2007.12.12 – Phase I data for myelofibrosis drug

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Exelixis presents encouraging Phase I data for myelofibrosis drug

12th December 2007
By Staff Writer

Exelixis has reported positive data from an ongoing Phase I trial of XL019 in patients with myelofibrosis, a myeloproliferative disorder.

XL019 is an investigational small molecule that selectively inhibits the tyrosine kinase JAK2, one of four JAK family members activated in response to cytokines and hematopoietic growth factors.

The Phase I dose escalation study of XL019 is ongoing in subjects with primary myelofibrosis (MF) and post-polycythemia vera/essential thrombocythemia MF. To date nine patients have been enrolled. The primary objective of this study is to determine the safety and tolerability of XL019 when administered orally once daily for 21 days in 28-day cycles. Secondary objectives include evaluation of the pharmacokinetics and pharmacodynamics of XL019, and to evaluate response using the International Working Group for MF consensus response criteria.

Presented unaudited data from cohort 1 (100mg), cohort 2 (200mg) and cohort 3 (300mg) showed reduction in spleen size of 33% to 100% in five of six patients evaluated. Reduction in erythropoietin-independent colony formation of up to 39% and up to 100% was observed in two patients evaluated.

Data also showed relief of constitutional symptoms, including pruritus, fatigue, back pain and abdominal fullness and reduction in the number of cells with the JAK2 V617F mutation (allele burden). XL019 was generally well tolerated. Adverse events included Grade 1 nausea, headaches, equilibrium imbalance, dizziness, chest discomfort, visual disturbances, fatigue and hypertension.