Isis Pharmaceuticals Announces Initiation of an Investigator-Sponsored Phase 2 Study of ISIS-TTR Rx in Patients with TTR Cardiomyopathy Amyloidosis

CARLSBAD, Calif., Isis Pharmaceuticals, Inc. announced today the initiation of an investigator-sponsored, open-label Phase 2 study evaluating ISIS-TTR_Rx in patients with wild-type transthyretin amyloidosis (wt-TTR amyloidosis, previously referred to as senile systemic amyloidosis, or SSA).  The Phase 2 study will be conducted by Dr. Rodney Falk, the director of the Cardiac Amyloidosis Program and a cardiovascular medicine specialist at the Brigham and Women's Hospital inBoston.

"Together with GSK, we are conducting a robust development plan designed to establish ISIS-TTR_Rx as a best-in-class treatment for all patients with TTR amyloidosis.  Already, we have demonstrated that ISIS-TTR_Rx, given as one, once a week, self-administered, at home injection, can robustly reduce TTR levels in patients with both the polyneuropathy and cardiomyopathy forms of the disease, and we have preliminary evidence of disease stabilization in patients with TTR-related cardiomyopathy," said Brett Monia, Ph.D., senior vice president of drug discovery and franchise leader for oncology and rare diseases at Isis Pharmaceuticals.  "Dr. Falk is a leading expert in TTR amyloidosis and has extensive knowledge of wt-TTR cardiomyopathy.  As such, Dr. Falk is an ideal physician to evaluate the effects of ISIS-TTR_Rx in these patients, who have the same type of disease as those who are represented in his large natural history database."

The Phase 2, investigator-initiated study will evaluate treatment with ISIS-TTR_Rx in approximately 50 patients with wt-TTR amyloidosis.  Patients must have evidence of cardiac disease as indicated by an interventricular septum thickness (IVS) of >1.3cm with a positive cardiac biopsy.  The effects of ISIS-TTR_Rx on cardiac disease stabilization will be measured by cardiac imaging at 6, 12 and 18 months.  Data from this study will provide additional information on ISIS-TTR_Rx and can also be included in the robust data package Isis and GSK are generating to support regulatory filings for ISIS-TTR_Rx in all patients with TTR amyloidosis.  For further study information, please visit www.clinicaltrials.gov and search for ISIS-TTR_Rx.

In addition to the Phase 2 study initiated today, ISIS-TTR_Rx is being evaluated in the following studies:

Isis is evaluating ISIS-TTR_Rx in a Phase 3 randomized, double-blind, placebo-controlled, international study (NEURO-TTR) 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.

Isis is evaluating ISIS-TTR_Rx in an open-label extension study that is eligible to patients with FAP who have completed the NEURO-TTR Phase 3 study. To date, all eligible patients have enrolled in the open-label extension study.

GSK plans to initiate a small Phase 3 study evaluating ISIS-TTR_Rx in patients with FAP in Japan.  

GSK plans to initiate a Phase 3 randomized, double-blind, placebo-controlled, multicenter, international study (CARDIO-TTR) in patients with familial amyloid cardiomyopathy (FAC) and wt-TTR amyloidosis who also have a history of heart failure. The study will measure the effects of ISIS-TTR_Rx on a clinical composite outcome that includes mortality, cardiac transplant and cardiovascular hospitalization.

Dr. Merrill D. Benson, professor of pathology and lab medicine and molecular genetics at Indiana University School of Medicine, is evaluating ISIS-TTR_Rx in an open-label, investigator-sponsored, Phase 2 study in patients with TTR amyloid cardiomyopathy, which includes patients with FAC and patients with wt-TTR amyloidosis.

Source: Isis Pharmaceuticals, Inc.