T3Therapeutics, LLC
and Archimedes Pharma Ltd Announce Positive Clinical Results
for Novel Oral Modified Release Liothyronine
Results Show
Proof of Concept for Treatment of Congestive Heart Failure
and Hypothyroidism
MANHASSET,
NY and READING, 6th June 2008 – T3Therapeutics,
LLC and Archimedes Development Ltd, a subsidiary of Archimedes
Pharma Ltd the UK-based pan-European specialty pharmaceutical
company, today announced positive clinical data from their
Phase I study evaluating the relative bioavailability of
oral modified release formulations of liothyronine sodium
(T3) compared with oral immediate release T3 tablets in healthy
volunteers. T3 is a hormone produced by the thyroid gland
that is deficient in patients with congestive heart failure
and with hypothyroidism where its deficiency can be associated
with cardiovascular disease.
The results showed the modified
release formulations of T3 produced by Archimedes exhibited
pharmacokinetic profiles with lowered Cmax and prolonged
Tmax compared to oral immediate release formulations while
also maintaining bioavailability. These characteristics have
the potential to greatly improve the clinical effectiveness
of T3 in the treatment of hypothyroidism and expand its use
to congestive heart failure.
A major limitation of current
oral T3 therapy is the reliance on
an immediate release tablet. The combined effects
of rapid absorption and rapid elimination produces wide fluctuations
in T3 levels over a 24-hour dosing
period. Non-physiologic peaks in serum T3 levels
are frequently associated with headache, nervousness, irritability,
and sweating, as well as cardiac arrhythmias including tachycardia. For
the successful treatment of congestive heart failure, circulating
concentration of T3 must be kept
within a narrow and specified therapeutic range.
Dr. Irwin Klein, president of T3Therapeutics
said: “The
results we are announcing today clearly show that a modified
release oral formulation of T3 has the potential to overcome
the side effect profile that limits its current use in hypothyroidism,
where only a small percentage of over 30 million patients
are treated with T3, and also to expand its use as a novel
treatment for congestive heart failure, a condition that
affects more than 5 million patients in the US and UK.”
Alan Smith, Vice President of Research & Development
at Archimedes said: “We are extremely satisfied with
this set of results. It highlights the ability of the Archimedes
team to transform the commercial prospects of molecules which
have yet to achieve their market potential due to their current
mode of delivery. We apply the same philosophy and
proven skills in the development of our own pipeline products,
for example, NasalFent® our
innovative fentanyl citrate nasal spray for the treatment
of breakthrough cancer pain, and also when working with partners
using our core proprietary nasal delivery technologies PecSys™ and
ChiSys®.”
T3Therapeutics
and Archimedes have a worldwide licensing agreement for the
development and commercialisation of a novel oral modified
release formulation of T3 for use in the treatment of congestive
heart failure and hypothyroidism. T3Therapeutics is now seeking
licensees for the further development of the modified release
formulation in North America and Japan.
Study design and results
Archimedes has developed modified release bead formulations
of T3 (MR1 and MR2) utilising extrusion-spheronisation
technology both for use in conventional thyroid therapy
for hypothyroidism and for potential use in the treatment
of congestive heart failure.
This open-label,
single-dose, randomised, crossover, pharmacokinetic proof-of-concept
study was designed to evaluate the relative bioavailability
of oral modified release vs. immediate release T3 in
healthy volunteers. The trial involved 12 subjects, randomly
assigned to a treatment sequence, who each received two
modified release formulations and a marketed immediate
release tablet formulation (Tertroxin®,
Goldshield Pharmaceuticals, UK) at the same 40 mcg dose.
The study was designed to assess pharmacokinetics.
The modified release of T3 was
achieved with a significant reduction in Cmax of
27% (MR1) and 46% (MR2) for the two test formulations relative
to the reference formulation. Both
modified release formulations reached Tmax later
(3.5 hours and 4.4 hours respectively) than the immediate
release formulation (2.4 hours).
The bioavailability of formulation MR1
as measured by the AUC0-t or AUC0-∞ was 86.8% and 91.3%
of the reference formulation and the 90% confidence intervals
fell within the FDA requirements for bioequivalence for
thyroid hormone products.
This news release contains forward-looking statements.
These statements are based upon our current expectations
and speak only as of the date hereof. Our actual results
may differ materially and adversely from those expressed
in any forward-looking statements as a result of various
factors and uncertainties, including the future success
of our clinical studies, our ability to successfully develop
and manufacture products, rapid technological change in
our industry, changes in demand for our future products,
legislative, regulatory and competitive developments and
general economic conditions.
Enquiries
Archimedes: Michael
Clark, +44 (0)118 931 5050
T3Therapeutics: Irwin Klein, President, + (516) 562 4368 (iklein@NSHS.edu)
Citigate Dewe Rogerson: Chris
Gardner/Heather Keohane, +44 (0)207 638 9571
For more information on
Archimedes, visit: www.archimedespharma.com |
