Phase 2a Findings Demonstrate that CSL112, A Novel Apolipoprotein A-I Infusion
Therapy, Has a Favorable Safety Profile, is Well Tolerated and Increases
Cholesterol Efflux Capacity in Stable Atherothrombotic Patients
Multiple presentations of study results at the American Heart Association 2013
DALLAS, Nov. 20, 2013
DALLAS, Nov. 20, 2013 /PRNewswire/ --Results of a Phase 2a trial of CSL112,
sponsored by CSL Limited, demonstrated favorable safety and tolerability when
administered to patients with stable atherothrombotic disease. The trial data
for CSL112 also showed a dramatic and rapid increase in key biomarkers of
reverse cholesterol transport, a process by which cholesterol is removed from
arteries and transported to the liver for clearance.
"We are encouraged by the positive safety profile observed in the trial which
supports progression of the CSL112 clinical development program," said
Pierluigi Tricoci, MD, PhD, MHS, Duke Clinical Research Institute, and lead
study author. "We know there is a need for novel approaches to reduce the high
risk of early recurrent ischemic events after acute coronary syndrome. CSL112
is a promising treatment targeting coronary atherosclerotic plaques causing
these events and deserves further investigation."
Three separate analyses of data from the CSL112 Phase 2a study were presented
at the American Heart Association 2013 Scientific Sessions. The presentations
examined the safety and tolerability, pharmacokinetics and lipid biomarker
profile, and potential antiplatelet effects of CSL112 on top of dual
Study Design and Key Findings
The CSL112 Phase 2a study was a randomized, multicenter, double-blind,
placebo-controlled trial (n=44) that evaluated the safety and
pharmacokinetics/pharmacodynamics (PK/PD) of a single-dose administration of
CSL112 in patients with stable atherothrombotic disease. Patients were
randomized to a single infusion of either CSL112 at 1.7, 3.4 or 6.8g doses or
masked placebo. PK and PD were assessed up to 7 days after the infusion during
the active treatment period. Safety was assessed for up to 90 days after the
No treatment-emergent serious adverse events (AE) were reported during the
active treatment period except for one case of atrial fibrillation which
occurred in the placebo group. Assessments of liver function and other key
biochemical, hematologic and immunogenic measurements over time were similar
across all CSL112 and placebo groups.
PK and PD analyses showed that CSL112 caused immediate and robust increases in
apoA-I, the active component of high density lipoprotein (HDL). Blood levels
of apoA-I rose in a dose-proportional fashion with elevations approaching
three-fold baseline levels at the top dose. The highly anti-atherosclerotic
form of HDL known as PreBeta1 showed an even greater elevation, with increases
up to 17-fold. CSL112 also enhanced key biomarkers of the early steps of
reverse cholesterol transport with strong elevations in cholesterol efflux
capacity observed across all CSL112 regimens. Changes were maintained for up
to 72 hours after infusion of CSL112 at the higher doses.
Potential antiplatelet effects of CSL112 were also evaluated in this
population of patients who were receiving chronic dual antiplatelet therapy.
CSL112 did not significantly influence platelet aggregation in response to AA,
ADP and collagen. Based on these data, it is anticipated that CSL112 will not
affect hemostasis when administered with concomitant antiplatelet therapies.
"Patients who experience an ACS event have a great unmet need to reduce the
risk of suffering another heart attack, stroke or other cardiovascular event,
particularly within the first 30 days," said Chuck Shear, CSL Cardiovascular
Therapeutic Area Head. "The results of this third clinical study of CSL112
support our continued enthusiasm for its development as a novel approach to
address this important therapeutic void."
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I), the active
component of high-density lipoprotein (HDL). It is purified from human plasma
and reconstituted to form HDL particles suitable for intravenous infusion.
Studies have shown the infusion of CSL112 rapidly elevates markers of reverse
cholesterol efflux, a process by which cholesterol is removed from arteries
and transported to the liver for clearance. CSL112 may offer a novel option
for rapidly stabilizing atherosclerotic lesions and is being studied for
reduction in the risk of early atherothrombotic events in acute coronary
syndrome (ACS) patients.
Headquartered in Melbourne, Australia, CSL Limited is a global
biopharmaceutical company that develops, manufactures and markets biotherapies
to prevent and treat rare and serious human diseases. CSL owns major
facilities in Australia, Germany, Switzerland and the United States, and
employs over 11,000 people in more than 25 countries. Visit www.csl.com.au for
Sheila A. Burke
Director, Communications & Public Relations
Worldwide Commercial Operations
MCS Healthcare Public Relations
SOURCE CSL Limited
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