Researchers evaluated new approaches to managing major bleeding and clotting diseases.
Amgen Inc. scientists reported data from a randomized, pivotal Phase III study showing that their novel 'peptibody' AMG 531 (romiplostim) boosts and sustains platelet counts in splenectomized adult patients with chronic immune thrombocytopenic purpura (ITP)-an autoimmune disorder characterized by low blood platelet numbers, bruising, and bleeding. It affects about 200,000 Americans and a similar number of Europeans.
Also found was that some patients receiving romiplostim together with standard treatments (e.g., corticosteroids) could stop taking the latter.
"Patients with chronic ITP produce antiplatelet autoantibodies that destroy their blood platelets and, at times, also damage their megakaryocytes (cells that produce platelets in the bone marrow)," she explained. "Splenectomy, high-dose steroids, androgens, and newer immunosuppressive drugs treat refractory ITP – but not always successfully. Some experts say splenectomy succeeds in 60% of cases; others say, much less often....
"Romiplostin is an investigational therapy that stimulates platelet production at the thrombopoietin receptor," continued Gernsheimer. "Thrombopoietin is a hormone that encourages the bone marrow to produce platelets."
Amgen recently filed for regulatory approval of romiplostin to treat adult thrombocytopenia in the United States, European Union (EU), Australia, Canada, and Japan. The drug has orphan designation in all those areas, Gernsheimer pointed out.
In her team's pivotal 63-patient Phase III study reported in a plenary session at ASH, either romiplostin or placebo was injected weekly for 24 weeks at a starting dose of 1mcg/kg, and adjusted to maintain a target platelet count based on weekly response.
Some 78% of patients receiving the study drug responded to it versus none in the placebo group. Additionally, patients treated with romiplostin needed less frequent use of rescue medications than those on placebo, and reduced their use of concurrent ITP therapies as well.
Gernsheimer emphasized: "[Before treatment with romiplostim] these patients continued to suffer low platelet counts after a median of 7.75 years of having chronic ITP and more than five major treatments including splenectomy....."
Although romiplostin was well tolerated, one patient experienced thrombosis and one developed increased reticulin in the bone marrow-both briefly, she noted. The most common minor side effects were headache, dizziness, and myalgia.
In a related report, GlaxoSmithKline announced findings on the long-term safety and efficacy of its investigational agent Promacta (eltrombopag), an oral platelet growth factor to treat ITP. The results showed that:
The study is designed to assess the potential of eltrombopag as an oral treatment for improving platelet numbers in patients with chronic ITP.
"The findings are hopeful," said principal investigator James B. Bussell, M.D., director, Platelet Disorders Center, Weill/Cornell/Presbyterian Hospital, New York. "They suggest that Promacta, once approved, may provide physicians with a different treatment option to raise and maintain patients' platelet levels and alleviate their ITP symptoms."
As yet, however, the drug has received no regulatory approval in any market.
Eltrombopag was fairly well-tolerated in this study, Bussell added. Of the 94 patients who received at least one dose, 83% reported at least one adverse event (AE)-"but most AEs were mild, with the most common being headache (20%)," he said.
THE AUTHOR is a writer based in New York.