REVLIMID approved by the European Commission for the treatment of adult patients with previously untreated multiple myeloma

Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation, has announced that the European Commission (EC) has approved REVLIMID® (lenalidomide) for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant.

The REVLIMID Marketing Authorisation has been updated to include this new indication in multiple myeloma, building upon the already approved indication of REVLIMID in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.

Multiple myeloma is a persistent and life-threatening blood cancer that is characterised by tumour proliferation and suppression of the immune system.¹ It is a rare but deadly disease: around 38,900 people were newly diagnosed with multiple myeloma in Europe in 2012, and 24,300 people died from the disease in the same year.² On average, multiple myeloma is diagnosed in people 65-74 years of age,³ and the majority of newly diagnosed patients may not be eligible for more aggressive treatment options such as high-dose chemotherapy with stem cell transplant.⁴

Professor Thierry Facon, Services des Maladies du Sang, Hôpital Claude Huriez, and CHRU Lille, France, says: "Having a new treatment option now available for patients newly diagnosed with multiple myeloma is a real step forward. Treating patients continuously until disease progression is supported by several clinical studies, and will have an important impact on how we manage the disease over the long-term."

"We are very pleased that physicians can now offer their patients a new and different treatment option," said Tuomo Pätsi, President of Celgene in Europe, the Middle East and Africa (EMEA). "Multiple myeloma is rare, but it is devastating for those who have it, and it has a major impact on their friends and family too. We have seen significant progress in the treatment of the disease over the years, with an improvement of more than 50% in 5-year survival rates, but there continues to be a need for innovative new approaches to turn deadly diseases, like this one, into manageable, long-term, chronic conditions."

The EC decision in newly diagnosed multiple myeloma was based on the results of two pivotal studies: MM-020 (also known as the FIRST trial) and MM-015.

• The FIRST study, MM-020,⁵ was one of the largest phase III, multi-centre, open-label, randomised studies in patients newly diagnosed with multiple myeloma and not eligible for stem cell transplantation, including 1,623 patients. It compared lenalidomide plus dexamethasone administered in 28-day cycles until disease progression (Rd), with Rd for 72 weeks (18 cycles; Rd18) and melphalan-prednisone-thalidomide (MPT) for 72 weeks. Progression-free survival (PFS; study primary endpoint) was significantly improved in patients treated continuously with Rd, compared with those receiving MPT (primary comparison, p < 0.0001) or Rd18 (p < 0.0001). Median overall survival (OS) in patients receiving Rd continuous therapy was 58.9 months, vs. 48.5 months for patients treated with MPT (HR 0.75; 95% CI 0.62, 0.90), based on a March 3, 2014 interim OS analysis. The numbers of patients experiencing any grade 3 or 4 adverse event were similar in each group. The most frequent grade 3 or 4 adverse events were neutropenia, anaemia and infections.
• MM-015⁵ was a multi-centre, randomised, double-blind, placebo-controlled phase III study of 459 patients that compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone- lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients ≥65 years or older with newly diagnosed multiple myeloma. Progression-free survival (PFS; study primary endpoint) was significantly improved in patients treated with MPR-R when compared with MPR and MP (p < 0.001 for comparisons of MPR-R over MPR and MP). In the MM-015 study, overall survival was not significantly improved when compared across any treatment arm. During induction, the most frequent adverse events were hematologic (including neutropenia, thrombocytopenia, and anaemia). During the maintenance phase, the incidence of new or worsened grade 3 or 4 adverse events was low (0 to 6%).

The EC decision for the use of REVLIMID in newly diagnosed multiple myeloma in adult patients ineligible for transplantation follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) in December 2014. It is the second European Commission approval Celgene has received this year, following the approval of OTEZLA®, the first phosphodiesterase-4 (PDE-4) inhibitor for use in psoriasis and psoriatic arthritis, in January 2015. A CHMP positive opinion was also issued in January for use of the company's oncology drug ABRAXANE®, in non-small cell lung cancer.

Celgene announced on 18 February 2015 that the U.S. Food and Drug Administration (FDA) has expanded the existing indication for REVLIMID (lenalidomide) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma in the U.S.

About REVLIMID®

In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. In the European Union, REVLIMID is approved for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. REVLIMID is 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 anaemia due to low- or intermediate-1-risk 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 myelodysplastic syndromes 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. In Switzerland, REVLIMID is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.