Hengrui Pharmaceutical Carellizumab has added two new indications, and the total number of approved indications has reached 8

Source of this article: Entrepreneurial Circle Author: Yu Kun

Wen | Yu Kun

Recently, Hengrui Pharmaceutical received approval documents from the State Drug Administration, and two new indications of the company's self-developed PD-1 inhibitor carrelizumab were approved for marketing.

The new indications approved are: combined with paclitaxel and carboplatin for first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer, and combined paclitaxel and cisplatin for first-line treatment of patients with unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma. So far, carellizumab has been approved for 8 indications in the five major tumors of lung cancer, liver cancer, esophageal cancer, nasopharyngeal cancer and lymphoma, which is currently the domestic PD-1 product with the largest number of approved indications and the widest coverage of tumor species.

Consolidate the position in the field of immunotherapy for lung cancer and achieve full coverage of NSCLC squamous cell carcinoma and non-squamous cell carcinoma

In patients with non-small cell lung cancer (NSCLC), squamous NSCLC patients account for about 30% of patients, and only chemotherapy options were available in the past, and the overall survival was only about 10 months, and a better treatment regimen was urgently needed.

The approval of the first-line treatment indications for carellizumab squamous NSCLC is based on the excellent results of the multicenter, randomized controlled, double-blind, phase III clinical study, the CameL-sq study. A total of 389 untreated patients with stage III.B-IV squamous NSCLC lung cancer were randomly assigned to the carellizumab combined chemotherapy group (193 cases) and the placebo combination chemotherapy group (196 cases) in the study.

The results of the study showed that the median progression-free survival (mPFS) of patients in the carelizumab plus chemotherapy group was 8.5 months after evaluation by the independent review committee, compared with only 4.9 months in the placebo plus chemotherapy group, and the risk of disease progression or death decreased by 63% (HR=0.37, 95% CI 0.29 to 0.47, unilateral P<0.0001). The carellizumab plus chemotherapy group also brought significant improvements in overall survival (OS), with the median OS not reaching and 14.5 months (HR =0.55, 95% CI 0.40 to 0.75, unilateral P<0.0001, which was statistically different), and the risk of death decreased by 45%. In addition, the carellizumab plus chemotherapy group significantly improved the objective response rate of treatment (ORR, 64.8% vs 36.7%). In terms of safety, the incidence≥ of grade 3 treatment-related adverse events was comparable in both groups (73.6% vs 71.9%), and no unexpected adverse effects were observed.

In both the Camel-sq study in the squamous NSCLC field and the CameL study in the non-squamous NSCLC field, it can be observed that the combination chemotherapy of carellizumab on the main efficacy indicators ORR, PFS and OS shows a more enhanced immunotherapy mechanism of action. The evaluation of synergies between immunotherapy and chemotherapy also requires attention to the duration of response (DoR) of combination therapy, with a median DoR of 17.6 months in carrelizumab combined with chemotherapy in non-squamous NSCLC and a median DoR of 13.1 months in carrelizumab plus chemotherapy in squamous NSCLC.

The success of cameL-sq and CameL studies and the approval of related indications marks the completion of the full coverage of NSCLC squamous cell carcinoma and non-squamous cell carcinoma in the NSCLC field, further consolidating its position in the field of lung cancer immunotherapy.

Completing the second line of esophageal squamous cell carcinoma and making a new move to the first line of treatment will bring survival benefits to more patients

Esophageal cancer is one of the most frequent malignant tumors in China, and about half of the new cases and deaths in China will be accounted for in 2020. Not only that, 70% of esophageal cancer patients in China are diagnosed with intermediate and advanced stages, and the 5-year survival rate is less than 20%. Over the years, Chinese scholars have been stepping in the field of esophageal cancer with remarkable results.

The approval of the first-line treatment indications for carellizumab for esophageal squamous cell carcinoma is based on the results of the MULTIcenter, randomized double-blind, Phase III clinical study, THE ESCORT-1st study. The study, led by the team of Professor Xu Ruihua of the Center for Cancer Prevention and Control of Sun Yat-sen University, is the world's first phase III clinical study of PD-1 monoclonal antibody combined with paclitaxel and cisplatin in the first-line treatment of advanced esophageal squamous cell carcinoma, with a total of 596 participants, randomized according to 1:1, who were treated with carellizumab + paclitaxel + cisplatin or placebo + paclitaxel + cisplatin, respectively. Results showed that carrelizumab combined with chemotherapy significantly extended median OS (15.3 months vs 12.0 months) and median PFS (6.9 months vs 5.6 months), improved ORR (72.1% vs 62.1%) and median DoR (7.0 months vs 4.6 months) in patients with advanced esophageal cancer compared with the control group.

Based on excellent data, the ESCORT-1st study was honored in the 2021 ASCO Conference Oral Report, and was published online in full by the Journal of the American Medical Association (JAMA), one of the international authoritative journals and one of the four major medical journals, becoming the world's first and only clinical study of immunotherapy for esophageal cancer published in JAMA Magazine. The 2021 new edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Esophageal Cancer also lists carellizumab combined with paclitaxel and cisplatin chemotherapy as a first-line treatment plan recommendation (Grade II expert recommendation, Class 1A evidence), and the RESULTS of ESCORT-1st have been widely recognized by the academic community at home and abroad.

In 2019, the landmark blockbuster research in the field of immunotherapy for esophageal cancer- ESCORT research achieved breakthrough success, and carellizumab was approved as a second-line treatment indication for esophageal squamous cell carcinoma. The approval of the first-line treatment indications for esophageal squamous cell carbocinoma marks that carellizumab combined with paclitaxel and cisplatin chemotherapy have officially become the new standard program for the first-line treatment of advanced esophageal squamous cell carcinoma, and also means that carellizumab has completed a new step from back-line treatment to first-line treatment in the treatment of advanced esophageal squamous cell carcinoma, which will bring survival benefits to more patients in the front-line treatment of advanced esophageal cancer.

The expansion of the indications for carriizumab continues to break through, leading the number of approved indications and the coverage of tumor species

Since its listing in May 2019, the exploration of carellizumab in different tumor species has fully blossomed, and good news has been frequently reported. At present, carellizumab has been approved for 8 indications in the five major cancers of lung cancer, liver cancer, esophageal cancer, nasopharyngeal cancer and Hodgkin lymphoma, and continues to lead the domestic PD-1 monoclonal antibody in the number of approved indications and the coverage of tumor species.

As a domestic PD-1 monoclonal antibody, the success of carriolizumab is of more different significance to Chinese patients: its research data is derived from Chinese patients and is suitable for guiding Chinese clinical practice; many of its indications are included in the national medical insurance directory, continuously improving the accessibility and affordability of immunotherapy.

As an innovative national pharmaceutical enterprise, Hengrui Pharmaceutical has been taking "science and technology-based, creating a healthy life for mankind" as its mission for many years, practicing the development strategy of innovation and international two-wheel drive, committed to solving unmet clinical needs, and striving to develop more innovative drugs that domestic patients can "use and afford". In the future, Hengrui Pharmaceutical will not forget its original intention, strive to innovate, and strive to develop more new drugs and good drugs, so that more patients can effectively benefit.