Drug based on MGH discovery may significantly improve treatment of dangerous blood disorder

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Novel agent increases platelet production in clinical trials

Two clinical trials of the novel drug romiplostim (Nplate) show that it significantly improved platelet levels in patients with chronic immune thrombocytopenic purpura (ITP), a hematologic disorder that can cause uncontrolled bleeding.  An international research team reports Phase 3 trial results for the drug, which duplicates the action of a natural hormone discovered by a Massachusetts General Hospital (MGH) investigator, in the February 2 issue of The Lancet.

“Many ITP patients have had to choose between no therapy or a treatment with limited efficacy and potentially serious side effects,” says David Kuter, director of Clinical Hematology at MGH and lead author of the Lancet study.  “The low toxicity and high response to this drug may convert a potentially life-threatening condition to one that can be easily managed with a weekly injection.” 

ITP is a chronic disorder in which the immune system destroys platelets, blood cells that help prevent bleeding.  While some ITP patients experience only increased bruising, others may have serious bleeding and occasionally dangerous hemorrhage.  Recent investigations suggest that, in addition to the destruction of existing platelets, ITP also may be due to reduced platelet production.  Currently available treatments for ITP – including steroid drugs, which have significant side effects, and removal of the spleen (splenectomy) – are designed to reduce platelet destruction and may be ineffective in many patients. 

Thrombopoietin is the natural regulator of platelet production.  Kuter was one of the original discoverers of the hormone in 1994 and has been active in developing thrombopoietic drugs ever since.  Romiplostim is a unique ‘peptibody’ – a peptide antibody – that stimulates platelet production by mimicking the action of thrombopoietin.  Earlier Phase 1 and 2 trials have shown that romiplostim increases platelet production in healthy volunteers and in short-term treatment of ITP patients. 

The double-blinded Phase 3 trials were conducted at 35 sites in the U.S. and Europe.  One trial enrolled 63 splenectomized patients, the other included 62 patients who retained their spleens. Both groups were randomly assigned to receive either romiplostim or a placebo in weekly injections during the 24-week study period. Participants’ platelet levels were monitored during the trial, and dosage was adjusted to achieve a target platelet count of 50,000/ml.

Among the 42 splenectomized patients who received romiplostim, nearly 80 percent reached the target platelet count during at least four weeks of the study, and 38 percent achieved a durable response, maintaining a target platelet count during at least six of the last eight weeks of the study.  In the non-splenectomized patients, 88 percent had at least four target platelet count measurements, with 61 percent achieving a durable response. 

More than half the patients receiving romiplostim were able to discontinue all other ITP medications they were taking, and 35 percent reduced other therapies.  While over half the participants in the placebo groups of both studies needed rescue medications to treat or prevent bleeding episodes, significantly fewer of those receiving the active medication needed such treatment.

“We’re seeing dramatic results for this totally new approach to treating people with ITP,” Kuter says.  “I’ve been working on the development of thrombopoietin since 1983, and it’s very gratifying to participate in its discovery, purification, drug development and now the studies showing its clinical effectiveness.”   He adds that his MGH team and other researchers are conducting other romiplostim trials and will continue to investigate the drug’s usefulness for treating ITP and other conditions of reduced platelet production, such as those caused by cancer or cancer treatment. 

Kuter is also director of Hematology for the MGH Cancer Center and an associated professor of Medicine at Harvard Medical School. The Lancet study was designed and supported by Amgen Inc., which developed romiplostim, has applied for FDA approval and plans to market the drug under the brand name Nplate.  Kuter had full access to the study data and overall responsibility for submitting the report for publication.