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Spectrum Pharmaceuticals
The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.
The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.
Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).
This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
The full prescribing information for Evomela is available at www.evomela.com.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.
Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.
Phase 2 study
Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.
Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.
Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.
The patients received Evomela at 200 mg/m2, given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).
All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.
