BMS Withdraws Opdivo (nivolumab) Plus Yervoy (ipilimumab) EU Application for First-Line Advanced NSCLC Following CHMP Feedback
Bristol-Myers Squibb
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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.
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Bristol-Myers Squibb (BMS) recently announced that it has withdrawn its application for the use of Opdivo in combination with Yervoy as first-line treatment for advanced non-small cell lung cancer (NSCLC) in the European Union.
The application, initially submitted in 2018, was based on data from the Phase 3 CheckMate-227 clinical trial. At that time, the data derived from a progression-free survival analysis of first-line treatment in patients with non-small cell lung cancer (NSCLC) whose tumors had a tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb). Subsequently, Bristol-Myers Squibb (BMS) revised the data supporting the application to include results from Part 1a of the CheckMate-227 trial, which demonstrated a significant overall survival benefit of Opdivo in combination with Yervoy versus chemotherapy in NSCLC patients with tumor PD-L1 expression ≥1%.
Although the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency acknowledged the integrity of the trial data, the CHMP ultimately concluded that “a comprehensive assessment of the application could not be performed” and rejected the application.
BMS subsequently stated that it has no plans to resubmit the application in the European Union.
CheckMate-227 is an open-label, phase 3 clinical trial primarily composed of two parts, comparing Opdivo-based regimens with platinum-doublet chemotherapy as first-line treatment in patients with advanced non-squamous and squamous NSCLC.
Part 1 of the trial comprises: Part 1a, comparing Opdivo plus Yervoy or Opdivo monotherapy with chemotherapy in patients with PD-L1–expressing tumors; and Part 1b, comparing Opdivo plus Yervoy or Opdivo in combination with chemotherapy with chemotherapy alone in patients with non–PD-L1–expressing tumors.
In Part 1, Opdivo + Yervoy had two co-primary endpoints relative to chemotherapy: overall survival (OS) in patients with PD-L1–expressing tumors (assessed in patients from Part 1a); and progression-free survival (PFS) in patients with tumor mutational burden (TMB) ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients from Parts 1a and 1b). The results showed that both co-primary endpoints were met. Compared with chemotherapy, Opdivo + Yervoy achieved improved PFS in patients with high TMB (≥10 mut/Mb), regardless of PD-L1 expression, and demonstrated improved OS in patients with PD-L1 expression ≥1%.
Part 2 of the trial evaluated Opdivo in combination with chemotherapy versus chemotherapy alone in patients regardless of PD-L1 expression status. However, in Part 2, the primary endpoint of improved overall survival (OS) was not met for Opdivo plus chemotherapy compared with chemotherapy alone in patients with non-squamous NSCLC.
Samit Hirawat, M.D., Chief Medical Officer at Bristol-Myers Squibb (BMS), stated, “CheckMate -227 is a robust Phase 3 clinical study involving more than 2,220 patients. In the first-line treatment of patients with non-small cell lung cancer (NSCLC), Opdivo in combination with Yervoy demonstrated statistically and clinically significant overall survival benefits compared to chemotherapy. The observed durable survival advantage represents an important outcome for patients, and we are disappointed by the CHMP’s decision.”
In 2014, Opdivo became the first PD-1 inhibitor approved for marketing worldwide, with Merck’s Keytruda following closely behind, initiating a competitive rivalry between the two PD-1 antibodies. In 2018, Keytruda’s quarterly sales surpassed those of Opdivo for the first time, and the gap has since widened progressively. According to data from the first three quarters of 2019, Opdivo generated $5.441 billion in sales, whereas Keytruda reached $7.973 billion. In response, Bristol-Myers Squibb (BMS) has continuously expanded the indications for Opdivo, including combination therapies. In October 2015, the Opdivo plus Yervoy combination regimen became the first approved immuno-oncology combination therapy for metastatic melanoma; it was subsequently approved for the treatment of advanced renal cell carcinoma.
In January 2020, the U.S. FDA granted priority review for Opdivo + Yervoy as a first-line treatment for NSCLC, based on data from Part 1 of the CheckMate-227 trial.
Furthermore, the ongoing CheckMate-9LA trial is evaluating Opdivo plus Yervoy in combination with a limited course of chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Bristol-Myers Squibb plans to submit regulatory applications in the United States, Europe, and other markets following the positive interim results from CheckMate-9LA.
Reference Source: Bristol-Myers Squibb Withdraws European Application of Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer
*Disclaimer: This article was written by an author contributing to Sina Medical News. The views expressed are solely those of the author and do not represent the position of Sina Medical News.