Bristol-Myers Squibb Company and AbbVie have announced that the European Commission has approved Empliciti™ (elotuzumab) for the treatment of multiple myeloma as combination therapy with Revlimid® (lenalidomide) and dexamethasone in patients who have received at least one prior therapy. Empliciti is now the first and only immunostimulatory antibody approved for multiple myeloma in the European Union (EU).
The approval is based on data from the randomized, open-label, Phase 3 ELOQUENT-2 study, which evaluatedEmpliciti in combination with lenalidomide and dexamethasone (ERd) versus lenalidomide and dexamethasone (Rd) alone. The co-primary endpoints of this study, progression-free survival (PFS) as assessed by hazard ratio (HR) and overall response rate (ORR), were achieved, with extended follow-up data showing a 53% relative improvement in PFS rate at three years (23% versus 15%). Additionally, a pre-specified interim analysis for overall survival (OS) found a positive trend favoring the Empliciti combination versus Rd alone (HR=0.77 [95% CI: 0.61, 0.97, p=0.0257]), though at the time of the interim analysis, the OS endpoint had not reached the pre-determined threshold for statistical significance. Patients will continue to be followed for survival, and the final analysis is pending. Empliciti with lenalidomide and dexamethasone is associated with the following Warnings and Precautions: infusion reactions, infections, second primary malignancies, hepatotoxicity, interference with determination of complete response, pregnancy/females and males of reproductive potential, and adverse reactions. Please see detailed Important Safety Information below.
“At Bristol-Myers Squibb, we are committed to delivering pioneering medicines with the goal of revolutionizing the way cancer is treated for patients who inspire our work each and every day,” said Emmanuel Blin, senior vice president and head of Commercialization, Policy and Operations, Bristol-Myers Squibb. “With the approval of Empliciti in the EU, we are proud to extend our Immuno-Oncology science to multiple myeloma patients in Europe who have received at least one prior therapy.”
In ELOQUENT-2, Empliciti was evaluated in patients who had received one to three prior therapies. The study demonstrated that the ERd regimen resulted in a 32% reduction in the risk of disease progression or death compared to Rd alone (HR=0.68 [97.61% CI: 0.55, 0.85, p=0.0001]). The ERd regimen also showed a 21% relative improvement in PFS rate at one year (68% versus 56%) and a 50% relative improvement in PFS rate at two years (39% versus 26%) compared to Rd alone. The ERd regimen demonstrated a significant improvement in ORR of 78.5% (95% CI: 73.6-82.9; p=0.0002) versus 65.5% in the Rd arm (95% CI: 60.1-70.7). The extended follow-up analysis also showed ERd had a median delay of one year in the time to next treatment compared to Rd alone: 33.35 months (95% CI: 26.15, 40.21) versus 21.22 months (95% CI: 18.07, 23.20) (HR=0.62 [95% CI: 0.50, 0.77]). These data were initially reported at the 57th American Society of Hematology Annual Meeting in December 2015.
The most common adverse reactions (all grades) in ERd and Rd (>10%), respectively, were diarrhea (59.2%, 49.3%), pyrexia (43.0%, 27.7%), fatigue (40.0%, 34.7%), cough (33.2%, 20.3%), nasopharyngitis (29.5%, 27.7%), upper respiratory tract infection (25.2%, 22.7%), lymphopenia (17.6%, 13.6%), headache (17.2%, 9.6%), pneumonia (15.6%, 12.9%) and herpes zoster (10.0%, 5.7%).
“Today’s decision of the European Commission is excellent news for relapsed and refractory multiple myeloma patients,” said Sarper Diler, President of Myeloma Patients Europe. “Multiple myeloma has had a difficult-to-treat history, and at Myeloma Patients Europe, we are committed to ensuring these patients living in any European country are able to access new, innovative medicines, like Empliciti.”
“Empliciti represents an important new treatment option for patients with multiple myeloma and healthcare providers who are treating this cancer in Europe,” said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. “AbbVie is proud to be part of the team that developed Empliciti and pleased to be partnering with Bristol-Myers Squibb to bring this new therapy to previously treated multiple myeloma patients.”