Æterna Zentaris Inc, a late-stage drug development company specialized in oncology and endocrine therapy, has requested Scientific Advice from the European Medicines Agency (EMA) to assure the acceptability of the recently initiated phase-3 programmes for the development of its lead anticancer compound, perifosine, in its two lead indications, multiple myeloma and refractory advanced colorectal cancer. Previously, agreement was reached with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the pivotal studies in each of the lead indications, which will be sponsored by Keryx Biopharmaceuticals Inc., (Keryx), Æterna Zentaris’s licensee for perifosine in North America.
In multiple myeloma, the SPA-agreed upon phase-3 study is a double-blind, placebo-controlled study of perifosine combined with bortezomib (Velcade) in bortezomib pretreated patients. Progression-free survival will be the primary efficacy endpoint in this trial, which will include follow-up for overall survival. The advice from the EMA indicates that, in principle, the proposed study is considered sufficient to provide all data necessary to support a marketing authorization of perifosine in combination with bortezomib (Velcade). At the relevant time, the actual approved indication in Europe will have to take into account the availability of liposomal doxorubicin (Caelyx), which in the European Union is approved in bortezomib pretreated patients with multiple myeloma. Further, the EMA has confirmed that the planned electrocardiogram (ECG) evaluations included in the phase-3 study will suffice to assess the cardiac safety of perifosine. Therefore, the Company does not intend to initiate any additional study with perifosine in Europe for the multiple myeloma indication.
Æterna Zentaris has also requested Scientific Advice for the development of perifosine in refractory advanced colorectal cancer, where the SPA-agreed upon phase-3 study is a double-blind placebo-controlled study comparing the combination of perifosine and capecitabine (Xeloda) with single-agent capecitabine (Xeloda). Patients in this study will be intensively pretreated and will have failed all available treatment options except capecitabine (Xeloda). Overall survival will be analyzed as the primary efficacy endpoint. For both indications, safety data from studies of perifosine in other indications and drug combinations will be used as supportive information to define the clinical safety profile of perifosine.
Dr Juergen Engel, president and CEO of Æterna Zentaris stated, "We are very pleased with the outcome of our discussions with the European Medicines Agency so far. For the development of perifosine in multiple myeloma, we believe that the planned North American clinical program, which is sponsored by our partner Keryx, is sufficient to support an application for marketing authorization in Europe and the rest of the world. We are looking forward to the outcome of our discussions with the EMA which is expected during the third quarter of this year, regarding our development program in colorectal cancer."
Scientific Advice is a procedure offered by the European Medicines Agency to stakeholders for clarification of questions arising during development of medicinal products.
Perifosine is a novel, potentially first-in-class, oral anticancer agent that modulates Akt, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, all of which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival.
Æterna Zentaris Inc. is a late-stage drug development company specialized in oncology and endocrine therapy.