Fedratinib exposure–response in MF: Pooled phase II/III data

Exposure–response analyses of pooled data from phase II/III studies evaluating fedratinib in  patients with intermediate-2 or high-risk myelofibrosis (MF; N = 430) were recently published in the British Journal of Clinical Pharmacology by Chen et al.

Key data: Fedratinib exposure was positively associated with spleen volume reduction ≥35% (SVR35) (odds ratio [OR], 38.2; 95% confidence interval [CI], 12.4–118; p < 0.001) and total symptom score reduction ≥50% (TSS response) (OR, 20.8; 95% CI, 6.27–69.2; p < 0.001). Prior ruxolitinib exposure was not associated with SVR35 (p = 0.090) or TSS response (p = 0.326). Although numerically higher adverse event (AE) incidence was observed with higher fedratinib exposure, there was no significant association between fedratinib exposure and safety endpoints. 

Key learning: Across phase II/III studies, higher fedratinib exposure was positively associated with efficacy of fedratinib in patients with MF. Fedratinib 400 mg once daily is an appropriate dose for patients with MF, regardless of ruxolitinib exposure.