ISIS Pharmaceuticals Reports Data from ISIS-TTR Rx in patients with Transthyretin Amyloid-Related Cardiomyopathy

Up to 88 percent reduction in transthyretin protein in patients with TTR-related cardiomyopathy observed

CARLSBAD, Calif., Isis Pharmaceuticals, Inc. announced today encouraging preliminary results from an investigator-sponsored study in patients with transthyretin amyloid-related cardiomyopathy that was presented yesterday by Dr. Merrill Benson at the 20th World Congress on Heart Disease (WCHD) in Vancouver, Canada.

"I am encouraged by the safety, tolerability, TTR lowering and apparent stabilization of cardiac disease progression we have observed in the study to date," said Merrill Benson, M.D., professor of pathology and medical genetics at Indiana University.  "In this open-label study, measures of TTR amyloid cardiac disease, including echocardiographic and strain imaging evaluation, indicated little to no cardiac disease progression after six months of dosing with ISIS-TTR_Rx. These data compare favorably to our previously published work, which showed that patients with TTR-related cardiomyopathy exhibit disease progression at six months using similar echocardiographic measurements." 

"These new data on cardiac measures in patients with TTR-cardiomyopathy give us additional confidence that the TTR-lowering we have observed in this and other clinical studies has the potential to provide therapeutic benefit to patients with TTR amyloidosis," said Brett Monia, Ph.D., senior vice president of drug discovery at Isis Pharmaceuticals.   

In a presentation titled, "Transthyretin Amyloid Cardiomyopathy Treatment with an Antisense Oligonucleotide Inhibitor of TTR (ISIS-TTR_Rx)", Dr. Benson reported on preliminary results from his investigator-sponsored open-label study in patients with TTR-related cardiomyopathy.  In patients who completed nine months of weekly dosing (n=3) with 300 mg of ISIS-TTR_Rx, reductions in TTR protein of up to 88% were observed with a mean reduction of 78%.  In addition, patients who completed six months of dosing (n=5) were evaluated by echocardiography and showed no increase in left ventricular wall thickness.  In this study, patients receive 300 mg of ISIS-TTR_Rx once weekly for a total of 24 months with a three month follow up period.  

ABOUT ISIS-TTR_Rx 
ISIS-TTR_Rx is a gen 2.0+ antisense drug Isis is developing with GSK for the treatment of TTR amyloidosis.  ISIS-TTR_Rx is administered as a once weekly subcutaneous injection and is designed to inhibit the production of all forms of TTR protein, including both mutant and wild type, offering a unique approach to treat all types of TTR amyloidosis. 

ISIS-TTR_Rx is currently being evaluated in a Phase 3 randomized, double-blind, placebo-controlled, international study in patients with familial amyloid polyneuropathy (FAP). The study is designed to support an application for marketing approval of ISIS-TTR_Rx in patients with FAP.  The fifteen month study will measure the effects of ISIS-TTR_Rx on neurological dysfunction and on quality-of-life.  For further study information, please visit www.clinicaltrials.gov and search for the identifier number NCT01737398.   

ABOUT TTR AMYLOIDOSIS
TTR amyloidosis is a severe and fatal disease in which patients with TTR amyloidosis experience TTR build up in major organs, including peripheral nerves, heart, intestinal tract, kidney and bladder.  Patients with TTR-related cardiomyopathy experience ongoing debilitating heart damage resulting in progressive heart failure.  Therapeutic options for the treatment of TTR-related cardiomyopathy are very limited and there are currently no drugs approved for the treatment of TTR-related cardiomyopathy. 

Source: Isis Pharmaceuticals, Inc.