BOUDRY, Switzerland & TOKYO–(BUSINESS WIRE) — Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ:CELG) today announced that REVLIMID® (lenalidomide), a cancer medicine that is administered orally, has been granted full marketing authorization by Japan’s Ministry of Health, Labour and Welfare (MHLW) for use in combination with dexamethasone as a treatment for patients newly diagnosed with multiple myeloma. This marketing authorization expands upon the approval of REVLIMID in 2010 for the treatment of patients with relapsed or refractory multiple myeloma.
“The approval of REVLIMID as an option for use in newly diagnosed patients with multiple myeloma represents an important step forward in the interest of patients, health care and society,” said Joe Melillo, VP and General Manager, Celgene Japan.
The approval was based on safety and efficacy results from an international phase III study, the FIRST trial (MM-020/IFM 07-01) as the pivotal study, as well as a confirmatory Japanese phase II study (MM-025).
The FIRST trial evaluated continuous REVLIMID in combination with dexamethasone (Rd Continuous) until disease progression versus melphalan, prednisone and thalidomide (MPT) for 18 months as the primary analysis, and a fixed duration of 18 cycles of Rd (Rd18) as a secondary analysis, in 1,623 newly diagnosed patients who were not candidates for stem cell transplant.
In this randomized, open-label, three-arm trial, median progression-free survival (PFS), the length of time a patient lives from study randomization to disease progression or death was the primary endpoint of the study. PFS was significantly longer for patients receiving Rd Continuous (25.5 months) than for those treated with MPT (21.2 months; HR=0.72; p=0.0001). Median overall survival (OS) in the two groups was 58.9 months and 48.5 months, respectively (HR 0.75; 95% CI 0.62, 0.90) based on a March 3, 2014 interim OS analysis. Patients in the Rd Continuous arm had a 25% reduction in the risk of death compared to patients in the MPT arm.
Safety results showed that adverse reactions reported in ≥20% of NDMM patients in the Rd Continuous, Rd18 or MPT arms included diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neutropenia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), decreased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).
The most frequently reported Grade 3 or 4 events in the Rd Continuous arm (until disease progression) included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.6%) and hyperglycemia (5.3%).
MM-025 is a multicenter, open-label, single-arm registration trail in 26 transplantation-ineligible newly diagnosed patients. The trial evaluated the efficacy and safety of continuous REVLIMID in combination with dexamethasone (Continuous Rd) until disease progression in 26 newly diagnosed patients who were not candidates for stem cell transplant.
In this study, overall response rate, the primary endpoint of the study was 87.5%, based on a July 15, 2014 analysis. At a median duration of follow-up of 14.2 months, the median PFS had not been reached.
Safety results from the study were similar to the FIRST trial. The most frequently reported grade 3 or 4 adverse events were neutropenia (23.1%), anemia (19.2%), thrombocytopenia (15.4%), leukopenia (11.5%), lymphopenia (11.5%), rash (11.5%), and pneumonia, hypertension, hypoalbuminemia, hyponatremia, and hypophosphatemia (each at 7.7%). At the time of the study analysis, no deaths from adverse events or second primary malignancies had been reported.
In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.
REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.
In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib
December 21, 2015