FDA Approves Propylene Glycol–Free Melphalan Formulation

March 28, 2016

The FDA has approved two indications of a new formulation of melphalan hydrochloride called Evomela for the treatment of multiple myeloma.

The US Food and Drug Administration (FDA) has approved two indications of a new formulation of melphalan hydrochloride called Evomela for the treatment of multiple myeloma. The drug has been approved for use as a high-dose conditioning treatment given before patients undergo autologous stem cell transplantation, and for use as a palliative treatment in patients with myeloma who cannot be treated with oral therapy.

According to a press release by the drug’s manufacturer, Evomela is the first product to be approved by the FDA for high-dose conditioning in multiple myeloma. This new formulation of melphalan does not contain propylene glycol. In contrast, current formulations of melphalan require the use of propylene glycol as a cosolvent, which has been associated with adverse effects such as metabolic dysfunction and arrhythmias.

Evomela’s use of Captisol technology to reformulate contributes to the 4-hour admixture stability of Evomela at room temperature, in addition to the 1-hour stability of reconstituted Evomela at room temperature and the 24-hour stability at refrigerated temperature.

“The approval of Evomela marks the first new formulation of melphalan approved by the FDA, since its initial approval in 1964,” said Parameswaran Hari, MD, of the division of hematology and oncology at the Medical College of Wisconsin in Milwaukee, in a press release. “Melphalan is extensively used in the treatment of multiple myeloma and is the main drug in conditioning therapy pre-transplant.”

The FDA granted this approval for high-dose conditioning based on the results of a phase II clinical trial published in 2015 in Biology of Blood and Marrow Transplantation. In the trial, 61 patients with myeloma were given 2 doses of Evomela at 100 mg/m2. Fifty-six patients had newly diagnosed disease and five patients had relapsed after stem cell transplant.

After undergoing transplant, all patients achieved myeloablation (median time of 5 days). All patients also achieved neutrophil and platelet engraftment. The overall response rate to the drug was 100%, with 21% of patients achieving an overall complete response and 79% of patients achieving an overall partial response. There was no mortality at 100 days.

No grade 4 mucositis or stomatitis occurred; 10% of patients had grade 3 mucositis and 5% had grade 3 stomatitis.