Release Details
Isis Initiates Phase 1 Clinical Trial of SGLT2 Antisense Drug
ISIS-SGLT2Rx - Isis' first kidney-targeted antisense drug for type 2 diabetes enters clinical development
CARLSBAD, Calif.,
"In several preclinical models, we have demonstrated greater than 80
percent reduction of SGLT2 levels in the kidney at low-weekly doses, which
resulted in significant increases in urinary glucose excretion. These changes
were accompanied by robust and sustained decreases in blood glucose levels in
diabetic animals as well as amelioration of diabetic complications such as
cataract formation. Furthermore, ISIS-SGLT2Rx did not reduce blood sugar
levels below normal," said Sanjay Bhanot, M.D., Ph.D., Vice President of
"ISIS-SGLT2Rx is among the most potent antisense drugs Isis has yet
evaluated in preclinical models. The enhanced potency we have observed
supports the possibility of infrequent injectable dosing or, potentially, a
cost effective oral administration for the treatment of diabetes. In
addition, in a Phase 1 study in healthy volunteers, we will be able to gain
valuable information regarding the drug's activity, which we will use to
design a Phase 2 program," said
About SGLT2 and ISIS-SGLT2Rx
SGLT2 is responsible for glucose re-absorption in the kidney and decreasing SGLT2 function promotes glucose excretion to help reduce blood sugar levels, making it an attractive target for the treatment of diabetes. In preclinical studies up to six months in duration, Isis has demonstrated in several animal species that ISIS-SGLT2Rx and other antisense inhibitors of SGLT2 effectively reduce target mRNA levels, increase urinary glucose excretion and consequently lower blood glucose levels and HbA1c without causing any changes in renal or hepatic function or dangerously low levels of blood sugar known as hypoglycemia. Observations in preclinical studies are consistent with expectations based on human subjects who have mutations in the SGLT2 gene and have increased urine glucose levels but are otherwise asymptomatic. ISIS-SGLT2Rx effectively and specifically inhibits the production of SGLT2 in the kidney in animals, and does not have any effect on a related gene product, SGLT1. In addition to being Isis' first second-generation antisense drug for a kidney target, ISIS-SGLT2Rx is also unique due to its 12 nucleotide length rather than the more typical 18 - 21 nucleotide sequences that comprise Isis' other drugs, an attribute that reduces the cost of manufacturing.
ABOUT
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 19 drugs
in development. Isis' drug development programs are focused on treating
cardiovascular and metabolic diseases. Isis' partners are developing
antisense drugs invented by Isis to treat a wide variety of diseases. Isis is
a joint owner of
This press release includes forward-looking statements regarding Isis'
discovery and development of drugs for metabolic diseases, and the potential
of the antisense drug ISIS-SGLT2Rx to treat 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, including those statements that are described as Isis'
goals. 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
In this press release, unless the context requires otherwise, "Isis,"
"Company," "we," "our," and "us" refers to
SOURCEIsis Pharmaceuticals, Inc. -0-02/05/2009 /CONTACT: Kristina Lemonidis, Director, Investor Relations, +1-760-603-2490, orAmy Blackley , Ph.D., Assistant Director, Corporate Communications, +1-760-603-2772, both ofIsis Pharmaceuticals, Inc. / /Web Site: http://www.isispharm.com / (ISIS) CO:Isis Pharmaceuticals, Inc. ST:California IN: HEA MTC PHA BIO SU: TRI PR -- LA66986 -- 013602/05/2009 07:00 EST http://www.prnewswire.com