YM BioSciences Inc. (NYSE Amex: YMI, TSX:YM), announced the conclusion of dose-escalation in the Phase I portion of its Phase I/II clinical trial of CYT387 at Mayo Clinic in patients with myelofibrosis. In total, 21 patients were treated in Phase I, with no voluntary withdrawals reported. CYT387 has shown significant activity in reducing spleen size and controlling constitutional symptoms in these patients. To date, 15 patients have been enrolled into the Phase II portion of the study. Given the favourable biological activity and safety data, the Company intends to expand the present program from 60 to 120 patients at up to six centers in the United States, Canada and Australia, subject to regulatory approval. Detailed safety and activity data for CYT387 are planned to be presented at the American Society of Hematology (ASH) meeting in Orlando, Florida in December this year.
Myelofibrosis is a chronic debilitating unmet medical need, in which a patient's bone marrow is replaced by scar tissue and for which treatment options are limited or unsatisfactory due to both efficacy and safety concerns.
Dosing in the Phase I dose-escalation portion of the study commenced in November 2009. In total, 21 patients were treated across five dosing levels (100, 150, 200, 300 and 400mg daily for up to nine months). Reversible, dose-limiting toxicities (DLTs) were observed in two patients at the 400mg dose-level, namely an asymptomatic Grade 3 amylase and lipase elevation and a Grade 3 headache with both patients subsequently resuming treatment with CYT387 at reduced doses.
The majority of patients experienced a rapid splenic response of a magnitude sufficient to encourage YM to increase the total number of 60 patients previously targeted to a maximum of 120 patients (subject to regulatory approval). This further expansion of the trial will allow exploration of the dose-dependency of the biological activity observed in the Phase I portion of the study. The expansion will also facilitate the collection of more safety and efficacy data at the two doses of interest (150 and 300mg) whilst also allowing detailed analysis of particular patient subsets.
Whereas the initial protocol measured spleen size reduction by palpation, MRI is proposed to be included in the expanded protocol to augment the clinical data set.
"We have continued to see very favorable biological activity data for CYT387, with disease-modifying effects comparable to other JAK2 inhibitors evident in my myelofibrosis patients, including significant spleen size reduction, improvement in constitutional symptoms and favorable hematological changes. The lack of patient withdrawal from the study is also testament to the tolerability and patient acceptability of this drug," said Dr. Ayalew Tefferi, Professor of Hematology at Mayo Graduate School and Chair of the study.
"We continue to be compelled by the early observations of activity and tolerability for CYT387," said Dr. Nick Glover, COO of YM BioSciences. "The Company remains on track to advance CYT387 towards an NDA-enabling study as early as 2011 and is reviewing opportunities for the compound in the numerous other indications in which evidence of activity has been shown with this family of molecules."
"This important deployment of resources to the JAK inhibitor program requires that we evaluate the allocation of our existing capital," said David Allan, Chairman and CEO, "As a consequence, we have decided to terminate further expenditures on the AeroLEF program at this time. We believe that CYT387 has the potential to be a competitive molecule across a spectrum of disorders, including indications in hematology, oncology and inflammatory diseases. As such, we are allocating our resources accordingly in order to maximize its preclinical and clinical development in the near term."