Isis Pharmaceuticals announces addition of two new drugs to development pipeline

Isis Pharmaceuticals, Inc. announced today that it has added two new drugs to its development pipeline, ISIS-FGFR4Rx and ISIS-STAT3Rx.  

ISIS-FGFR4Rx is designed to treat obesity by increasing metabolism, particularly by increasing lipid and fat burning.  ISIS-FGFR4Rx specifically blocks the production of fibroblast growth factor receptor 4 (FGFR4) in the liver and fat tissue. In addition, ISIS-FGFR4Rx should not reduce FGFR4 expression in the central nervous system (CNS) or heart, thereby avoiding the CNS and cardiovascular side effects associated with many obesity drugs in development.  In preclinical studies, inhibition of FGFR4 lowered body weight and enhanced weight loss when administered as a single agent, in combination with a caloric-restricted diet and in combination with an appetite-suppressing drug and a caloric-restricted diet.  The reduction in body weight was accompanied by an improvement in insulin sensitivity. ISIS-FGFR4Rx was safe and well tolerated in multiple species.  ISIS-FGFR4Rx is the first drug in Isis' metabolic franchise to treat obesity.  

"Obesity has become an epidemic.  It is a condition that increases the risk of diabetes, heart disease, stroke, arthritis and some cancers, and an area where most centrally acting drugs have failed due to side-effects.  Consequently, our peripherally acting drugs such as ISIS-FGFR4Rx could have significant therapeutic benefit without the associated central nervous system toxicities that plague many other anti-obesity drugs.  Our ability to selectively target FGFR4 in only the tissues where FGFR4 plays an important role in modulating body weight, makes it an ideal target for our antisense technology," said Sanjay Bhanot, M.D., Ph.D., Vice President, Metabolic Disorders and Head of Translational Medicine at Isis Pharmaceuticals.  "In our preclinical studies, we observed reductions in body fat, reversal of existing obesity and improved insulin sensitivity with ISIS-FGFR4Rx, making this a promising drug with an exciting therapeutic profile."

ISIS-STAT3Rx is designed to treat cancer by inhibiting the production of a gene critical for tumor cell growth and survival.  Signal transducer and activator of transcription 3 (STAT3) is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma and promotes tumor cell growth and prevents cell death.  In preclinical studies, ISIS-STAT3Rx demonstrated antitumor activity in animal models of human cancer with an attractive safety profile.  ISIS-STAT3Rx will be evaluated in a variety of cancers where STAT3 is believed to play a key role such as liver cancers and multiple myeloma.

"Cancer is a therapeutic area in which we believe antisense drugs could have a profound treatment impact.  STAT3 is a target that is widely viewed as promising, but it is inaccessible to traditional drug approaches due to the nature of the protein and its function in the cell," said Brett P. Monia, Ph.D., Vice President, Drug Discovery and Corporate Development.  "ISIS-STAT3Rx adds to our already broad and mature cancer franchise consisting of a Phase 3 drug and three Phase 2 drugs, each with promising clinical data.  These drugs inhibit many of the processes that tumor cells use to grow, proliferate, and metastasize."