FDA Approves Evomela for Two Multiple Myeloma Indications


March 16, 2016

The US Food and Drug Administration (FDA) has granted approval for Captisol-enabled melphalan (Evomela, Spectrum) for two indications in multiple myeloma.

One indication is for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation (HSCT) for patients with multiple myeloma, and the second is as palliative treatment for myeloma patients who are not candidates for oral therapy.

This is the first drug to gain FDA approval for the high-dose conditioning indication in multiple myeloma.

"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, who is the Armand J. Quick/William F. Stapp Professor of Hematology at the Medical College of Wisconsin in Milwaukee, and lead author of the study that led to the drug's approval.

"Melphalan is extensively used in the treatment of multiple myeloma and is the main drug in conditioning therapy pretransplant," Dr Hari said in a statement.

Evomela is a new formulation of melphalan that is free of propylene glycol. According to the manufacturer, the use of Captisol, a specially modified cyclodextrin, improves the solubility and stability of melphalan, and thus eliminates the need for propylene glycol, which can cause complications such as metabolic/renal dysfunction and arrhythmias.

Approval was granted on the basis of results from a multicenter, open-label, phase 2b study of 61 patients — five who had relapsed prior to HSCT and 56 with newly diagnosed disease (Biol Blood Marrow Transplant. 2015;21:2100-2105)

Patients received 200 mg/m² of Evomela, administered in 100 mg/m² doses on day 3 and day 2 before transplantation.

Efficacy was assessed by clinical response at day +100. There was an overall response rate of 95% and a complete response (CR) rate of 31% (16% stringent CRs), as determined by investigator assessment.

The overall response rate was 100% and the CR rate was 21% on independent pathology review. According to the manufacturer, the lower rate of confirmed CRs in the independent review was related to missing data.

Of note, the five patients who had relapsed after a previous HSCT all showed a response to Evomela.

All study participants achieved myeloablation a median of 5 days after HSCT, all had successful neutrophil a median of 12 days after HSCT, and all had platelet engraftment a median of 13 days after HSCT.

There was no treatment-related mortality, and nonhematologic adverse events were mostly grade 1 and grade 2.

The incidence of grade 3 mucositis was 10%, of grade 3 stomatitis was 5%, and of treatment-emergent serious adverse events, most of which were grade 3, was 20%. These events are commonly reported in patients undergoing myeloablative chemotherapy, and no new safety signals were identified, according to the company.

The FDA declined to approve Evomela last October, but their Complete Response Letter did not identify any clinical deficiency in Spectrum's New Drug Application package.

Spectrum gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals in March 2013.


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