An early proof-of-concept study presented shows promising results for imatinib in the treatment of pulmonary arterial hypertension (PAH), a severe, incurable blood vessel disorder.

Preliminary findings from a 59-patient, multi-center phase-II clinical trial suggest imatinib provides a treatment benefit, as demonstrated by a significant improvement in pulmonary vascular resistance and a numerical increase in cardiac output, key hemodynamic measures used to monitor the progression of the disease. Improvements in the six-minute walk test, the primary endpoint of the study, approached, but did not reach, statistical significance.

These initial data were presented today at the European Respiratory Society (ERS) congress in Berlin, Germany, and further details on the study are expected to be published later this year. Imatinib is available for oncology indications in many countries as Glivec (imatinib), and as Gleevec (imatinib mesylate) tablets in the US, Canada and Israel.

"The outcomes of this trial are clinically important given the rapid progression of PAH and the poor prognosis for these patients," said Professor Ardeschir Ghofrani, head of Pulmonary Hypertension Division, University Hospital Giessen und Marburg, Germany. "Our observations suggest that imatinib holds promise in treating PAH."

PAH is a debilitating disease that is characterized by a marked and sustained elevation in pulmonary artery pressure. The disease is rapidly progressive and can result in heart failure and death. There is no known cure for PAH and the goal of current treatments is to control symptoms of the disease. The prognosis for many PAH patients are similar to that of some advanced cancers, and with current treatment options, the five-year survival rate is 50 per cent.

Imatinib is an orally administered targeted therapy that has successfully treated many patients with certain rare cancers. It works by inhibiting the activity of several proteins called tyrosine kinases, such as Bcr-Abl, c-KIT and platelet-derived growth factor receptor (PDGFR), which is also thought to be involved in the progression of PAH. In patients with PAH, PDGFR may cause smooth muscle cells in the pulmonary arteries to multiply, resulting in the constriction of these arteries.

Plans for research to further explore the potential of imatinib in PAH are ongoing and will be announced at a later date.

The double blind, placebo-controlled trial presented at ERS enrolled 59 patients with PAH to evaluate the effectiveness and safety of imatinib 400 mg. The study participants had previously failed to improve after receiving standard therapy with prostanoids, endothelin antagonists or PDE-5 inhibitors.

"There is a high unmet need for new treatments that address the underlying mechanisms of PAH," said David Epstein, president and CEO of Novartis Oncology. "These early findings support exploring the potential of imatinib in PAH in a larger randomized clinical trial."

It is estimated that approximately 130,000 to 260,000 people worldwide have PAH. The mean age at diagnosis is 35 years, and most patients present with moderate-to-severe disease. PAH occurs most often in otherwise healthy people, and more often in women than in men.

The exact process by which PAH develops is not known. However, it appears to be associated with a variety of disease processes, including chronic thromboembolic disease (blood clots), connective tissue diseases, congenital heart disease and exposure to external factors including appetite suppressants or infectious diseases such as HIV.

Novartis has also conducted early stage research with imatinib in another non-oncology disease called idiopathic pulmonary fibrosis (IPF), a condition in which the lungs become scarred over time, making it more and more difficult to breathe. Early clinical trial results in IPF did not show a significant treatment benefit over placebo, and clinical trials have therefore been halted.

Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML.