The European Medicines Agency has validated Bristol-Myers Squibb’s application for Empliciti (elotuzumab), in combination with Pomalyst (pomalidomide) and low-dose dexamethasone, for the treatment of adults with multiple myeloma.
Validation confirms that the submission is complete and signals the beginning of the EMA’s review process.
The company’s type-II variation application is intended for the treatment of patients who have received at least two previous therapies, including Revlimid (lenalidomide), by Celgene, and a type of therapy called a proteasome inhibitor — which cause the buildup of faulty proteins inside cells, triggering their death — and showed disease progression on the last therapy.
“Given the need for new treatment options for patients with multiple myeloma, we look forward to working closely with the EMA as they review this application,” Fouad Namouni, MD, Bristol-Myers Squibb’s head of the oncology development, said in a press release. “It is our hope that this new Empliciti-based combination will soon become available for patients in the European Union with multiple myeloma.”
Bristol-Myers Squibb’s application is based on results of the randomized Phase 2 ELOQUENT-3 clinical trial (NCT02654132), which assessed the triple combination versus Celgene’s Pomalyst (marketed as Imnovid in Europe) and dexamethasone alone in 117 patients with relapsed or refractory multiple myeloma.
Of these patients, 60 were randomly assigned to the triple therapy and 57 to Pomalyst and dexamethasone alone, which was the control group.
Empliciti was administered directly into the bloodstream at 10 mg/kg weekly over the first two cycles — lasting four weeks each — and 20 mg/kg monthly starting from cycle three. Revlimid was given at a daily 4 mg dose and dexamethasone at a weekly equivalent of 20 mg, for patients older than 75, or 40 mg, for patients 75 or younger.
Results, presented at the 23rd Congress of the European Hematology Association in June, showed that adding Empliciti to Pomalyst and dexamethasone significantly delayed disease worsening or death. Patients on the triple therapy lived for a median of 10.3 months without their disease progressing versus 4.7 months for those in the control group, representing a 46% reduction in the risk of disease progression or death.
Delayed disease progression was consistent across patients who failed to respond to two to three and four or more previous treatments with Revlimid and a proteasome inhibitor. Additionally, the overall response rate was superior in the triple combination — 53% versus 26%.
The study, conducted by Bristol-Myers Squibb, in collaboration with Celgene and AbbVie — which co-develops Empliciti — also demonstrated that the triple therapy had an acceptable safety profile. Rates of adverse events (38% and 42%) and the percentage of patients stopping treatment (18 and 24%) were comparable between the two groups.
In August, the triple combination was granted priority review by the U.S. Food and Drug Administration as a treatment for the same patient population.
Empliciti is an antibody that specifically targets and binds to a molecule known as SLAMF7, which is found on the surface of both myeloma cells and a type of immune cell called natural killer cells, which help destroy tumors. The potential medication binds to natural killer cells to activate the immune system and to myeloma cells to tag them for natural killer cell-mediated destruction.