Date: 2016-05-13
Type of information: Granting of a Market Authorisation in the EU
Product name: Empliciti®
Compound: elotuzumab - BMS-90160
Therapeutic area: Cancer - Oncology - Rare diseases
Action mechanism: monoclonal antibody. Elotuzumab is an investigational immunostimulatory antibody targeted against Signaling Lymphocyte Activation Molecule (SLAMF7), a cell-surface glycoprotein that is highly and uniformly expressed on myeloma cells and Natural Killer (NK) cells, but is not detected on normal solid tissues or on hematopoietic stem cells. Elotuzumab is being investigated to determine whether the compound may selectively target myeloma cells. It is believed that elotuzumab works through a dual mechanism of action: binding to SLAMF7 on NK cells, directly activating them and binding to SLAMF7 on myeloma cells, flagging them for NK cell recognition and destruction. Elotuzumab is being studied as a monotherapy in smodering myeloma and in combination with other therapies in first-line and relapsed or refractory multiple myeloma. A clinical development program for the agent is underway, including Phase 3 trials in first-line multiple myeloma (ELOQUENT-1) and relapsed or refractory multiple myeloma (ELOQUENT-2). Elotuzumab is also being investigated in a randomized Phase 2 study of bortezomib and dexamethasone in relapsed or refractory multiple myeloma. In May 2014, the FDA granted elotuzumab Breakthrough Therapy Designation for use in combination with one of the chemotherapy treatments for multiple myeloma (lenalidomide, used in combination with dexamethasone) in patients who have received one or more prior treatments. BMS and AbbVie are co-developing elotuzumab, with BMS leading the commercialization of the agent.
Company: BMS (USA - NY) Abbvie (USA - IL)
Disease: multiple myeloma
Latest news: * On January 28, 2016, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for Empliciti® (elotuzumab) for the treatment of multiple myeloma. It is to be used in combination with lenalidomide and the anti-inflammatory medicine dexamethasone for the treatment of patients who have received at least one prior therapy. The CHMP reviewed Empliciti® under EMA’s accelerated assessment programme. Accelerated assessment is one of the Agency’s main mechanisms to facilitate earlier access by patients to medicines that fulfill unmet medical needs. The CHMP’s recommendation is based on a randomised, open-label Phase 3 study evaluating Empliciti® in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The trial enrolled 646 patients whose multiple myeloma came back after, or did not respond to, previous treatment. In patients also taking Empliciti®, the disease progressed more slowly (difference in medians of 4.2 months) than in patients taking only lenalidomide and dexamethasone. In addition, 78.5% of patients taking Empliciti® with lenalidomide and dexamethasone saw a complete or partial shrinkage of their tumours compared to 65.5% in those only taking lenalidomide and dexamethasone. The most common side effects of Empliciti® are infusion-related reactions, diarrhoea, cough, herpes zoster (shingles), nasopharyngitis (infection of the nose and throat), pneumonia, upper respiratory tract infection, lymphopenia (lowered counts of a type of white blood cell called lymphocytes) and weight loss. * On November 30, 2015, the FDA granted approval for Empliciti® (elotuzumab) in combination with two other therapies to treat people with multiple myeloma who have received one to three prior medications. Empliciti® activates the body’s immune system to attack and kill multiple myeloma cells. It is approved in combination with another FDA-approved treatments for multiple myeloma Revlimid® (lenalidomide) and dexamethasone. The safety and efficacy of Empliciti® were tested in a randomized, open-label clinical study of 646 participants whose multiple myeloma came back after, or did not respond to previous treatment. Those taking Empliciti® plus Revlimid® and dexamethasone experienced a delay in the amount of time before their disease worsened (19.4 months) compared to participants taking only Revlimid and dexamethasone (14.9 months). Additionally, 78.5 percent of those taking Empliciti with Revlimid and dexamethasone saw a complete or partial shrinkage of their tumors compared to 65.5 percent in those only taking Revlimid and dexamethasone. The most common side effects of Empliciti® are fatigue, diarrhea, fever (pyrexia), constipation, cough, nerve damage resulting in weakness or numbness in the hands and feet (peripheral neuropathy), infection of the nose and throat (nasopharyngitis), upper respiratory tract infection, decreased appetite and pneumonia. * On September 1, 2015, BMS and AbbVie announced the FDA has accepted for priority review the Biologics License Application (BLA) for Empliciti® (elotuzumab) for the treatment of multiple myeloma as combination therapy in patients who have received one or more prior therapies. BMS has proposed the name Empliciti which, if approved by health authorities, will serve as the brand name for elotuzumab. The filing acceptance is primarily supported by data from the ELOQUENT-2 trial, a Phase 3, randomized, open-label study, which evaluated Empliciti® in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone. The results of this trial were published in The New England Journal of Medicine on June 2. Additionally, the filing was supported by data from study CA204-009, a Phase 2, randomized, open-label study which evaluated Empliciti with bortezomib and dexamethasone versus bortezomib and dexamethasone alone. These Phase 2 results were presented in an oral session (Abstract #S103) at the 20th Congress of the European Hematology Association (EHA). * On July 27, 2015, BMS and AbbVie announced the European Medicines Agency (EMA) validated for review the Marketing Authorization Application (MAA) for Empliciti® (elotuzumab) for the treatment of multiple myeloma as combination therapy in adult patients who have received one or more prior therapies. The application was granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The MAA is primarily supported by data from two randomized clinical trials, each combining Empliciti® with a different standard of care regimen for multiple myeloma. ELOQUENT-2, a Phase 3, randomized, open-label study, evaluated Emplicit®i in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone. Additionally, a Phase 2, randomized, open-label study (Study CA004-009) evaluated Empliciti® with bortezomib and dexamethasone versus bortezomib and dexamethasone alone. These Phase 2 results were presented in an oral session (Abstract #S103) at the 20th Congress of the European Hematology Association (EHA). * On May 19, 2014, BMS and AbbVie announced that the FDA has granted elotuzumab Breakthrough Therapy Designation for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received one or more prior therapies. The designation is based on findings from a randomized Phase 2, open-label study that evaluated two dose levels of elotuzumab in combination with lenalidomide and low-dose dexamethasone in previously-treated patients, including the 10 mg/kg dose that is being studied in Phase 3 trials. Data from the Phase 2 trial were most recently presented at the 18th Annual Congress of the European Hematology Association (EHA) in 2013. * On July 11, 2012, the Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion recommending elotuzumab for designation as an orphan medicinal product for the treatment of multiple myeloma. A phase 3 trial is currently ongoing to determine whether the addition of elotuzumab to lenalidomide/low-dose dexamethasone will increase the progression free survival (PFS) in patients with previously untreated multiple myeloma (NCT01335399).
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: 2015-11-30
UE authorization: 2016-05-13
Favourable opinion UE: 2016-01-28
Favourable opinion USA:
Orphan status USA: 2011-09-01
Orphan status UE: 2012-08-09
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
