Pooled Phase 3 Study of Nplate(TM) (Romiplostim) in Adult Patients with Chronic ITP Published in The Lancet
THOUSAND OAKS, Calif., Jan 31, 2008 (BUSINESS WIRE) -- Amgen Inc. (NASDAQ: AMGN) today announced data from two Phase 3
studies which evaluated the administration of Nplate(TM) (romiplostim)
on increasing and sustaining platelet counts in both splenectomized
(spleen removed) and non-splenectomized patients with chronic Immune
Thrombocytopenic Purpura (ITP). The data will be published in the Feb.
2, 2008, issue of The Lancet.
"Adult ITP is a serious chronic autoimmune disorder characterized
by low platelet counts in the blood, a condition known as
thrombocytopenia," said study investigator David J. Kuter, M.D., D.
Phil., Chief of Hematology, Massachusetts General Hospital, Boston.
"These study findings are encouraging and provide hope that Nplate may
provide physicians with a new therapeutic option for adult patients
with chronic ITP."
The 24-week pooled study was comprised of two parallel Phase 3
trials and included 63 splenectomized patients and 62
non-splenectomized patients with ITP and a mean of three platelet
counts of 30,000 per microliter or less. Patients were randomly
assigned 2:1 to subcutaneous injections of Nplate (n=42 in
splenectomized study and n=41 in non-splenectomized study) or placebo
(n=21 in both studies). The primary endpoints assessed the efficacy of
Nplate as measured by a durable platelet response and treatment
safety. Durable response was defined as a platelet count above 50,000
per microliter during six or more of the last eight weeks of treatment
without rescue therapy ever being administered.
-- Durable Platelet Response: The durable response rate was
significantly greater in patients treated with Nplate compared
to those in the placebo group in both studies (difference in
proportion of splenectomized patients responding 38 percent
(95 percent CI (23.4-52.8 percent); p less than 0.0001);
difference in proportion of non-splenectomized patients
responding 56 percent (95 percent CI (38.7-73.7 percent); p
less than 0.0001)). In the placebo groups, no splenectomized
patients and only one non-splenectomized patient achieved a
durable platelet response.
-- Overall Platelet Response: The overall platelet response
(either durable or transient response, with transient defined
as greater than or equal to 4 weekly platelet responses from
week two to 25) was 88 percent (36/41) in non-splenectomized
patients compared to 14 percent (3/21) in the placebo group;
and 79 percent (33/42) in splenectomized patients given Nplate
compared to no splenectomized patients given placebo (p less
-- Platelet Counts: Nplate-treated patients achieved platelet
counts of 50,000 per microliter or more for an average of 13.8
weeks in the splenectomized group and 15.2 weeks in the
non-splenectomized group compared with 0.2 and 1.3 weeks for
patients in the respective placebo groups.
-- Reduction or Discontinuation of Concurrent Therapies: In both
studies, 23 (12 splenectomized and 11 non-splenectomized)
patients with Nplate and 16 (six splenectomized and 10
non-splenectomized) patients in the placebo group received
concurrent ITP therapy with corticosteroids, azathioprine,
and/or danazol. During the first 12 weeks of the study, 52
percent of the Nplate patients and 19 percent of the placebo
patients discontinued all of their concurrent ITP treatments.
An additional 35 percent of the Nplate patients and 19 percent
of the placebo patients reduced at least one of their
concurrent ITP medicines by more than 25 percent.
-- Rescue Medications: Significantly more patients in the placebo
group received rescue treatment to increase platelet counts to
prevent or treat bleeding compared to the Nplate-treated
patients (57 percent placebo vs. 26 percent Nplate-treated
splenectomized group; 62 percent placebo vs. 17 percent
Nplate-treated non-splenectomized group) (p less than 0.0001).
Rescue medication was defined as an increased dose of
concurrent ITP drug, or the use of any new drug to increase
Adverse event rates were similar between the Nplate and placebo
groups. According to the study authors, a study analysis indicated no
difference in the safety profile between splenectomized and
non-splenectomized ITP patients treated with Nplate, and therefore the
authors pooled safety data for all patients in the Nplate and placebo
In one splenectomized Nplate-treated patient, an increase in bone
marrow reticulin that returned to baseline three months after
withdrawal of Nplate was reported as a treatment-related serious
adverse event. The other treatment-related serious adverse event
reported was a peripheral thrombosis that was successfully treated,
allowing study continuation. Deaths on-study included two patients in
the placebo group and one in the Nplate group.
Significant bleeding events (rated as severe, life-threatening or
fatal) were reported in 12 percent of patients in the placebo group
compared to seven percent of Nplate patients. No patient tested
positive for neutralizing antibodies against thrombopoietin.
The most common adverse events reported in patients treated with
Nplate were headache, fatigue, epistaxis, arthralgia, and contusion.
Amgen filed for regulatory approval of Nplate for use in the
treatment of thrombocytopenia in adults with chronic ITP in the United
States (U.S.) and has received priority review from the U.S. Food and
Drug Administration (FDA). Additionally, Amgen has submitted
regulatory filings for the same indication in the European Union,
Canada and Australia.
Romiplostim is an investigational thrombopoiesis-stimulating
protein Fc-peptide fusion protein ("peptibody") that contains two
component regions. Peptibodies are engineered therapeutic molecules
that can bind to human drug targets and contain peptides linked to the
constant domains of antibodies. Nplate works similarly to
thrombopoietin (TPO), a natural protein in the body. Nplate binds to
the TPO receptor, which activates the pathway necessary for growth and
maturation of bone marrow megakaryocyte cells, resulting in increased
platelet production. In 2004, the FDA granted fast track designation
for Nplate. Orphan designation for ITP was granted in 2003 by the FDA
and in 2005 by the European Agency for the Evaluation of Medicinal
Products (EMEA). Nplate also has received orphan designation for this
proposed indication in Switzerland (2005) and Japan (2006).
About Adult ITP
Adult Immune (Idiopathic) Thrombocytopenic Purpura (ITP) is a
chronic and potentially serious autoimmune disorder characterized by
low platelet counts in the blood, a condition known as
thrombocytopenia. A normal platelet range for a person without ITP is
150,000 - 400,000 platelets per microliter of blood. The risk of a
bleeding event increases when platelet counts drop to less than 30,000
platelets per microliter.
With ITP, platelets are destroyed by the patient's own immune
system. ITP has historically been considered a disease of platelet
destruction; however, recent data also suggest that the body's natural
platelet production processes are unable to compensate for low levels
of platelets in the blood. Increasing the rate of platelet production
may address low platelet levels associated with ITP.
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