Type of information: Granting of a Market Authorisation in the EU
Product name: Opdivo®
Therapeutic area: Cancer - Oncology
Action mechanism: monoclonal antibody/immune chekcpoint inhibitor. Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. BMS is investigating whether by blocking this pathway, nivolumab would enable the immune system to resume its ability to recognize, attack and destroy cancer cells.
Company: BMS (USA - NY)
Disease: recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after platinum based therapy
- • On April 28, 2017, BMS announced that the European Commission has approved Opdivo® (nivolumab) as monotherapy for the treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy. Opdivo® is the first and only Immuno-Oncology (I-O) treatment that demonstrated in a Phase 3 trial a significant improvement in overall survival for these patients. The approval was based on results from CheckMate -141, a global Phase 3, open-label, randomized trial, first published in The New England Journal of Medicine last October, which evaluated Opdivo versus investigator’s choice of therapy in patients aged 18 years and above with recurrent or metastatic, platinum-refractory SCCHN who had tumor progression during or within six months of receiving platinum-based therapy administered in the adjuvant, neo-adjuvant, primary or metastatic setting. Investigator’s choice of therapy included methotrexate, docetaxel, or cetuximab. The primary endpoint was OS. The trial’s secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).In the interim analysis of the pivotal trial, Opdivo demonstrated statistically significant improvement in OS with a 30% reduction in the risk of death (HR=0.70 [95% CI: 0.53-0.92; p=0.0101]), and a median OS of 7.5 months (95% CI: 5.5-9.1) for Opdivo compared with 5.1 months (95% CI: 4.0-6.0) for the investigator’s choice arm. There were no statistically significant differences between the two arms for PFS (HR=0.89; 95% CI: 0.70, 1.13) or ORR (13.3% [95% CI: 9.3, 18.3] vs 5.8% [95% CI: 2.4, 11.6] for Opdivo and investigator’s choice, respectively. The EC approval was based on updated study results, which will be presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO).
Patient reported outcomes (PROs) were evaluated using the following European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Assessment: EORTC QLQ-C30, EORTC QLQ-H&N35, and 3-level EQ-5D instruments. Patients treated with Opdivo exhibited stable PROs, while those assigned to investigator’s choice therapy exhibited significant declines in functioning (e.g., physical, role, social) and health status as well as increased symptomatology (e.g., fatigue, dyspnoea, appetite loss, pain and sensory problems).
The safety profile of Opdivo in CheckMate -141 was consistent with prior studies in patients with melanoma and non-small cell lung cancer. Serious adverse reactions occurred in 49% of patients receiving Opdivo. The most frequent serious adverse reactions reported in at least 2% of patients receiving Opdivo were pneumonia, dyspnea, aspiration pneumonia, respiratory failure, respiratory tract infection, and sepsis.
- • On March 24, 2017, the Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Opdivo® as monotherapy for the treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy. This is the first CHMP positive opinion to recommend a PD-1 inhibitor for this type of treatment for SCCHN. Opdivo® is already approved by the EC for six indications in four distinct tumor types.
- • On July 18, 2016, BMS announced U.S. and European marketing applications to expand the use of Opdivo® for patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) were accepted for filing by the FDA and validated by the European Medicines Agency (EMA). In the U.S., the FDA accepted the Company’s supplemental Biologics License Application (sBLA) for Opdivo® in SCCHN with priority review, and previously granted the agent Breakthrough Therapy Designation in April 2016. The projected FDA action date is November 11, 2016. In Europe, the EMA validated a type II variation application for the same patient population. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process. Both U.S. and European submissions were based on CheckMate -141, a pivotal Phase 3 open-label, randomized trial, that evaluated the overall survival (OS) of Opdivo® in patients with SCCHN after platinum therapy compared to investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab). Based on a planned interim analysis, this trial was stopped early in January 2016 because an assessment conducted by the independent Data Monitoring Committee concluded the study met its primary endpoint of OS in patients receiving Opdivo compared to investigator’s choice of therapy. Overall survival results from CheckMate -141 were first presented at the 2016 Annual Meeting of the American Association for Cancer Research.
- • On April 25, 2016, BMS announced that the FDA has granted Breakthrough Therapy Designation to Opdivo® for the potential indication of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after platinum based therapy. The designation is based on results of CheckMate -141, a Phase 3, open-label, randomized trial evaluating Opdivo versus investigator’s choice of therapy in patients with recurrent or metastatic SCCHN with tumor progression within six months of platinum therapies in the adjuvant, primary, recurrent or metastatic setting. This trial was stopped early in January 2016 because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its primary endpoint of overall survival.
- This is the fifth Breakthrough Therapy Designation granted for Opdivo® by the FDA, with previous Breakthrough Therapy Designation indications including patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab, previously treated advanced melanoma, previously treated non-squamous non-small cell lung cancer, and advanced or metastatic renal cell carcinoma.
Submission of marketing authorization application USA : 2016-07-18
Submission of marketing authorization application UE: 2016-07-18
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
UE authorization: 2017-04-28
Favourable opinion UE: 2017-03-24
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: