate (ORR) of 81.8% and a disease control rate (DCR) of 100%; the majority of evaluable patients (27/33) achieved tumor relief, including one case of complete response, and two cases of partial response where a 100% reduction in target lesions was observed.

Lilly: Donanemab Injection

Mechanism of Action: β-Amyloid Antibody

Indications: Early Alzheimer's Disease

Donanemab Injection is a monoclonal antibody developed by Eli Lilly and Company that binds to the N3pG subtype of beta-amyloid protein. It was approved by the FDA in July this year for the treatment of adults with early symptoms of Alzheimer's disease (AD). In China, Donanemab was included in the breakthrough therapy designation by the CDE in January 2023 for the treatment of early symptomatic Alzheimer's disease, including mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease.

In November 2023, the product's new drug application was granted priority review by the CDE for the proposed treatment of early Alzheimer's disease. According to clinical data disclosed by Eli Lilly, pivotal Phase 3 studies showed that donanemab slowed cognitive and functional decline by up to 35% compared to placebo, and reduced the risk of disease progression by up to 39% over 18 months; compared to the start of the study, monthly 30-minute infusions reduced amyloid plaques by an average of 84%.

Kelun BioTech: Lukansatuzumab

Mechanism of Action: TROP2-Targeted ADC

Indications: Triple-negative breast cancer, etc.

Lukang Satuzumab (SKB264 for Injection) is an ADC targeting TROP2 developed by Kelun-Biotech. The product has been included in the breakthrough therapy category by the CDE four times, respectively for: locally advanced or metastatic triple-negative breast cancer (TNBC), locally advanced or metastatic EGFR-mutated non-small cell lung cancer, locally advanced or metastatic HR-positive/HER2-negative breast cancer, and PD-L1-negative triple-negative breast cancer. In November 2023, the drug's marketing application was granted priority review by the CDE for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have previously received at least two systemic treatments (at least one of which was for advanced or metastatic stages).

ConnieMab: CM310 Recombinant Humanized Monoclonal Antibody Injection (Spesolimab)

Mechanism of Action: IL-4Rα Targeting Monoclonal Antibody

Indications: Atopic Dermatitis

Sipulimab is a highly effective, humanized monoclonal antibody targeting the interleukin-4 receptor alpha subunit (IL-4Rα). In June 2022, the product's research for treating moderate to severe atopic dermatitis was included by the CDE as a breakthrough therapy. In November 2023, its marketing application was granted priority review for treating adult patients with moderate to severe atopic dermatitis who have inadequate response to topical medications or are unsuitable for such treatments. Additionally, marketing applications for its indications in seasonal allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP) have also been submitted.

Tainuomab: TNM002 Injection

Mechanism of Action: Recombinant Natural Full Human Monoclonal Antibody Against Tetanus Toxin

Indications: Prevention of tetanus

TNM002 Injection is a recombinant anti-tetanus toxin fully human monoclonal antibody drug developed by Tanox Pharma. In February 2022, the product was announced by the CDE to be included in the breakthrough therapy designation for tetanus prevention. In November 2023, the marketing application of TNM002 was granted priority review by the CDE for emergency tetanus prevention in adults. Existing clinical data shows that after administration, anti-tetanus antibodies in the body quickly reach a high level of tetanus protection and maintain a prolonged protective duration.

Innovent Biologics/CTTQ: Geshuruixi Tablets

Mechanism of Action: KRAS G12C Selective Inhibitor

Indications: Non-small cell lung cancer, Colorectal cancer, Pancreatic cancer

Garsorasib (garsorasib, D-1553 tablets) is a novel and highly effective KRAS G12C selective inhibitor developed by Innovent Biologics. Innovent Biologics has reached a collaboration with Zhengda Tianqing, granting the latter exclusive rights to develop, register, manufacture, and commercialize the product in mainland China during the agreement period. The product has been included three times by the CDE as a breakthrough therapy for the following: KRAS G12C mutant non-small cell lung cancer, KRAS G12C colorectal cancer, and KRAS G12C mutant pancreatic ductal adenocarcinoma.

In December 2023, the listing application for Gezuruxi was included in the priority review by the CDE, applicable for the treatment of locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations. Early clinical results of Gezuruxi in treating non-small cell lung cancer with KRAS G12C mutations showed an objective response rate (ORR) of 40.5%, a disease control rate (DCR) of 91.9%, and a median progression-free survival (mPFS) of 8.2 months.

BeiGene: Zenidatamab Injection

Mechanism of Action: HER2 Bispecific Antibody

Indications: HER2-highly expressed unresectable locally advanced or metastatic biliary tract cancer

Zanidatamab (ZW25) is a HER2-targeted bispecific antibody that can simultaneously bind to two non-overlapping HER2 epitopes. This drug originated from a licensing collaboration worth up to approximately $430 million between BeiGene and Zymeworks in 2018, with BeiGene holding exclusive rights in Asia (excluding Japan), Australia, and New Zealand. In February 2022, the product was included in the breakthrough therapy designation by the CDE for monotherapy treatment of HER2-positive locally advanced unresectable or metastatic biliary tract cancer (BTC) after failure of prior systemic chemotherapy.

In November 2023, the marketing application for Zenidatamab for the treatment of patients with HER2-overexpressing biliary tract cancer was granted priority review by the CDE. In a global Phase 2b study targeting this indication, the confirmed objective response rate (cORR) was 41%, with a median duration of response (DOR) of 12.9 months; among 33 responders, 49% had sustained responses, and 82% had a DOR ≥16 weeks.

Innovent Biologics/Bao Yuan Pharmaceuticals: Taletrectinib Capsules

Mechanism of Action: A New Generation of ROS1 Tyrosine Kinase Inhibitor (TKI)

Indications: Non-Small Cell Lung Cancer

Taletrectinib (AB-106) is a new-generation oral selective ROS1 inhibitor. Innovent Biologics and AnHeart Therapeutics (which has been acquired by Nuvation Bio) are jointly responsible for the development and commercialization of this product in Greater China. Two indications for this product have previously been granted breakthrough therapy designation by the CDE, for: non-small cell lung cancer patients with ROS1 fusion genes who have failed ROS1-TKI treatment, and non-small cell lung cancer patients with ROS1 fusion genes who have not received ROS1-TKI treatment.

Currently, the marketing applications of Taletrectinib for these two indications have been included in the priority review by the CDE. According to previously published news reports, in the Phase 2 TRUST-I clinical study, the objective response rates (ORR) for TKI-naive patients and ROS1-positive NSCLC patients who failed crizotinib treatment were 91% and 52%, respectively. Additionally, Taletrectinib continues to demonstrate robust anti-tumor activity in patients with measurable brain metastases and those with acquired resistance mutations (including G2032R).

Hengrui Medicine: Famitinib

Mechanism of Action: Multi-target Tyrosine Kinase Inhibitor

Indications: Cervical cancer, Non-small cell lung cancer

Famitinib Malate Capsules, a small-molecule multi-target tyrosine kinase inhibitor independently developed by Hengrui Medicine, exhibit inhibitory activity against various receptor tyrosine kinases and belong to the category of multi-target anti-angiogenic targeted drugs. The drug has been included in the breakthrough therapy designation by the CDE twice, for the indications of combination with Camrelizumab in treating recurrent or metastatic cervical cancer that has failed first-line or higher treatment, and as a first-line treatment for recurrent or metastatic non-small cell lung cancer with PD-L1 expression (TPS≥1%) without EGFR/ALK gene abnormalities.

In December 2023, the new drug application for Camrelizumab in combination with Famitinib capsules for the treatment of patients with recurrent or metastatic cervical cancer who failed prior platinum-based chemotherapy was accepted by the CDE. In the pivotal Phase 2 clinical study, compared to Camrelizumab monotherapy, this combination therapy significantly improved the objective response rate (ORR), which reached 41%, with rapid onset and long duration of response.

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