Genzyme Corp. announced that its second phase III trial of Mozobil (plerixafor) has successfully met its primary and secondary endpoints, demonstrating positive results in multiple myeloma (MM) similar to those reported two weeks ago in non-Hodgkin's lymphoma.
The combined strength of these two trials in which patients with two types of cancer achieved more rapid and effective mobilization of stem cells in preparation for transplant than patients treated with current therapies will support Mozobil's regulatory approval, commercialisation, and likely adoption as a standard of care in transplantation.
The randomised, double-blind, placebo-controlled trial included 302 patients who were undergoing a haematopoietic stem cell transplant (HSCT) for multiple myeloma at medical centres in the United States, Canada, and Europe. Like the previous trial, it examined the effectiveness of Mozobil in increasing the number of haematopoietic stem cells collected for a transplant, comparing the stem cell yield from patients treated with Mozobil following G-CSF to patients treated with placebo following G-CSF.
In the primary efficacy endpoint, 72 per cent of patients treated with Mozobil and G-CSF achieved the target threshold for collection of at least 6 million CD34+cells/kg from the peripheral blood with two days or fewer of apheresis sessions, compared with 34 percent of patients in the G-CSF/placebo group. This two-fold increase was statistically significant in favour of the Mozobil-treated patients. Like the previous trial, these results exceed the 20 per cent absolute difference prospectively defined through the FDA's Special Protocol Assessment as a successful result.
The median number of days to achieve the target of six million cells was one day for the Mozobil/G-CSF group and four days for the G-CSF/placebo group. Over half of patients treated with Mozobil and G-CSF reached the target cells in the first day of apheresis. By comparison, it took four days for a similar percentage of the G-CSF/placebo group to reach this threshold.
Secondary outcomes were consistent with the primary endpoint, showing a statistically significant result in favour of Mozobil in the number of patients who reached the target threshold of at least six million CD34+cells/kg from the peripheral blood with four days of apheresis, and the number of patients who reached at least two million cells collected in four days.
Other secondary outcomes were also supportive, including the success of engraftment, the number of days needed to engraft, and the durability of the engraftment for the first 100 days. The trial also robustly met the primary endpoint specified by the European Agency for the Evaluation of Medicinal Products (EMEA) - a composite of successful mobilization and engraftment.
Mozobil was well tolerated in the trial, with the most common adverse events being mild gastrointestinal effects and redness at the site of injection. The only serious adverse event deemed related to treatment occurred in the G-CSF/placebo group.
"Taken together, these two pivotal trials paint a dramatic picture of the role that Mozobil will play in the treatment of patients with lymphoma and multiple myeloma," said Henri A. Termeer, chairman and chief executive officer, Genzyme. "Mozobil has shown the ability to quickly and predictably prepare a patient for a transplant, providing a strong clinical and economic argument in favour of its use in all autologous transplant procedures. We will work aggressively to gain regulatory approval in these transplant settings, while also pressing forward to unlock the full potential of Mozobil in allogeneic transplantation, chemosensitization, cardiovascular disease, and other promising applications."