GlaxoSmithKline plc (GSK) today announced that topline results have been
received from seven of the eight ‘Harmony’ Phase III studies investigating the
use of albiglutide in type 2 diabetes.
Albiglutide is an investigational
once weekly glucagon-like peptide-1 (GLP-1) agonist. In Harmony 6, the second of the phase III ‘Harmony’ studies to complete,
albiglutide was compared to preprandial insulin, each administered on top of
long-acting insulin glargine. In this study, the first of its kind for
the class, albiglutide produced clinically significant reductions in HbA1c from
baseline and non-inferiority versus preprandial lispro insulin after 26 weeks
of treatment, achieving the primary endpoint.
Results showed a reduction in HbA1c from baseline of 0.82% for patients
receiving albiglutide compared to a reduction of 0.66% for preprandial lispro
insulin (p<0.0001 for non-inferiority). Weight change from baseline
was -0.73kg in the albiglutide arm and +0.81kg in the preprandial lispro
insulin arm (p<0.0001 for treatment difference). The most common
adverse events observed more frequently in the albiglutide arm than the
comparator arm, in this 52 week study, were gastrointestinal in nature; nausea
(13% for albiglutide versus 2.1% for preprandial lispro insulin) and vomiting
(7% for albiglutide versus 1.4% for preprandial lispro insulin). Initial data from the first study to complete, Harmony 7, a head-to-head
study comparing albiglutide to once-a-day liraglutide, were announced in
November 2011.
Today, GSK also announced that 2 year data read-outs from five ongoing
phase III studies (Harmony 1 through Harmony 5) have been received.
These read-outs present the final results for primary endpoint data up to two
years. As the five ongoing studies have not completed, these data have to
remain confidential to protect the integrity of the ongoing blinded studies and
in line with our agreements with regulators. Nevertheless, the individual
study data provide an early indication of the profile of the investigational
product, broadly aligned with the results of the two completed studies. These
two year data support progression and will be used for regulatory filings.
Harmony 8 will complete in mid 2012 and the five ongoing studies will
complete in early 2013. The Harmony programme was designed to permit assessment
of safety and durability of glycemic control after long-term use. The
studies will provide data on the effect of albiglutide over three years, the
first GLP-1 agonist to do so.
GSK has now reviewed primary endpoint data (6 months to 2 years) on the
efficacy and safety of albiglutide, verses placebo and active controls, across
seven Phase III studies. Based on these data, a better understanding of
the profile of albiglutide in type 2 diabetes is emerging. The data
reviewed to date support progression to regulatory submissions, as a possible
once-weekly treatment for type 2 diabetes. As well as the full data set
from Harmony 6, 7 and 8 and the 2 year data currently in-house from the five
ongoing studies, a meta-analysis of cardiovascular safety data will be required
to complete the registration package, consistent with FDA
guidelines.
GSK anticipates data from both Harmony 6 and Harmony 7 will be presented at
a scientific meeting in 2012. Results from the other six studies will be
submitted for presentation and publication, once the studies complete.
About the Harmony Phase III programme
The Phase III clinical development programme for albiglutide, comprises
eight individual studies, known as Harmony 1 to Harmony 8. The programme is investigating the efficacy, tolerability and safety,
including cardiovascular safety, of albiglutide as mono- and add-on therapy, in
patients with type 2 diabetes. The primary efficacy endpoint for all
studies is the change from baseline in HbA1c compared to placebo and/or active
comparators. A majority of the studies will include active comparators,
including sulphonylurea, thiazolidinedione (TZD), insulin and a dipeptidyl
peptidase four inhibitor (DPP IV).
The individual phase III studies are due to complete from late 2011 through
early 2013. Harmony 6 and Harmony 7 have completed. One study (Harmony 8)
will complete in 2012. The remaining five studies are expected to
complete by early 2013; these ongoing studies have a primary efficacy endpoint
set at between one and two years, and this timepoint has now been reached for
each of these studies. As per the study protocols, these studies will
remain blinded past the primary efficacy endpoint until completion, which for
most studies is three years.
About albiglutide
Albiglutide is an investigational biological, injectable form of human
GLP-1 and is not currently approved anywhere in the world. GLP-1 is a peptide
that acts throughout the body to help maintain normal blood-sugar levels and to
control appetite. Normally, GLP-1 levels rise during a meal to help the
body utilise and control the elevation in blood sugar levels. However,
GLP-1 is rapidly degraded, resulting in its short duration of action. In people
with type 2 diabetes, GLP-1 secretion in response to a meal is
reduced. Albiglutide is an investigational medicine which fuses
human GLP-1 to human albumin. It is designed to have the potential to
extended duration of action and allow for weekly or less-frequent injections.
GSK is developing albiglutide as a once-weekly subcutaneous
injection. All of the medication is contained within a proprietary
injector pen for simple reconstitution and subcutaneous administration using a
fine gauge needle by the patient.