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The US Food and Drug Administration (FDA) has said that, at present, it cannot approve a propylene glycol-free melphalan formulation (Evomela) for use in patients with multiple myeloma (MM).
Spectrum Pharmaceuticals is seeking approval for Evomela as a high-dose conditioning treatment for MM patients undergoing hematopoietic stem cell transplant (HSCT) and for palliative treatment in MM patients for whom oral therapy is not appropriate.
The FDA issued a Complete Response Letter stating that the new drug application (NDA) for Evomela cannot be approved in its present form.
However, the FDA did not identify any clinical deficiency in the NDA package.
“We will work swiftly with the FDA to address the Complete Response Letter,” said Rajesh C. Shrotriya, MD, chairman and chief executive officer of Spectrum Pharmaceuticals. “We remain committed to bringing Evomela to the market for patients and plan to work closely with the FDA.”
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time to 5 hours. This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013. Spectrum assumed responsibility for completing the pivotal phase 2 clinical trial and was responsible for filing the NDA. Spectrum filed the NDA in December 2014, and the FDA accepted the application the following March.
The FDA has granted Evomela orphan drug designation for use as a high-dose conditioning regimen for MM patients undergoing HSCT.
Phase 2 study
Researchers have evaluated Evomela in a phase 2, multicenter trial. Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation last month.
The latest publication includes data on 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT. The patients received Evomela at 200 mg/m2 given as 2 doses on Day -3 and Day -2 prior to HSCT (Day 0).
Efficacy was assessed by clinical response at Day +100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
All 5 patients who had previously relapsed from a prior HSCT responded to Evomela.
All patients in the study achieved myeloablation with a median of 5 days post-HSCT. All patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified. 
Photo by Chad McNeeley
The US Food and Drug Administration (FDA) has said that, at present, it cannot approve a propylene glycol-free melphalan formulation (Evomela) for use in patients with multiple myeloma (MM).
Spectrum Pharmaceuticals is seeking approval for Evomela as a high-dose conditioning treatment for MM patients undergoing hematopoietic stem cell transplant (HSCT) and for palliative treatment in MM patients for whom oral therapy is not appropriate.
The FDA issued a Complete Response Letter stating that the new drug application (NDA) for Evomela cannot be approved in its present form.
However, the FDA did not identify any clinical deficiency in the NDA package.
“We will work swiftly with the FDA to address the Complete Response Letter,” said Rajesh C. Shrotriya, MD, chairman and chief executive officer of Spectrum Pharmaceuticals. “We remain committed to bringing Evomela to the market for patients and plan to work closely with the FDA.”
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time to 5 hours. This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013. Spectrum assumed responsibility for completing the pivotal phase 2 clinical trial and was responsible for filing the NDA. Spectrum filed the NDA in December 2014, and the FDA accepted the application the following March.
The FDA has granted Evomela orphan drug designation for use as a high-dose conditioning regimen for MM patients undergoing HSCT.
Phase 2 study
Researchers have evaluated Evomela in a phase 2, multicenter trial. Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation last month.
The latest publication includes data on 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT. The patients received Evomela at 200 mg/m2 given as 2 doses on Day -3 and Day -2 prior to HSCT (Day 0).
Efficacy was assessed by clinical response at Day +100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
All 5 patients who had previously relapsed from a prior HSCT responded to Evomela.
All patients in the study achieved myeloablation with a median of 5 days post-HSCT. All patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.
Photo by Chad McNeeley
The US Food and Drug Administration (FDA) has said that, at present, it cannot approve a propylene glycol-free melphalan formulation (Evomela) for use in patients with multiple myeloma (MM).
Spectrum Pharmaceuticals is seeking approval for Evomela as a high-dose conditioning treatment for MM patients undergoing hematopoietic stem cell transplant (HSCT) and for palliative treatment in MM patients for whom oral therapy is not appropriate.
The FDA issued a Complete Response Letter stating that the new drug application (NDA) for Evomela cannot be approved in its present form.
However, the FDA did not identify any clinical deficiency in the NDA package.
“We will work swiftly with the FDA to address the Complete Response Letter,” said Rajesh C. Shrotriya, MD, chairman and chief executive officer of Spectrum Pharmaceuticals. “We remain committed to bringing Evomela to the market for patients and plan to work closely with the FDA.”
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time to 5 hours. This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013. Spectrum assumed responsibility for completing the pivotal phase 2 clinical trial and was responsible for filing the NDA. Spectrum filed the NDA in December 2014, and the FDA accepted the application the following March.
The FDA has granted Evomela orphan drug designation for use as a high-dose conditioning regimen for MM patients undergoing HSCT.
Phase 2 study
Researchers have evaluated Evomela in a phase 2, multicenter trial. Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation last month.
The latest publication includes data on 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT. The patients received Evomela at 200 mg/m2 given as 2 doses on Day -3 and Day -2 prior to HSCT (Day 0).
Efficacy was assessed by clinical response at Day +100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
All 5 patients who had previously relapsed from a prior HSCT responded to Evomela.
All patients in the study achieved myeloablation with a median of 5 days post-HSCT. All patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.