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Dosing convenience mandates
the pipeline of glucagon-like peptide-1 (GLP-1) analogs for type 2 diabetes
Twice-daily injection is the
benchmark set by exenatide, the first GLP-1 analog launched in the US by Lilly
in June 2005 and half-year sales of US$ 74.6 mln, which now faces competition by
GLP-1 analog treatment modalities with less frequent dosing.
Barcelona, Spain, Feb 6, 2006: The Business Intelligence firm La
Merie S.L. reported today that twice-daily injection is the benchmark set by
exenatide, the first GLP-1 analog launched in the US by Lilly in June 2005 and
half-year sales of US$ 74.6 mln, which now faces competition by GLP-1 analog
treatment modalities with less frequent dosing. More convenience is brought to
patients with once-daily dosing from the closest competitor (Novo Nordisk) which
Lilly counters with a once-a-week injectable drug delivery. Other competitors
follow with sustained release formulations of GLP-1 analogs or develop a nasal
spray GLP-1 analog as a non-invasive alternative to injections. Another, yet IND
or preclinical stage approach is the development of fusion proteins of GLP-1
with large carrier proteins such as albumin or transferrin leading to even
longer half-lives, thus potentially allowing dosing every 2 or 3 weeks. These
results were found in a search conducted by La Merie Business Intelligence
published in the February 6 issue of R&D Pipeline News, edited by La Merie, and
can be acquired as a Project Pipeline List at www.pipelinereview.com.
Both enzymatic cleavage and renal clearance contribute to a very short
circulating half-life of several minutes for native GLP-1 which is a 30-amino
acid gut peptide produced in enteroendocrine cells located in the distal ileum
and colon. Thus, GLP-1 analogs have been constructed with resistance to
enzymatic cleavage. These GLP-1 mimetics bind to GLP-1 receptors with similar
affinity and produce biological actions identical to those of native GLP-1 which
controls blood glucose via multiple actions including stimulation of insulin
secretion and inhibition of both glucagon secretion and gastric emptying.
Preclinical data suggest that GLP-1 analogs engage signaling pathways in the
islet beta-cell that lead to stimulation of beta-cell replication and inhibition
of beta-cell apoptosis. However, it remains to be proven clinically whether GLP1
analogs may reverse the decline in beta-cell mass of the pancreas that is
characteristic of the natural history of type 2 diabetes.
Exenatide from Lilly is approved for use in patients with type 2 diabetes who
exhibit unaceptable glycemic control whil using meformin and/or sulfonylurea.
GLP-1 analog therapy clinically has shown the advantage of reducing body weight,
but is associated with nausea and vomiting as the most common adverse effects
which might be reduced with optimized dosing regimens.
Apart from use of GLP-1 analogs in the treatment of diabetes, its usefulness
currently is being investigated in clinical studies of irritable bowel syndrome
and functional dyspepsia. Further studies explore the effects of natural GLP-1
and of AC2592 from Amylin Pharmaceuticals administered by continuous infusion in
patients with congestive heart failure.
About La Merie
La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide
high quality R&D information to the biopharmaceutical industry. La Merie offers
individual consultancy services and publishes reports and periodicals.
They publish two weekly
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R&D Pipeline News is a premier
information source about research and development projects in the pipeline of
the biopharmaceutical industry and is directed to all stakeholders in R&D. The
weekly publication comes in a rapid- and easy-to-screen tabular format and
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