Isis Highlights New Data on Antisense Drugs to Treat Type 2 Diabetes and Obesity From Its Broad Metabolic Disease Franchise at ADA Scientific Sessions
ORLANDO, Fla. and CARLSBAD, Calif., June 29
/PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (NASDAQ:ISIS) announced today that data from
seven programs in Isis' broad metabolic disease franchise were
presented at the American Diabetes Association's (ADA) 70th
Scientific Sessions in Orlando. These presentations included two
oral talks highlighting data from Isis' Phase 2 study of ISIS
113715 in patients with type 2 diabetes and Isis' Phase 1 study of
ISIS-GCGRRx. Isis and collaborators also presented new data from
five other programs demonstrating that antisense drugs can approach
novel targets to treat metabolic diseases and may provide new
therapeutic options for patients.
In the oral presentation titled "ISIS 113715, a Novel PTP-1B
Antisense Inhibitor, Improves Glycemic Control and Dyslipidemia and
Increases Adiponectin Levels in T2DM Subjects Uncontrolled on
Stable Sulfonylurea Therapy," Dr. Sanjay Bhanot presented the
results of a Phase 2 study evaluating ISIS 113715 in patients with
type 2 diabetes whose glucose levels were uncontrolled despite
being treated with maximum doses of sulfonylureas. The study
produced the following results:
-- Statistically significant reductions in multiple short and intermediate measures of glucose control at the 200 mg/week dose -- Statistically significant decrease of approximately 11 mg/dL in LDL Cholesterol -- Reduction in body weight that was preceded by a statistically significant increase in circulating adiponectin, supporting the role of PTP-1B in the regulation of body weight -- No clinically significant adverse events or observations of hypoglycemia. The most common adverse event was mild injection site reactions.
"We have demonstrated that our PTP-1B inhibitor has a very
attractive profile in two Phase 2 studies in patients with type 2
diabetes. A novel insulin sensitizer that reduces high blood
glucose without resulting in hypoglycemia, reduces LDL-cholesterol
and decreases weight would be a significant advance in the
treatment of type 2 diabetes," said Sanjay Bhanot, M.D., Ph.D.,
Vice President of Metabolics and Translational Medicine at Isis.
"In this study, we observed reductions in multiple measures of
glucose control that were consistent with our expectations for a
13-week study. We believe that with longer-term treatment we should
also see reductions in longer-term measures of glucose control. We
are excited to continue to move this program forward and to
evaluate PTP-1B inhibition in longer studies in combination with
other commonly prescribed type 2 diabetes drugs."
In the oral presentation titled "First Proof of Pharmacology of
a Novel Glucagon Receptor Antisense Drug in Humans," Dr. Bhanot
presented the results of a Phase 1 study on ISIS-GCGRRx. The study,
which included a glucagon challenge that doubled both plasma
glucagon and glucose levels, produced the following results:
-- Statistically significant improvement in blood glucose levels and reduced liver glucose production following the glucagon challenge at a dose of 400 mg/week -- No clinically significant adverse events or observations of hypoglycemia. The most common adverse event was mild injection site reactions.
"In our Phase 1 study of ISIS-GCGRRx we achieved reductions in
blood glucose following a glucagon challenge. This result supports
the therapeutic potential of inhibiting the glucagon receptor.
Glucagon is thought to play a greater role in increasing blood
glucose in patients with advanced diabetes, so a glucagon receptor
inhibitor should work very well in these patients. Based on the
positive data from this Phase 1 study and the therapeutic potential
of a GCGR inhibitor, we are moving the program forward with a more
potent GCGR antisense inhibitor," continued Dr. Bhanot.
"Both ISIS 113715 and ISIS-GCGRRx highlight the multifaceted
approach Isis employs to develop novel new drugs to treat type 2
diabetes. We now have four drugs in our metabolic pipeline, each
with a unique approach to the treatment of type 2 diabetes," added
Isis scientists presented new data from the Company's obesity
drug discovery program, a part of Isis' metabolic disease
franchise. Isis previously reported that antisense reduction of
fibroblast growth factor receptor 4 (FGFR4) lowered body weight and
improved insulin sensitivity in mice, indicating that FGFR4 plays a
role in the regulation of energy expenditure and body weight. In
this study, an antisense inhibitor to FGFR4 and rimonabant, an
appetite-suppressing drug, were administered separately and in
combination in animal models of obesity. The study showed that
antisense inhibition of FGFR4 was complementary to the CNS-based
treatment, rimonabant, suggesting that the peripheral inhibition of
FGFR4 in combination with other types of anti-obesity drugs could
be a unique therapeutic approach for the treatment of obesity and
related metabolic disorders.
"We have made substantial progress in our anti-obesity efforts
over the last couple of years and are moving promising compounds
closer to development. We have adopted a unique approach in this
program. We believe that an anti-obesity drug that works in
peripheral tissues, such as fat and liver, and not in the central
nervous system could provide significant therapeutic benefit
without the side effects that are associated with CNS-acting
agents. We look forward to moving a drug into our development
pipeline soon," concluded Dr. Bhanot.
In total Isis' antisense drugs were highlighted in seven
presentations, including three oral and four poster presentations.
In addition to the oral presentations on ISIS 113715 and
ISIS-GCGRRx, Isis and collaborators highlighted data from antisense
inhibitors to a number of metabolic targets in a variety of animal
models showing that antisense inhibition provided therapeutic
benefit including reductions in fat mass and body weight and
improved glucose metabolism. Complete abstracts for the
presentations can be found on the ADA Web site at
ISIS 113715, a Novel PTP-1B Antisense Inhibitor, Improves
Glycemic Control and Dyslipidemia and Increases Adiponectin Levels
in T2DM Subjects Uncontrolled on Stable Sulfonylurea Therapy (Oral
Authors: T. A. Brandt, S. T. Crooke, E. J. Ackermann, S. Xia, E.
S. Morgan, Q. Liu, R. S. Geary, S. Bhanot.
First Proof of Pharmacology of a Novel Glucagon Receptor
Antisense Drug in Humans (Oral Presentation)
Authors: E. S. Morgan, T. A. Brandt, M. G. J. Van Dongen, B. F.
Geerts, J. Burggraaf, J. A. Romjin, A. F. Cohen, T. A. Watanabe, R.
S. Geary, S. Bhanot.
FGFR4 Antisense Oligonucleotide Potentiates the Anti-Obesity
Effect of Rimonabant in Diet-Induced Obese Mice
Authors: X. X. Yu, L. M. Watts, P. Manchem, B. P. Monia, S.
Bhanot, M. L. McCaleb.
Antisense Reduction of DGAT2 Reduces Body Weight and Improves
Dyslipidemia in High-Fat High-Cholesterol Diet Fed LDLr Knockout
Authors: P. Manchem, X. X. Yu, A. Mullick, S. Booten, S. Murray,
L. M. Watts, B. P. Monia, S. Bhanot.
Reduced Adiposity and Improved Metabolic Profile after Antisense
Reduction of GPAT1 Expression in Mouse Models of Obesity
Authors: X. X. Yu, L. M. Watts, P. Manchen, S. Booten, B. P.
Monia, S. Bhanot.
Knockdown of Nicotinamide N-Methyltransferase (NNMT) Reverses
Authors: D. Kraus, Q. Yang, T. C. Pulinilkunnil, J. T. Rodgers,
B. P. Monia, S. Bhanot, T. C. Becker, O. D. Peroni, P. Puigserver,
B. B. Kahn.
Evidence for a Key Role of Hepatic PEPCK-M in Glucose
Homeostasis In Vivo (Oral Presentation)
Authors: R. Stark, C. N. Feriod, X. Zhao, J. Dong, M. Roden, S.
Bhanot, G. I. Shulman, R. G. Kibbey.
ISIS' METABOLIC FRANCHISE
Isis is pursuing the discovery and development of antisense
drugs to treat metabolic diseases, such as diabetes and obesity.
According to the Centers for Disease Control and Prevention,
diabetes affects more than 20 million people in the U.S. Isis has
four drugs in its pipeline to treat type 2 diabetes, each of which
acts upon targets in the liver, fat tissue or the kidney through
distinct mechanisms to improve insulin sensitivity, reduce glucose
production, or affect other metabolic aspects of metabolic disease.
Isis is developing other drugs aimed at other types of metabolic
diseases, including obesity where a peripherally acting
anti-obesity drug could provide a unique therapeutic approach for
the treatment of obesity and related metabolic disorders.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting its expertise in RNA to discover and develop
novel drugs for its product pipeline and for its partners. The
Company has successfully commercialized the world's first antisense
drug and has 22 drugs in development. Isis' drug development
programs are focused on treating cardiovascular, metabolic and
severe neurodegenerative diseases and cancer. Isis' partners are
developing antisense drugs invented by Isis to treat a wide variety
of diseases. Isis and Alnylam Pharmaceuticals are joint owners of
Regulus Therapeutics Inc., a company focused on the discovery,
development and commercialization of microRNA therapeutics. Isis
also has made significant innovations beyond human therapeutics
resulting in products that other companies, including Abbott, are
commercializing. As an innovator in RNA-based drug discovery and
development, Isis is the owner or exclusive licensee of
approximately 1,600 issued patents worldwide. Additional
information about Isis is available at www.isispharm.com.
This press release includes forward-looking statements regarding
Isis' discovery and development of drugs for metabolic diseases,
including the development, activity, therapeutic potential and
safety of ISIS 113715 and ISIS-GCGRRx in the treatment of type 2
diabetes. Any statement describing Isis' goals, expectations,
financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk
statement. Such statements are subject to certain risks and
uncertainties, particularly those inherent in the process of
discovering, developing and commercializing drugs that are safe and
effective for use as human therapeutics, and in the endeavor of
building a business around such products. Isis' forward-looking
statements also involve assumptions that, if they never materialize
or prove correct, could cause its results to differ materially from
those expressed or implied by such forward-looking statements.
Although Isis' forward-looking statements reflect the good faith
judgment of its management, these statements are based only on
facts and factors currently known by Isis. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Isis' programs are described in
additional detail in Isis' annual report on Form 10-K for the year
ended December 31, 2009 and its most recent quarterly report on
Form 10-Q, which are on file with the SEC. Copies of these and
other documents are available from the Company.
In this press release, unless the context requires otherwise,
"Isis," "Company," "we," "our," and "us" refers to Isis
Pharmaceuticals and its subsidiaries, including Regulus
Isis Pharmaceuticals is a registered trademark of Isis
Pharmaceuticals, Inc. Regulus Therapeutics is a trademark of
Regulus Therapeutics Inc.
Source: Isis Pharmaceuticals, Inc.
CONTACT: Kristina Lemonidis, Director, Investor Relations,
+1-760-603-2490, or Amy Blackley, Ph.D., Assistant Director, Corporate
Communications, +1-760-603-2772, both of Isis Pharmaceuticals, Inc.
Posted: June 2010