Lilly Will Submit Ruboxistaurin Mesylate (Arxxant(TM)) to FDA for Treatment of Diabetic Retinopathy in 2005
August 02 2005 - 10:00AM
PR Newswire (US)
Company Will Not Pursue Submission for Treatment of Symptoms of
Diabetic Peripheral Neuropathy INDIANAPOLIS, Aug. 2
/PRNewswire-FirstCall/ -- Eli Lilly and Company announced today
that it has completed a Phase 3 clinical trial in which its
investigational drug, ruboxistaurin mesylate (proposed brand name
Arxxant(TM), pronounced ark-ZONT) reduced the occurrence of vision
loss in patients with diabetic retinopathy (DR). As a result, Lilly
believes it is appropriate to submit a new drug application (NDA)
to the U.S. Food & Drug Administration (FDA) at the end of 2005
for the treatment of DR, the initial indication for ruboxistaurin.
In addition Lilly is announcing today that two Phase 3 clinical
trials to determine the effect of ruboxistaurin on treatment of
sensory symptoms associated with diabetic peripheral neuropathy
(SDPN) have been completed. In these studies, statistical
comparison of the change in sensory symptom scores between the
placebo and ruboxistaurin-treated groups did not demonstrate
significant differences and did not meet the studies' primary
endpoints -- a regulatory requirement for submission. Consequently,
these results do not support the NDA filing for SDPN. Importantly,
however, no significant safety issues were discovered during these
clinical trials that would preclude continued clinical development.
"While we are disappointed in the outcome of the trials for SDPN,
we are extremely pleased to be one step closer to providing a
possible solution for patients with diabetic retinopathy," said Dr.
Steven Paul, Executive Vice President, Science and Technology, Eli
Lilly and Company. "If ruboxistaurin is approved by the FDA, it
would be the first oral medication for the treatment of this
serious complication of diabetes," he added. Results of these Phase
3 clinical trials will be presented at a future major medical
meeting in late 2005 or early 2006. In addition, it is Lilly's
policy to publish the results of all clinical trials; however,
specific publication plans have not yet been determined. "Since
Lilly has been the industry leader in pioneering diabetes therapies
for more than 80 years, we believe in the value of innovation and
the need for new treatments for this epidemic disease," said Sidney
Taurel, Lilly Chairman, President and Chief Executive Officer. "And
ultimately, the results from these studies serve as a reminder of
the high risks and high rewards associated with pharmaceutical
innovation," he added. About Diabetic Microvascular Complications
Diabetic retinopathy and diabetic peripheral neuropathy (DPN) are
diabetic microvascular complications (DMCs). Nearly 75 percent of
all people with diabetes have at least one DMC. And while tight
blood glucose control (keeping blood sugar at near-normal levels)
lowers the risk of DMCs, there are currently no treatments or
medications approved in the United States to target the underlying
causes of DR and DPN. Eventually, DR can lead to loss of vision or
blindness, and DPN can lead to the amputation of toes, a foot or a
leg. Diabetic retinopathy (DR) is a condition that leads to
progressive damage to the small blood vessels of the eye, and can
lead to vision loss and possible blindness. According to the World
Health Organization and the American Diabetes Association, DR is
the leading cause of vision loss in adults of working age (20 to 65
years) in industrialized countries. Ruboxistaurin was studied in a
Phase 3 clinical trial of 685 patients with moderately severe to
severe, non-proliferative DR. The primary objective of this trial
was to test the hypothesis that once-daily oral administration of
ruboxistaurin over three years would reduce the occurrence of
sustained moderate visual loss (equivalent to doubling of the
visual angle, such as a reduction in visual acuity from 20/20 to
20/40) in these patients. This trial demonstrated a statistically
significant reduction in this outcome. An ongoing trial to
determine the effect of ruboxistaurin on diabetic macular edema
(DME, a manifestation of DR) progression in patients with less
severe DR is expected to be complete in 2010. Diabetic peripheral
neuropathy (DPN) is a progressive disorder resulting in the
deterioration of nerve function, the clinical manifestations of
which may include subjective sensory symptoms such as numbness,
tingling and pain. Ruboxistaurin was studied in two clinical
trials, involving more than 500 patients combined, for the
treatment of SDPN. These studies had a duration of one year, and
the change in sensory symptom scores was the primary outcome
measure. Statistical comparison of the change in sensory symptom
scores between the placebo- and ruboxistaurin-treated groups did
not demonstrate significant differences. An ongoing, three-year,
placebo-controlled trial evaluating ruboxistaurin for the treatment
of nerve dysfunction of diabetic peripheral neuropathy (DPN),
scheduled to complete in 2007, will continue. In contrast to the
just-completed SDPN trials, change in a composite of objective
nerve function measures is the primary outcome measure of the DPN
trial. About Ruboxistaurin Ruboxistaurin is a specific protein
kinase C beta (PKC beta) inhibitor, the first of a new class of
compounds being investigated for the treatment of diabetic
retinopathy (DR) and diabetic peripheral neuropathy (DPN). In
addition, Lilly has recently presented results of a pilot study of
ruboxistaurin in patients with diabetic nephropathy (kidney disease
or DN) at a major medical meeting. These are the three major
diabetic microvascular complications (DMCs) associated with type 1
and type 2 diabetes. Metabolic factors associated with diabetes
often lead to damage to the small blood vessels in the eyes, nerves
and kidneys, ultimately leading to DMCs. Pre- clinical data show
that ruboxistaurin is a specific inhibitor of PKC beta. PKC beta is
an enzyme that has been implicated in the underlying process of
microvascular damage caused by diabetes. Lilly, a leading
innovation-driven corporation, is developing a growing portfolio of
first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories
and from collaborations with eminent scientific organizations.
Headquartered in Indianapolis, Ind., Lilly provides answers --
through medicines and information -- for some of the world's most
urgent medical needs. Additional information about Lilly is
available at http://www.lilly.com/. This press release contains
forward-looking statements about the potential of the
investigational compound ruboxistaurin for the treatment of
diabetic microvascular complications and reflects Lilly's current
beliefs. However, as with any pharmaceutical product under
development, there are substantial risks and uncertainties in the
process of development and regulatory review. There is no guarantee
that the product will receive regulatory approvals, or that the
regulatory approval will be for the indication(s) anticipated by
the company. There is also no guarantee that the product will prove
to be commercially successful. For further discussion of these and
other risks and uncertainties, see Lilly's filings with the United
States Securities and Exchange Commission. Lilly undertakes no duty
to update forward-looking statements. P-LLY F-LLY (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Marni Lemons of Eli Lilly and
Company, +1-317-433-8990 (office), +1-877-970-7380 (pager)
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