Bristol Myers Squibb and Exelixis Receive Positive CHMP Opinion for Opdivo (nivolumab) Plus Cabometyx (cabozantinib) as First-Line Treatment for Advanced Renal Cell Carcinoma in the EU

Mar 09, 2021 20:03 CST Updated 20:03

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European Medicines Agency

The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

March 09, 2021 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval of the anti-PD-1 therapy Opdivo (generic name: nivolumab) in combination with the targeted anticancer drug Cabometyx (cabozantinib) as first-line treatment for adult patients with advanced renal cell carcinoma (RCC).Now, the CHMP’s opinion will be submitted to the European Commission (EC) for review, which is expected to make a final review decision within the next two months. Data from the pivotal Phase 3 CheckMate-9ER trial show that, compared with the first-line standard-of-care drug Sutent (generic name: sunitinib, a tyrosine kinase inhibitor,PfizerCompared with the development), the “immunotherapy + targeted therapy” regimen comprising Opdivo and Cabometyx demonstrated sustained therapeutic benefits and significantly improved quality of life.

In terms of U.S. regulatory oversight,FDAApproved in January 2021, the Opdivo + Cabometyx regimen is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). The Opdivo and Cabometyx “immunotherapy + targeted therapy” combination was granted priority review and real-timeTumorThe pilot program for review (RTOR) has been approved, and it is authorized for all risk classifications of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). This approval will provide an important new first-line treatment option for patients with advanced or metastatic renal cell carcinoma (RCC) who have not previously received treatment. This approval expands Bristol-Myers Squibb’s position in the first-line treatment of advanced RCC. Previously, the dual immunotherapy of Opdivo and Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) had been approved as a standard therapy for intermediate- or high-risk patients with advanced RCC in the first-line setting.

Dana Walker, Vice President and Head of Genitourinary Cancer Development at Bristol-Myers Squibb (BMS), stated: “In recent years, we have witnessed transformations and significant advancements in the treatment landscape for renal cell carcinoma (RCC), which have helped improve patient outcomes. Following regulatory approval of Opdivo plus Yervoy, BMS launched this dual immunotherapy regimen for RCC patients in the European Union for the first time, demonstrating durable, long-term survival benefits in the pivotal CheckMate -214 trial. Now, with the positive recommendation from the Committee for Medicinal Products for Human Use (CHMP), we are one step closer to launching another Opdivo-based regimen, which has demonstrated superior efficacy in patients who may benefit from the combination of immunotherapy and tyrosine kinase inhibitors.”

Renal Cell Carcinoma (Image source: vecteezy.com)

United StatesFDAThe approval and the positive review opinion from the EU CHMP are both based on the results of the pivotal Phase III CheckMate-9ER trial. The data showed that in patients with previously untreated advanced RCC, the "immunotherapy + targeted therapy" regimen Opdivo + Cabometyx demonstrated significant improvements across all efficacy endpoints compared to the first-line standard-of-care drug Sutent (generic name: sunitinib, a tyrosine kinase inhibitor developed by Pfizer), including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

Specific data are as follows: (1) For overall survival (OS), the Opdivo + Cabometyx group showed a significant 40% reduction in the risk of death compared with the Sutent group (HR=0.60; 98.89% CI: 0.40–0.89; p=0.0010), with median OS not reached in either group. (2) For the primary endpoint, progression-free survival (PFS), the Opdivo + Cabometyx group demonstrated a doubling of PFS compared with the Sutent group (median PFS: 16.6 months vs. 8.3 months; HR=0.51; 95% CI: 0.41–0.64; p<0.0001). (3) For objective response rate (ORR), the Opdivo + Cabometyx group achieved twice the rate of the Sutent group (56% vs. 27%), along with a higher complete response (CR) rate (8% vs. 5%). (4) For duration of response (DOR), the Opdivo + Cabometyx group had a longer DOR than the Sutent group (median DOR: 20.2 months vs. 11.5 months). Notably, all these key efficacy results were consistent across prespecified subgroups based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk categories and PD-L1 status.

In the study, the combination of Opdivo and Cabometyx was well tolerated, reflecting the known safety profile of immunotherapy and tyrosine kinase inhibitors (TKIs) in the first-line treatment of advanced renal cell carcinoma (RCC). Based on the National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy (NCCN-FACT) Kidney Symptom Index 19 (FKSI-19) scores, patients treated with Opdivo plus Cabometyx demonstrated significantly better health-related quality of life than those treated with Sutent at most time points.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing more than 140,000 deaths worldwide each year. The incidence of RCC in men is approximately twice that in women, with the highest rates observed in North America and Europe. Globally,DiagnosisFor patients with metastatic or advanced renal cell carcinoma, the 5-year survival rate is only 12.1%. In recent years, despite some therapeutic advances, additional treatment options are still needed to prolong survival.

The results of the CheckMate-9ER study clearly demonstrate that the first-line treatment of patients with advanced or metastatic renal cell carcinoma (RCC) with the Opdivo and Cabometyx “immunotherapy + targeted therapy” combination regimen yields clinically meaningful improvements in key efficacy endpoints, including progression-free survival (PFS) and overall survival (OS). Furthermore, the combination of Opdivo and Cabometyx exhibits a favorable safety profile.

The active pharmaceutical ingredient of Cabometyx is cabozantinib, a tyrosine kinase inhibitor (TKI) that exerts its antitumor effects by selectively inhibiting the MET, VEGFR2, and RET signaling pathways, thereby killingTumorcells, reducing metastasis and inhibiting angiogenesis. In the United States, the European Union, Japan, and other countries and regions worldwide, Cabometyx has been approved for the treatment of patients with advanced renal cell carcinoma (RCC), as well as patients with hepatocellular carcinoma (HCC) who have previously received sorafenib treatment.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to uniquely harness the body’sAutoimmunitySystem helps restore resistanceTumorImmune Response. Opdivo was first approved in Japan in July 2014, becoming the world’s first approved PD-1 immunotherapy. Currently, Opdivo has become an important treatment option for various types of cancer.

For the treatment of renal cell carcinoma (RCC), the approved indications for Opdivo are: (1) for patients with advanced RCC who have previously received anti-angiogenic therapy; (2) in combination with Yervoy (ipilimumab, an anti-CTLA-4 monoclonal antibody) as first-line treatment for patients with intermediate- or high-risk advanced RCC. (Bioon.com)

Original Source: Bristol Myers Squibb Receives Positive CHMP Opinion for Opdivo® (nivolumab) in Combination with Cabometyx® (cabozantinib) as First-Line Treatment for Patients with Advanced Renal Cell Carcinoma