An early
proof-of-concept study presented shows promising results for imatinib
mesylate 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 mesylate 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 mesylate is
available for oncology indications as Gleevec(R) in the US, Canada and
Israel and as Glivec(R) (imatinib), in countries outside of 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, MD, Head of Pulmonary Hypertension Division,
Buy generic clomid University Hospital Giessen und Marburg, Germany. "Our observations suggest
that imatinib mesylate holds promise in treating PAH."
PAH is a debilitating disease that is characterized by a marked and
sustained elevation in pulmonary artery pressure(1). The disease is rapidly
progressive and can result in heart failure and death(1). There is no known
cure for PAH and the goal of current treatments is to control symptoms of
the disease(2). The prognosis for many PAH patients is similar to that of
some advanced cancers, and with current treatment options, the five-year
survival rate is 50%(3).
Imatinib mesylate 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(3). In
patients with PAH, PDGFR may cause smooth muscle cells in the pulmonary
arteries to multiply, resulting in the constriction of these arteries(4).
Plans for research to further explore the potential of imatinib
mesylate 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
mesylate 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 mesylate in PAH in a larger randomized clinical trial."
1. It is estimated that approximately 130,000 to 260,000 people worldwide
have PAH(5). 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(4).
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(3).
1. Novartis has also conducted early stage research with imatinib mesylate
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(6). Early clinical trial results in
IPF did not show a significant treatment benefit over placebo, and
clinical trials have therefore been halted.
About Gleevec
Gleevec(R) (imatinib mesylate) tablets are indicated for the treatment
of newly diagnosed adult patients with Philadelphia chromosome-positive
chronic myeloid leukemia (Ph+ CML) in the chronic phase. Follow-up is
limited to 5 years. Gleevec is also indicated for the treatment of patients
with Ph+ CML in blast crisis (BC), accelerated phase (AP), or in chronic
phase (CP) after failure of interferon-alpha (IFN-alpha) therapy; adult
patients with relapsed or refractory Ph+ acute lymphoblastic leukemia (Ph+
ALL); adult patients with myelodysplastic/myeloproliferative diseases
(MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor)
gene rearrangements; adult patients with aggressive systemic mastocytosis
(ASM) without the D816V c-KIT mutation or with c-KIT mutational status
unknown; adult patients with hypereosinophilic syndrome (HES) and/or
chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFR???± fusion
kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion)
and for patients with HES and/or CEL who are FIP1L1-PDGFR???± fusion
kinase-negative or unknown; adult patients with unresectable, recurrent,
and/or metastatic dermatofibrosarcoma protuberans (DFSP); patients with KIT
(CD117)-positive unresectable and/or metastatic malignant gastrointestinal
stromal tumors (GIST); pediatric patients with PH+ CML in the chronic phase
who are newly diagnosed or whose disease has recurred after stem cell
transplant or who are resistant to interferon-therapy. There are no
controlled trials in pediatric patients demonstrating a clinical benefit,
such as improvement in disease-related symptoms or increased survival.
Important safety information(7)
Fetal harm can occur when Gleevec is administered to a pregnant woman;
therefore, women of childbearing potential should be advised to not become
pregnant while taking Gleevec tablets and to avoid breast-feeding while
taking Gleevec tablets because of the potential for serious adverse
reactions in nursing infants. Sexually active female patients taking
Gleevec should use adequate contraception. If the patient does become
pregnant while taking Gleevec, the patient should be advised of the
potential hazard to the fetus.
In adult Ph+ CML patients, severe (NCI Grades 3/4) lab
abnormalities–including neutropenia (3.6%-48%), anemia (1%-42%),
thrombocytopenia (generic cialis online buy | Generic acomplia pills no prescription | Buy ultram pills