GSK Initiates REPEAT Dosing Study Of Its Novel Oral Platelet Growth Factor, PROMACTA(R), In ITP

GlaxoSmithKline plc today
announced the initiation of a global, open-label, single group trial that
will assess the efficacy, safety and tolerability of PROMACTA(R)
(eltrombopag olamine) in patients previously treated for chronic idiopathic
thrombocytopenic purpura (ITP). The trial, called REPEAT (Repeat ExPosure
to Eltrombopag in Adults with Idiopathic Thrombocytopenic Purpura), will
evaluate a repeated dosing schedule of three six week cycles of PROMACTA
treatment in 50 patients with chronic ITP who will be enrolled at multiple
centers.


"The current treatment approaches to acutely increase the platelet
count typically include treatment with steroids or IV gammaglobulin, both
of which may have issues with tolerability or safety," says James B.
Bussel, MD, Director of the Platelet Disorders Center, Children's Blood
Foundation Division at the New York-Presbyterian Hospital/Weill Cornell
Medical Center and investigator for this trial. "Due to patients' varying
clinical circumstances, it is important to validate the safety and
effectiveness of repeated short-term treatment with eltrombopag in patients
with chronic ITP."



ITP is estimated to affect 50 to 100 new persons per million per year
in the United States and Europe.(1) People with ITP often bleed from small
blood vessels underneath the skin causing bruises, nosebleeds, bleeding
from the gums during dental work, or other bleeding that is difficult to
stop. Bleeding in the brain or gastrointestinal (GI) tract is rare but can
be life threatening if it occurs.(2) Although this condition can be managed
chronically, it is associated with significant mortality and morbidity --
5% of patients will die within ten years of diagnosis, primarily from
intracranial hemorrhage.(3)



Initiation of the REPEAT trial follows completion of a Phase II study
that evaluated 117 patients with chronic ITP and low platelet levels
(50mg over six weeks.(3) In Phase II,
PROMACTA was not associated with an increased incidence of adverse events
(AEs) compared to placebo across the 30mg, 50mg and 75mg eltrombopag
treatment arms. Bleeding adverse events included the following:
hemorrhoids, hemorrhagic diarrhea and conjunctival hemorrhage in 3 patients
receiving placebo; epistaxis, gingival bleeding and contusions in 5
patients receiving 30mg of PROMACTA; menorrhagia in 1 patient receiving
50mg of PROMACTA; and contusion in 1 patient receiving 75mg of PROMACTA.
All 7 patients who received PROMACTA and bled were non-responders. The most
common AE observed in this study was mild to moderate headache, reported in
21% of subjects on placebo, and 13%, 10% and 21% of subjects in the 30mg,
50mg and 75mg PROMACTA arms, respectively.(3)
















"We are extremely encouraged by the continued progress in our PROMACTA
clinical development program", said Paolo Paoletti, MD, Senior Vice
President, Oncology Medicine Development Center, GSK. "We continue to be
very optimistic about PROMACTA and we expect results from this trial will
represent another step towards providing patients with a safer, more
effective ITP treatment."



In December 2006, GlaxoSmithKline announced the initiation of a Phase
III trial assessing the safety, efficacy and tolerability of PROMACTA in a
long- term setting (up to six months) in previously treated patients with
chronic ITP. Long-term ITP treatment may be necessary in patients with
consistently low platelet levels and current treatment options such as
steroids have draw- backs if used on a long-term basis. Therefore, it is
important to evaluate PROMACTA in this setting.(4)



Results from other studies involving PROMACTA will be presented at
international medical congresses in the near future and additional studies
are ongoing and planned in ITP and other conditions where thrombocytopenia
is an issue. PROMACTA is an investigational agent that is not approved for
use in any market for any indication at this time.



Study Design



The REPEAT trial will assess the efficacy, safety, and tolerability of
three repeated dosing cycles of PROMACTA in patients previously treated for
chronic ITP, examples of which include splenectomy, corticosteroids,
immunoglobulins, cyclophosphamide or rituximab. The primary objective is to
evaluate the effect of PROMACTA on platelet counts during three consecutive
treatment cycles. Secondary objectives include evaluating incidence and
severity of bleeding, as well as the frequency of adverse events.



About PROMACTA



PROMACTA is a non-peptide thrombopoietin receptor agonist that has been
shown in pre-clinical research and clinical trials to stimulate the
proliferation and differentiation of megakaryocytes, the bone marrow cells
that give rise to blood platelets, and thus maybe considered a platelet
growth factor. PROMACTA is administered orally as a once a day tablet. The
safety profile will be further examined in the ongoing clinical trials.
PROMACTA was discovered as a result of a research collaboration between
GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by
GlaxoSmithKline. PROMACTA is an investigational compound that has not
received regulatory approval in any market for any indication at this time.



About Idiopathic Thrombocytopenia Purpura (ITP)



ITP is characterized by increased autoimmune platelet destruction
and/or inadequate platelet production. Its cause is currently unknown. Some
patients with ITP are asymptomatic or have mild bruising while others
develop mucosal bleeding that can become severe.(5) A normal blood platelet
count is greater than or equal to 150,000/microliter and less than or equal
to 400,000/microliter.(6) A reduction in platelet count (to a level
Buy Nimotop Without Prescription