China clears homegrown PD-1 inhibitors for solid tumors in March
Danni Yin ·04/25/2022
China NMPA Approval Tracker


The month of March saw a string of approvals handed out by the NMPA, with the most significant being two domestically developed anti-PD-1 inhibitors getting green lighted to treat MSI-H/dMMR solid tumors in China for the first time ever.


Shanghai biotech firm Henlius celebrated the first approval of its internally-developed  Hansizhuang (serplulimab) for the treatment of adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) solid tumors that have failed to respond to previous standard treatments.


Separately, biotech giant BeiGene saw its Baize'an (tislelizumab) cleared for its seventh indication – advanced unresectable or metastatic MSI-H or mismatch repair deficient (dMMR) solid tumors. The drug can be used to treat adult patients with advanced colorectal cancer who had been treated with fluoropyrimidine, oxaliplatin and irinotecan, as well as those with other advanced solid tumors who develop disease progression after prior treatment and have no satisfactory alternative treatment options.


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Previously, Merck Sharp & Dohme's Keytruda and Suzhou-based Alphamab’s subcutaneous PD-L1 envafolimab were the only monoclonal antibodies approved for MSI-H/dMMR solid tumors in China.


For this pan-cancer indication, patients are screened for specific MSI-H tumor markers, rather than classifying the tumor types. They include endometrial, colorectal, gastric and ovarian cancer, as well as renal cell carcinoma.


Competition is fierce in this particular space in China, as there are more than 10 active clinical trials for MSI-H/dMMR solid tumors. Most are sponsored by domestic players who are testing their monoclonal antibodies that target PD-1, PD-L1 and CTLA-4, as well as bispecific antibodies.


Tapping new indications


In China, most of the approved PD-1/L1 antibodies have covered high incidence tumors, such as non-small cell lung cancer (NSCLC), hepatocellular carcinoma, gastric cancer, esophageal cancer and nasopharyngeal cancer.


To tap unexplored areas, new competitors have begun to seek indication differentiation and explore combination potential for their PD-1/L1 candidates.


Henlius adopts the Combo+Global development strategy for serplulimab, focusing on indication differentiation with MSI-H/dMMR solid tumors and extensive stage small cell lung cancer (ES-SCLC).


In December 2021, the Shanghai biotech firm announced that serplulimab and chemotherapy combination therapy met primary endpoint in overall survival (OS) in previously untreated ES-SCLC.


Junshi’s toripalimab, Innovent’s sintilimab and BeiGene’s tislelizumab have also moved on to phase III clinical trials for SCLC.


Cervical cancer is another area that sees several competitors.


China has yet to approval any immunotherapies for this indication, while the U.S. already approved pembrolizumab and tisotumab vedotin for recurrent/metastatic cervical cancer in 2021.


In March 2022, Gloria Pharma filed the second NDA for GLS-010 (zimberelimab) – the sixth homegrown PD-1 antibody in China – for the treatment of cervical cancer. The drug received breakthrough therapy designation from the NMPA in March 2021.


Qilu Pharma’s QL1604, Henlius’ serplulimab, Hengrui’s camrelizumab and Akeso’s PD-1/CTLA-4 bispecific antibody AK104 are also in phase III clinical trials for cervical cancer.


More approvals for NSCLC


The month of March also saw four drugs approved for the treatment of NSCLC. Among them are two ALK inhibitors, Takeda’s Alunbrig (brigatinib) and Betta Pharma’s Ensacove (ensartinib).


Takeda said the approval of Alunbrig marked its foray in the lung cancer space in China.


Meanwhile, Betta Pharma’s ensartinib was finally approved as the first-line therapy for non-small cell lung cancer, after it was cleared as the second-line therapy for ALK-positive NSCLC two years ago.


Chinese regulators also got their act together to issue speedier clearances for foreign drugs in additional indications.


They granted clearance to Roche’s Tecentriq (atezolizumab) as adjuvant therapy for NSCLC five months after their U.S. counterparts. Tecentriq is the frontrunner in the PD-L1 clinical development race in China. It is also the first immunotherapy approved for the treatment of NSCLC as adjuvant therapy in China.


Novartis’ Tafinlar (dabrafenib) plus Mekinist (trametinib), targeting BRAF and MEK1/2 separately, also got the green light to be used in combination to treat metastatic NSCLC that has a certain type of abnormal “BRAF V600E” gene.


In addition, the NMPA accepted Merck KGaA's marketing application for c-Met inhibitor Tepmetko (tepotinib) for the treatment of metastatic NSCLC harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.


Other competitors in China include HUTCHMED’s Orpathys (savolitinib) and Novartis’ Abrecta (capmatinib). Orpathys remains the only approved c-Met inhibitor since April 2021.


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Keywords: PD-1 inhibitors March NMPA MSI-H/dMMR solid tumors
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