The Food and Drug Administration (FDA) has approved Spectrum Pharmaceutical’s Evomela (Captisol-enabled melphalan HCl) for Injection 50mg (free base)/vial for the treatment of patients with multiple myeloma. Specifically, the drug was approved for the following indications:
- High-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma
- Palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate
In October 2015, Spectrum received a Complete Response Letter (CRL) from the FDA indicating that the application in its current form could not be approved, although the FDA did not indicate any clinical deficiency in the CRL. The company provided an amended application to the FDA on November 7th, 2015 which was then reviewed by the FDA and accepted for approval.
Evomela, a propylene glycol-free melphalan formulation, was granted Orphan Drug Designation for its use as a high-dose conditioning regimen for patients with multiple myeloma undergoing autologous stem cell transplant. The formulation eliminates the need to use a propylene glycol containing custom diluent (required with other melphalan formulations) which has been linked to renal and cardiac side effects.
Evomela utilizes Captisol technology, a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. The use of Captisol to reformulate melphalan improved its stability, extending it use time to 5 hours, allowing for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
Melphalan is an alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells.
For more information visit FDA.gov.