20 September 2018 - - The European Medicines Agency has validated US-based pharmaceutical company Bristol-Myers Squibb Company's (NYSE: BMY) type II variation application for Empliciti (elotuzumab) in combination with pomalidomide and low-dose dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on the last therapy, the company said.

Validation of the application confirms the submission is complete and begins the EMA's centralized review process.

The application is based on data from ELOQUENT-3, a randomised Phase 2 study evaluating the EPd combination versus pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma.

Data from this study were presented at the 23rd Congress of the European Hematology Association in June.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

The Phase 2 ELOQUENT-3 trial randomized 117 patients with RRMM who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a PI. Patients were randomised 1: 1 to receive either EPd or Pd in 28-day cycles until disease progression or unacceptable toxicity.

Patients in both the EPd and Pd arms received 4 mg of pomalidomide for days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤75 years or >75 years, respectively.

In the EPd arm, Empliciti was administered at the dose of 10 mg/kg IV weekly for the first 2 cycles and 20 mg/kg monthly starting from cycle 3.

Patients randomized to EPd experienced a 46% reduction in risk of disease progression (HR 0.54; 95% CI: 0.34 to 0.86, p=0.0078) compared with patients randomised to Pd alone, with median PFS, the study's primary endpoint, of 10.3 months (95% CI: 5.6 to not estimable) compared with 4.7 months (95% CI: 2.8 to 7.2) in Pd patients.

The PFS benefit experienced among patients randomized to EPd was consistent among patients who had received two to three prior lines of therapy (HR 0.55; 95% CI: 0.31 to 0.98) and four or more prior lines of therapy (HR 0.51; CI 95%: 0.24 to 1.08).

Rates of treatment-related hematologic adverse events were comparable between EPd and Pd groups (38% and 42%, respectively).

The most commonly occurring hematologic AEs among patients receiving EPd were neutropenia, anemia, thrombocytopenia and lymphopenia.

AEs led to discontinuation in 18% of patients in the EPd arm, compared with 24% of patients in the Pd arm.