Date: 2016-11-22
Type of information: Granting of a Market Authorisation in the EU
Product name: Opdivo®
Compound: nivolumab
Therapeutic area: Cancer - Oncology - Transplantation
Action mechanism: monoclonal antibody. 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: Hodgkin lymphoma Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab vedotin
Latest news: * On November 22, 2016, BMS announced the European Commission approved Opdivo® (nivolumab) for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin. Opdivo® is now the first and only PD-1 inhibitor approved for a hematologic malignancy in the European Union (EU). This approval allows for the expanded marketing of Opdivo® in relapsed or refractory cHL in all 28 Member States of the EU. The approval is based on an integrated analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials, evaluating patients with relapsed or refractory cHL after ASCT and treatment with brentuximab vedotin. In the subset of patients in the efficacy population (n=95), the primary endpoint of objective response rate (ORR) as assessed by an independent radiologic review committee was 66% (95% CI: 56-76; 63/95 patients). The percentage of patients with a complete response was 6% (95% CI: 2-13; 6/95 patients), and the percentage of patients with a partial response was 60% (95% CI: 49-70; 57/95 patients). At 12 months, the progression-free survival rate was 57% (95% CI: 45-68). Opdivo is associated with warnings and precautions including immune-related: pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, endocrinopathies, rash, and other adverse reactions; infusion reactions, and complications of allogeneic hematopoietic stem cell transplantation (HSCT) in cHL after Opdivo. In the integrated analysis of data from CheckMate -205 and CheckMate -039, the median time to response was 2.0 months (range 0.7-11.1), and among responders, the duration of response was maintained over time for a median of 13.1 months (95% CI: 9.5-NE; range 0.0+, 23.1+). Stable disease was observed in 23% of patients. In a post-hoc analysis of the 80 patients in CheckMate -205 cohort B, it was found 37 patients had no response to prior brentuximab vedotin treatment. Among these 37 patients, treatment with Opdivo resulted in an ORR of 59.5% (22/37), and the median duration of response was 13.14 months. The safety of Opdivo in cHL was evaluated in 263 adult patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Among these patients (total safety population: n=263), serious adverse events (AEs) occurred in 21% of patients. The most common serious AEs (reported in at least 1% of patients) were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%). Twenty-three percent of patients had a dose delay for an AE, and 4.2% of patients discontinued treatment due to AEs. Six out of 40 patients died from complications of allogeneic HSCT after Opdivo, and these 40 patients had a median follow-up from subsequent allogeneic HSCT of 2.9 months (range: 0-22). * On April 14, 2016, BMS announced that the FDA accepted a supplemental Biologics License Application (sBLA), which seeks to expand the use of Opdivo® to patients with classical Hodgkin lymphoma after prior therapies. The application included CheckMate -205 data, which evaluated Opdivo® in classical Hodgkin lymphoma patients who have received autologous stem cell transplant and brentuximab vedotin. Data from this phase 2 study are expected to be presented at a medical meeting later this year. The FDA granted the application a priority review and previously granted Opdivo® Breakthrough Therapy Designation for classical Hodgkin lymphoma on May 14, 2014 (see below). * On March 30, 2016, BMS announced that the European Medicines Agency (EMA) validated a type II variation application, which seeks to extend the current indications for Opdivo® to include the treatment of patients with classical Hodgkin lymphoma (cHL) after prior therapies. The application included CheckMate -205 data, which evaluated Opdivo® in cHL patients who have received autologous stem cell transplant and brentuximab vedotin. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process. CheckMate -205 is a Phase 2 study evaluating the safety and efficacy of Opdivo® in patients with relapsed or refractory cHL. The results of this trial are expected to be presented at a medical meeting later this year. * On August 7, 2014, the FDA has approved the granting of an orphan designation for nivolumab for the treatment of Hodgkin lymphoma. * On May 14, 2014, BMS announced that the FDA has granted the investigational PD-1 immune checkpoint inhibitor nivolumab Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. The designation is based on data from a cohort of patients with HL in the company’s ongoing Phase 1b study of relapsed and refractory hematological malignancies.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2016-11-22
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2014-08-07
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
