Celgene has confirmed that Pomalidomide Celgene® - (pomalidomide), a new oral blood cancer therapy, has been granted Marketing Authorisation by the European Medicines Agency and is now available in the UK and Ireland. Pomalidomide is for use in combination with dexamethasone for the treatment of adults with relapsed and refractory multiple myeloma (rrMM) who have received at least two prior therapies including both lenalidomide and bortezomib, and have demonstrated disease progression while on their last therapy.
The authorisation is based on compelling results from the pivotal Phase III MM-003 study, which demonstrated significant advantages for pomalidomide in progression-free survival and overall survival when compared to high dose dexamethasone alone.[1],[2]
"Today's decision represents a significant milestone for people with multiple myeloma," said Professor Steve Schey, lead investigator for the MM-003 study and Consultant Haematologist at King's College Hospital, London. "These patients have exhausted multiple therapies, including current standards of care. The introduction of pomalidomide gives these patients another option and can potentially help extend remissions in this incurable disease."
Multiple myeloma is the second most common blood cancer[3] and affects an estimated 9,900 people in the UK and Ireland.[4] The disease causes plasma cells to replicate uncontrollably and accumulate in the bone marrow, disrupting the production of normal blood cells. Nearly all individuals diagnosed with multiple myeloma will eventually relapse and require treatment with an alternative therapy.[5] For this reason, it is crucial that new and effective options continue to be made available to them to enable continued disease control.[2]
The European Medicines Agency's decision was based on the results from the MM-003 study, a Phase III, multi-centre, randomised (2:1), open-label study in 455 patients.[7] The results demonstrated significantly improved median progression-free survival of 3.6 months; p<0.001 for patients with rrMM who were treated with pomalidomide plus low-dose dexamethasone, compared with 1.8 months; p<0.001 for those treated with high-dose dexamethasone only (data cutoff 07/09/12).7 Median overall survival was also significantly improved for the pomalidomide plus low-dose dexamethasone arm (12.7 months), compared with high-dose dexamethasone only, (8.1 months).7 Nearly all patients given pomalidomide in the MM-003 study showed improved quality of life.[2] The most commonly reported Grade 3 or 4 adverse reactions included neutropenia, thrombocytopenia and infections.[7]
About pomalidomide
Pomalidomide is an oral immunomodulatory drug (IMiD®) with a multimodal mechanism of action consisting of three main effects: direct antimyeloma, stromal inhibitory effects and immunomodulatory effects. Pomalidomide has been approved for adult patients who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on the last therapy.[6]
The recommended starting dose of pomalidomide will be 4 mg once daily, orally on days 1-21 of repeated 28-day cycles until disease progression. Pomalidomide should be given with low dose dexamethasone.
About the MM-003 study
The European Commission's decision was based on the results of the MM-003 study, a Phase III, multi-centre, randomised (2:1), open-label study in 455 patients.
The trial evaluated use of oral pomalidomide plus low-dose dexamethasone (n=302) compared with high-dose dexamethasone (n=153) in patients with rrMM. According to the protocol, all patients were to have been treated with both bortezomib and lenalidomide prior to study entry. In the trial, progression-free survival, the primary endpoint, was significantly longer in patients who received pomalidomide plus low-dose dexamethasone (3.6 months) compared with those who received high-dose dexamethasone alone (1.8 months [HR, 0.45; P<0.001]). Median overall survival, the secondary endpoint, was also significantly improved for pomalidomide plus low-dose dexamethasone arm (12.7 months), compared with high-dose dexamethasone only (8.1 months) (due to patients still on therapy in the pomalidomide plus low-dose dexamethasone arm, the median has not yet been reached vs. 34 weeks in the high-dose dexamethasone arm [HR, 0.53; P<0.001]).[7]