The approval was based on results from a multicenter, open-label phase 2b study in which the overall response rate with Evomela was 95 percent among 61 patients.
The FDA has approved Evomela (Captisol-enabled melphalan) as a high-dose conditioning treatment for use in patients with multiple myeloma prior to autologous stem cell transplantation (ASCT), as well as for the palliative treatment of patients with myeloma for whom oral therapy is not appropriate. Spectrum Pharmaceteucials, the developer of the drug, announced the approval on March 15.
The approval was based on results from a multicenter, open-label phase 2b study in which the overall response rate (ORR) with Evomela was 95 percent among 61 patients, with all patients having successful myeloablation (median five days post-ASCT) and subsequent neutrophil and platelet engraftment (median of 12 to 13 days post-ASCT) with no mortality at day 100.
“The approval of Evomela marks the first new formulation of melphalan approved by the FDA, since its initial approval in 1964,” according to a statement from lead author Parameswaran Hari, Armand J. Quick/William F. Stapp Professor of Hematology at the Medical College of Wisconsin, director of the Adult Blood and Marrow Transplant Program at Froedtert Hospital and the section head of Hematologic Malignancies and Transplantation, in the Division of Hematology and Oncology in the Department of Medicine.
“[Evomela] is extensively used in the treatment of multiple myeloma and is the main drug in conditioning therapy pretransplant. Evomela’s new formulation does not contain propylene glycol and is stable for four hours at room temperature in addition to the one hour following reconstitution.”
The phase 2 trial included 56 newly diagnosed multiple myeloma patients and five patients who had relapsed following ASCT. Patients had received a median of three prior lines of therapy (ranging from two to 16). The trial’s primary endpoint was safety, with secondary endpoints focused on efficacy and rates of myeloablation and engraftment.
Patients received 200 mg/m2 of [Evomela] followed by ASCT. The treatments were administered in 100 mg/m2 doses 3 and two days prior to transplantation. Investigator-assessed ORR was 95 percent, with a complete response (CR) rate of 31 percent (16 percent stringent CRs). ORR and CR rates were 100 percent and 21 percent, respectively, by independent pathology review. According to Spectrum, the lower CR rate by independent review could be attributed to missing data.
The most common grade 3/4 adverse events were hematologic in nature, including neutropenia, leukopenia, lymphopenia, thrombocytopenia and anemia.
The most frequently reported grade 3/4 nonhematologic adverse events were hypophosphatemia (48 percent), hypokalemia (28 percent), febrile neutropenia (28 percent), mucosal inflammation (10 percent) and stomatitis (5 percent). The most common all-grade nonhematologic toxicities were diarrhea (93 percent), nausea (90 percent), fatigue (77 percent), hypokalemia (74 percent) and vomiting (64 percent).
Spectrum gained development and commercialization rights to [Evomela] from Ligand Pharmaceuticals Incorporated in March 2013.
“I am very proud to announce that Spectrum has been able to bring another new cancer drug to the market,” Rajesh C. Shrotriya, chairman and CEO of Spectrum Pharmaceuticals said in a statement. “This represents the commercialization of our sixth Hematology/Oncology product in the United States. Our Evomela formulation does not contain propylene glycol and is reconstituted and admixed with normal saline. This new formulation also uses Captisol technology, which allows the admixture solution to be stable for 4 hours at room temperature in addition to the one hour following reconstitution and has been used in several other FDA-approved products.”
Hari PN, Ajitawi O, Arce-Lara C, et al. Results of a phase ii study of propylene glycol (PG)-free, captisol-enabled melphalan conditioning for autologous hematopoietic stem cell transplantation (AHCT) in patients with multiple myeloma (MM). BBMT. 2015;21(2)(suppl):S138.