SAN DIEGO — Imatinib may have a future as a treatment for pulmonary arterial hypertension.
The oral tyrosine kinase inhibitor significantly improved exercise capacity in a phase II study, as reflected in increased 6-minute walk distance in a patient subgroup with a baseline pulmonary vascular resistance (PVR) of at least 1,000 dyne*sec/cm
Additional benefits seen with imatinib (Gleevec)—again restricted to patients having PVR elevated above the 1,000-dyne threshold—included significantly increased cardiac output, reduced mean pulmonary arterial pressure, and decreased PVR, Dr. Robyn Barst reported at the annual meeting of the American College of Chest Physicians.
Those findings in a post hoc analysis of the phase II data provided the impetus for the ongoing phase III IMPRES (Imatinib in Pulmonary Arterial Hypertension, a Randomized Efficacy Study).
IMPRES is a 24-week, double-blind clinical trial evaluating the safety and efficacy of the tyrosine kinase inhibitor as add-on therapy in 200 patients with pulmonary arterial hypertension (PAH) who are in functional class II-IV and remain symptomatic on two or more PAH therapies. Participants, all of whom had a baseline PVR of at least 1,000 dyne*sec/cm
The phase II study involved 59 patients with PAH. Overall, the primary end point of that study (the mean change in 6-minute walk distance during 24 weeks) was not significantly different between the imatinib and placebo groups.
However, roughly half of the subjects in the phase II study had a baseline PVR of 1,000 dyne*sec/cm
In addition, mean pulmonary arterial pressure improved by a mean 8.4 mm Hg in the imatinib group, which was significantly better than the mean 2.8–mm Hg reduction with placebo. Cardiac output increased by a mean 1.3 L/min from a baseline value of 3.0 L/min with imatinib, compared with a 0.2-L/min gain with placebo. PVR dropped by a mean 576 dyne*sec/cm
Imatinib is approved for the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and several other malignancies. The rationale for developing the drug as a possible treatment for PAH lies in imatinib's ability to inhibit platelet-derived growth factor receptor alpha and beta kinases. Platelet-derived growth factor and its receptor have been implicated in the pathogenesis of PAH, a progressive disorder with a poor prognosis for which no cure exists, she noted.
Disclosures: Both the phase II study and IMPRES were funded by Novartis. Dr. Barst disclosed serving as a consultant to Novartis and several other pharmaceutical companies.