ASH: Oral Drug Boosts Platelet Counts for ITP

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ASH: Oral Drug Boosts Platelet Counts for ITP

By Neil Osterweil, Senior Associate Editor, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine. December 12, 2006

ORLANDO, Dec. 12 -- An investigational oral platelet growth factor increased platelet counts in patients with chronic idiopathic thrombocytopenic purpura (ITP) reported investigators here.In multinational randomized controlled trials, Promacta (eltrombopag) increased counts by about a factor of 10 when delivered at the highest dose to patients with ITP, said B. Bussel, M.D., director of the Platelet Disorders Center at the Weill Cornell Medical Center in New York.

"We believe that this will be a major new advance in the management of ITP," Dr. Bussel said at the American Society of Hematology meeting here.

"It confirms a previous study that you can treat ITP by stimulating the platelet count," he added. "Previous studies had all basically focused on slowing down the rate of platelet destruction, and the advantage of this particular agent is that it can be given orally once a day."

Promacta is a thrombopoeitin receptor agonist that has been shown in both preclinical studies and clinical trials to stimulate proliferation and differentiation of megakaryocytes. Because it is a relatively small molecule therapeutic, it has less potential than large peptides to evoke an immune reaction, according to investigators.

The Phase II trial was an international randomized, double-blind, placebo-controlled study in 117 adult patients with chronic ITP (more than six months), with baseline platelet counts of less than 30,000/μL.

The patients were randomly assigned to Promacta orally once daily in doses of 30, 50 or 75 mg, or to placebo, for six weeks. The investigators assessed bleeding events weekly during treatment and biweekly after treatment using adverse event reporting and the WHO bleeding scale, which measures bleeding severity from Grade 0 (no bleeding) through to Grade 4 (debilitating blood loss).

The study was planned to have an enrollment of 270 patients, but was stopped at the first interim analysis for efficacy, of both the 50- and 75-mg doses (P<0.001), Dr. Bussel said.

More than 70% of patients at the 50-mg dose and more than 80% of patients at the 75-mg dose met the primary response criteria of the study, which was a platelet count of more than 50,000 after six weeks of therapy.

"Approximately 40% of the patients at these two doses had to stop dosing during the study, because their platelet counts went over 200,000, and therefore they were taken off treatment, though they were monitored for the rest of the study," Dr. Bussel said.

The occurrence of on-treatment bleeding events was 16% in patients on the 30-mg Promacta arm, 3% in the 50-mg arm, 4% in the 75-mg arm, and 10% in the placebo arm.

The median platelet count on day 43 of treatment was 26,000/μL for 30 mg Promacta, 128,000/μL for 50 mg, 183,000/μL for 75 mg of Promacta, compared with 16,000/μL for placebo.

Bleeding adverse events included hemorrhoids, hemorrhagic diarrhea, and conjunctival hemorrhage in three patients on placebo; epistaxis, gingival bleeding and contusions in five patients receiving 30 mg of Promacta; menorrhagia in one patient receiving 50 mg of Promacta (a non-responder); and contusion in one patient on the 75 mg dose.

The most common adverse event was mild to moderate headache, which occurred in 21% of patients both on placebo and the 75-mg dose of Promacta, in 13% of patients on the 30 mg dose, and in 10% of those on the 50 mg dose.

There was no apparent relationship between the dose and incidence of adverse events in the study.

Clinical trials of Promacta are continuing for ITP and other conditions where thrombocytopenia is of concern, such as chemotherapy and liver disease.

http://www.medpagetoday.com/MeetingCoverage/ASHHematology/dh/4678