On March 9, 2015 Spectrum Pharmaceuticals reported that its New Drug Application (NDA) for Captisol-Enabled Melphalan (CE-Melphalan), has been accepted by the U.S. Food and Drug Administration (FDA) (Press release, Spectrum Pharmaceuticals, MAR 9, 2015, View Source [SID:1234502226]). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of October 23, 2015 for the CE-Melphalan NDA, which is 10 months from the filing date. Spectrum is seeking FDA approval for its use as a high-dose conditioning treatment prior to autologous hematopoietic (progenitor) stem cell transplantation (AHCT) in patients with multiple myeloma (MM), an orphan drug designation. Spectrum is also seeking approval for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

“We are excited the CE-Melphalan filing has been accepted by the FDA, representing another important company milestone,” said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. “CE-Melphalan met all pivotal trial endpoints, and we expect to launch this drug if approved, using our existing sales force towards the end of the year. The drug’s improved solubility and stability should make it an attractive treatment option for both transplant conditioning and the palliative treatment of patients with MM. Eliminating the need for propylene glycol in the preparation of CE-Melphalan eliminates the risk of the toxicities associated with this excipient. In addition, CE-Melphalan’s increased stability simplifies the logistics for pharmacies and nursing staff, and is anticipated to allow for longer infusion times which may permit the administration of higher dose intensities. We anticipate these characteristics of CE-Melphalan will facilitate rapid adoption. We look forward to bringing this drug to market and providing additional treatment options to patients suffering with cancer.”

The Phase 2 pivotal trial evaluating CE-Melphalan was a multi-center trial evaluating safety and efficacy. The primary objective of the study was to determine the overall safety and toxicity profile in MM patients receiving 200 mg/m2 of CE-Melphalan as myeloablative therapy prior to AHCT. The secondary objectives evaluated the efficacy of CE-Melphalan in this patient population as measured by Multiple Myeloma Response Rate (according to International Myeloma Working Group [IMWG] criteria), and the rates of myeloablation and engraftment. Study results support the safety and efficacy of high-dose CE-Melphalan as a high-dose conditioning treatment prior to AHCT in patients with MM. CE-Melphalan led to successful myeloablation and subsequent engraftment in all (100%) of the MM patients studied with no mortality or unexpected transplant-related toxicity. Overall, 95% of subjects (n=61) responded to high dose CE-Melphalan, and 67% VGPR or better responses were achieved in the subgroup of high risk patients (15%). There were no deaths by Day 100, and the most common Grade 3 and 4 toxicities were the expected hematologic events (neutropenia, leukopenia, lymphopenia, thrombocytopenia and anemia). The most frequent non-hematologic adverse events included diarrhea, nausea, and fatigue. Importantly, the incidence of severe mucositis was low (Grade 3/4; 10%).

Spectrum Pharmaceuticals gained global development and commercialization rights to CE-Melphalan from Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) in March 2013. Spectrum assumed the responsibility for the pivotal clinical trial and was responsible for filing the NDA. Under the license agreement, Ligand received a license fee and is eligible to receive milestone payments, as well as royalties following potential commercialization.