Bristol Myers Squibb Receives Positive CHMP Opinion for Opdivo Plus Yervoy as First-Line Treatment for Unresectable Malignant Pleural Mesothelioma

Apr 24, 2021 02:39 CST Updated 02:39

Roche

Oncology Drug Research, Development, and Manufacturing

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.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.

April 24, 2021 /BioValleyBIOON/ -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the immunotherapy combination of the anti-PD-1 therapy Opdivo (nivolumab) and the anti-CTLA-4 therapy Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). The CHMP’s opinion will now be submitted to the European Commission (EC) for review, which typically renders a final decision within two months.

If approved,Opdivo + Yervoy will become the first new therapy proven to improve survival in patients with malignant pleural mesothelioma (MPM) in Europe in over 15 years.Positive results from the phase 3 CheckMate-743 trial demonstrated that the Opdivo plus Yervoy regimen conferred a significant overall survival (OS) benefit compared with standard-of-care chemotherapy. CheckMate-743 is the first phase 3 trial to show a benefit of first-line immunotherapy for malignant pleural mesothelioma (MPM).

In the United States, the Opdivo + Yervoy regimen was approved by the FDA in October 2020 for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). Notably,Opdivo + Yervoy is the first and only immunotherapy approved for the first-line treatment of unresectable malignant pleural mesothelioma (MPM), and also in the United StatesFDAThe first new systemic therapy approved for the treatment of MPM in the past 15 years.

Opdivo + Yervoy is a unique combination of two immune checkpoint inhibitors with potential synergistic mechanisms of action, targeting two distinct checkpoints (PD-1 and CTLA-4) to help destroyTumorcells. To date, in terms of U.S. regulatory approvals, the Opdivo plus Yervoy combination therapy has been approved for seven therapeutic indications across six cancer types (melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, and malignant pleural mesothelioma). In the European Union, Opdivo plus Yervoy-based combination regimens have been approved for the treatment of three different types of advanced cancers: non-small cell lung cancer (NSCLC),Melanoma. Renal cell carcinoma.

The CHMP’s positive opinion is based on data from the pivotal Phase 3 CheckMate-743 trial, which is the first and only positive Phase 3 immunotherapy trial in the first-line treatment of malignant pleural mesothelioma (MPM). The results demonstrated that, among all randomized patients, dual immunotherapy with Opdivo plus Yervoy (the OY combination) provided a durable survival benefit compared with chemotherapy (pemetrexed plus cisplatin or carboplatin), meeting the primary endpoint of improved overall survival (OS). Its safety profile was consistent with previous studies of Opdivo and Yervoy.

Vice President of Bristol-Myers Squibb, ThoracicTumorDr. Abderrahim Oukessou, Head of Development, stated, “For more than 15 years, no new treatment regimens have been approved to improve survival in malignant pleural mesothelioma (MPM), with most patients surviving only slightly over a year from diagnosis. The CHMP’s positive opinion on the Opdivo plus Yervoy regimen brings us one step closer to addressing the urgent need in Europe for effective, proven therapies for this aggressive cancer. We look forward to launching the first immunotherapy combination, offering patients in the European Union the opportunity for extended survival.”

Malignant Pleural Mesothelioma (MPM, Image Source: ePainAssist.com)

CheckMate-743 is an open-label, multicenter, randomized Phase IIIClinical TrialA total of 605 patients with previously untreated, unresectable malignant pleural mesothelioma (MPM) were enrolled to evaluate the efficacy and safety of Opdivo plus Yervoy dual immunotherapy as first-line treatment, compared with chemotherapy (pemetrexed plus cisplatin or carboplatin). In the study, patients were randomized to receive either Opdivo plus Yervoy (n=303) or chemotherapy (n=302). In the Opdivo plus Yervoy arm, Opdivo was administered at a dose of 3 mg/kg every two weeks, and Yervoy at a dose of 1 mg/kg every six weeks, for up to 24 months or until disease progression or unacceptable toxicity occurred. In the chemotherapy arm, patients received cisplatin 75 mg/m² or carboplatin AUC 5 in combination with pemetrexed 500 mg/m² on a 21-day cycle for up to six cycles, or until disease progression or unacceptable toxicity occurred. The primary endpoint of the study was overall survival (OS) in all randomized patients.

The results showed that the study met its primary endpoint: compared with the chemotherapy group, the Opdivo + Yervoy group demonstrated a significant improvement in overall survival (median OS: 18.1 months vs. 14.1 months), with a 26% reduction in the risk of death (HR = 0.74; 95% CI: 0.61–0.89; p = 0.002). At 2 years, the survival rate was 41% in the Opdivo + Yervoy group versus 27% in the chemotherapy group.

Histology is a recognized prognostic factor for mesothelioma, with non-epithelioid patients generally having a poorer prognosis. In the CheckMate-743 study, Opdivo + Yervoy demonstrated improved overall survival (OS) in both non-epithelioid and epithelioid malignant pleural mesothelioma (MPM), with a greater survival benefit observed in the non-epithelioid subgroup. Specifically, the median OS for epithelioid patients treated with Opdivo + Yervoy was 18.7 months, and for non-epithelioid patients, it was 18.1 months. In contrast, the median OS for epithelioid patients treated with chemotherapy was 16.5 months, and for non-epithelioid patients, it was 8.8 months (epithelioid subgroup: HR=0.86 [95% CI: 0.69, 1.08]; non-epithelioid subgroup: HR=0.46 [95% CI: 0.31, 0.68]).

In this study, the safety profile of Opdivo + Yervoy dual immunotherapy was consistent with previously reported studies, and no new safety signals were observed.

Malignant Pleural Mesothelioma (MPM) is a rare, highly aggressiveTumor, which forms in the lining of the lungs. The most common cause of this disease is asbestos exposure. MPM'sDiagnosisOften delayed, most patients present with advanced or metastatic disease at the time of diagnosis, and the prognosis is generally poor: in previously untreated patients with advanced or metastatic malignant pleural mesothelioma (MPM), the median survival is <1 year, and the 5-year survival rate is approximately 10%.

MPM is a devastating disease with very limited therapeutic progress over the past 15 years. The positive top-line results from the CheckMate-743 trial demonstrated the potential of the Opdivo plus Yervoy combination regimen as first-line treatment for MPM, while also in multipleTumorAnother example demonstrating the efficacy and safety of this dual immunotherapy combination within this category.

Opdivo and Yervoy are both immuno-oncology (I-O) therapies that harness the body’s own immune system to fight cancer by targeting distinct regulatory components within the immune system; Opdivo blocks the PD-1/PD-L1 pathway, while Yervoy targets CTLA-4. Currently, Bristol Myers Squibb is developing the Opdivo plus Yervoy combination immunotherapy for multiple typesTumortreatment.

Opdivo + Yervoy is the United StatesFDAThe only approved dual immunotherapy, this therapy features a potential synergistic mechanism of action targeting two distinct immune checkpoints (PD-1 and CTLA-4) and works in a complementary manner. In terms of U.S. regulatory approvals, the Opdivo + Yervoy combination therapy has been approved for 7 treatment indications across 6 types of cancer (Melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer). (Bioon.com)

Original Source: Bristol Myers Squibb Receives Positive CHMP Opinion Recommendingapproval for Opdivo (nivolumab) Plus Yervoy (ipilimumab) as First-Line Treatment for Unresectable Malignant Pleural Mesothelioma