- First and only immunostimulatory antibody approved in the European Union for multiple myeloma
- Accelerated assessment and approval based on long-term data from ELOQUENT-2, which evaluated Empliciti in combination with Revlimid®(lenalidomide) and dexamethasone (Rd).
- ELOQUENT-2 demonstrated the Empliciti combination delivered a 53% relative improvement in progression-free survival vs. Rd alone at three years (23% vs. 15%)
World pharma today/-press releases/-Bristol-Myers Squibb Company and AbbVie announced that the European Commission has approvedEmpliciti™ (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 evaluated Empliciti 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 theEmpliciti 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 ofEmpliciti 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.”
ELOQUENT-2 (CA204-004) is a Phase 3, open-label, randomized study evaluatingEmpliciti in combination with Rd versus Rd alone in patients with relapsed or refractory multiple myeloma. The trial randomized 646 patients who had received one to three prior therapies. Patients were randomized 1:1 to receive either Empliciti 10 mg/kg in combination with Rd or Rd alone in 4-week cycles until disease progression or unacceptable toxicity. Baseline patient demographics and disease characteristics were well balanced between treatment arms and included a meaningful portion of patients who were ≥ 65 years old, had high-risk cytogenetics and/or were refractory to the most recent line of therapy. The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were PFS, as assessed by hazard ratio, and ORR, as determined by a blinded Independent Review Committee using the European Group for Blood and Marrow Transplantation response criteria.
“As multiple myeloma is largely incurable and is often characterized by a cycle of remission and relapse, there is a critical need for new therapies for patients that work in unique and innovative ways,” said Antonio Palumbo, M.D., study investigator and chief of the Myeloma Unit, Department of Oncology, University of Torino in Torino, Italy. “In clinical trials, Empliciti in combination with lenalidomide and dexamethasone delivered a significant benefit in progression-free survival compared to lenalidomide and dexamethasone alone, which could make a meaningful difference in the lives of patients struggling with this serious disease.”
Discontinuation rates due to adverse reactions were similar across the ERd and Rd arms (8.7%, 12.9%). The most frequent serious adverse reactions (Grade 3-4) in ERd and Rd were lymphopenia (12.7%, 7.4%), pneumonia (10.5%, 8.1%), fatigue (6.4%, 6.2%), diarrhea (3.7%, 3.1%) and deep vein thrombosis (3.5%, 1.7%). The most common adverse reactions in ERd and Rd (>20%), 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%) and upper respiratory tract infection (25.2%, 22.7%).
Infusion reactions occurred in 10% of patients treated with ERd; these adverse reactions were Grade 3 or lower (Grade 3, 1%; Grade 4, 0%). In the trial, 1% of patients discontinued due to infusion reactions, and 5% of patients required interruption of the administration of Empliciti for a median of 25 minutes.
About Multiple Myeloma
Multiple myeloma is a hematologic, or blood, cancer that develops in the bone marrow. It occurs when a plasma cell, a type of cell in the soft center of bone marrow, becomes cancerous and multiplies uncontrollably. Common symptoms of multiple myeloma include bone pain, fatigue, kidney impairment and infections.
Despite advances in multiple myeloma treatment over the last decade, less than half of patients survive for five or more years after diagnosis. Patients often experience a cycle of remission and relapse, and once a patient first relapses, their prognosis worsens with progressively faster relapses through each subsequent line of therapy. It is estimated that annually, more than 114,200 new cases of multiple myeloma are diagnosed, and more than 80,000 people die from the disease globally.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now considered a major treatment modality alongside surgery, radiation and chemotherapy for certain types of cancer.
We have a comprehensive clinical portfolio of investigational and approved Immuno-Oncology agents, many of which were discovered and developed by our scientists. We pioneered the research leading to the first regulatory approval for the combination of two Immuno-Oncology agents and continue to study the role of combinations in cancer.
Our collaboration with academia, as well as small and large biotech companies, is responsible for researching the potential Immuno-Oncology and non-Immuno-Oncology combinations, with the goal of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival expectations in hard-to-treat cancers and the way patients live with cancer.
Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.
Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.
Empliciti in combination with lenalidomide and dexamethasone is approved in the United States, and the safety and efficacy of Empliciti is being evaluated by other health authorities.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world’s most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com.
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