Drug based on MGH discovery may significantly
improve treatment of dangerous blood disorder
Novel agent increases platelet
production, decreases need for other medications
BOSTON - January 31, 2008 - 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, MD, DrPhil, 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 associate 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.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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