Plerixafor: AMD 3100, AMD3100, JM 3100, SDZ SID 791

Plerixafor [Mozobil, AMD 3100, JM 3100, SDZ SID 791] is a bicyclam derivative that acts as a stem cell mobiliser by blocking the CXCR4 chemokine receptor. Plerixafor was synthesised by Johnson Matthey (AnorMED) in collaboration with the Rega Institute of Leuven, Belgium. Plerixafor is in phase III clinical trials in stem cell transplantation among cancer patients. Plerixafor blocks CXCR4, which triggers the rapid movement of stem cells out of the bone marrow and into circulating blood. These cells can then be collected and used in stem cell transplant procedures. Plerixafor had been available for partnering in Europe. However, decisions concerning partnering arrangements were deferred by AnorMED until top-line clinical data became available (expected in 2007). In November 2006, Genzyme Corporation completed its acquisition of AnorMED. Genzyme intends to commercialise plerixafor in >50 countries throughout the world using its existing transplant business. Evotec OAI was selected by AnorMED to support it in the chemical development of plerixafor. Evotec OAI will use EVOdevelop, its integrated chemical and pharmaceutical development platform, to complete the full validation of the process to plerixafor, including process research and development, cGMP manufacturing and analytical work. Evotec OAI will also be responsible for producing the relevant Chemical Manufacturing Control (CMC) documentation for regulatory filings. Top line results from the phase III studies are expected in the second quarter of 2007 and, assuming these are successful, the marketing submissions are planned for the US in 2007 (launch in 2008), and for Canada and Europe in 2008. Plerixafor has orphan drug status for stem cell transplantation in cancer patients in the US and the EU. AnorMED (now Genzyme) decided to pursue a full Marketing Authorisation Application (MAA) in Europe for plerixafor in stem cell transplant. Previously, the company had been planning on filing a CMA (Conditional Marketing Authorisation) in this region. The change in strategy requires additional phase II trials in the five major EU markets. Multicentre phase II trials with plerixafor have begun in Canada and Germany in approximately 50 patients with non-Hodgkin's lymphoma and multiple myeloma (studies EU21 and C201). Enrolment has been completed in a US-based, multicentre, phase II trial (study 2105) of plerixafor plus G-CSF in patients with multiple myeloma and non-Hodgkin's lymphoma. This study is designed to optimise the administration schedule of this combination therapy regimen. Plerixafor has completed a phase II study (study 2104) in multiple myeloma and NHL patients in combination with chemotherapy. A US-based phase II pilot study (study 2108) with plerixafor as a single mobilising agent in multiple myeloma patients undergoing stem cell transplant is underway. Another US-based phase II pilot study (study 2106) is evaluating plerixafor in combination with the standard mobilisation regimen, G-CSF, in patients with Hodgkin's disease undergoing stem cell transplant. AnorMED completed a phase II study (study 2101) evaluating the potential of plerixafor in combination with G-CSF as a therapy for stem cell transplantation compared to G-CSF therapy alone. The study involved patients with multiple myeloma and patients with NHL. Results indicated that the combination regimen was significantly superior to G-CSF treatment alone in stem cell mobilisation. Further trials are planned for plerixafor, to expand its use in transplant and in other indications including one to investigate the potential of plerixafor to improve the effectiveness of chemotherapy in patients with leukaemia. Phase I trials have been completed.