Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today results from a Phase 1 study with ISIS-TTRRx. The results demonstrated that treatment with ISIS-TTRRx produced dose-dependent statistically significant reductions of greater than 80 percent in transthyretin (TTR) protein. In this study, ISIS-TTRRx was generally well tolerated with no significant adverse events. ISIS-TTRRx is an antisense drug in development with GlaxoSmithKline (GSK) for the treatment of TTR amyloidosis, a severe and rare genetic disease characterized by progressive dysfunction of peripheral nerve and/or heart tissues. Isis and GSK are planning to begin a clinical study on ISIS-TTRRx this year designed to achieve an efficient route to registration.
"TTR amyloidosis is a fatal disease that affects approximately 50,000 patients worldwide. Patients with familial amyloid polyneuropathy, or FAP, experience TTR build up in their peripheral nerves and experience the loss of motor functions, such as walking. These patients also experience the accumulation of TTR amyloid in the heart, causing familial amyloid cardiomyopathy (FAC), and in their intestinal tract, which prevents the proper absorption of nutrients, leading to death. Since current treatments are highly limited, there is a great need to develop a drug that can reduce TTR levels thereby preventing, and potentially reversing, progression of this disease," said Merrill D. Benson, M.D., Professor of Medical Genetics at Indiana University.
"Currently the most effective way to retard progression of FAP is a liver transplant. However, many patients with FAP are unable to receive a liver transplant due to availability of a donor liver or the patient's diminished health. In the small number of patients who do receive a transplant, their quality of life is substantially compromised. Although, liver transplant replaces mutant TTR, amyloid formation continues due to accumulation of normal TTR protein," said Richard Geary, Ph.D., Senior Vice President of Development at Isis. "ISIS-TTRRx blocks the production of both normal and mutant TTR, thereby preventing further amyloid accumulation, which may prevent, and potentially reverse, disease progression."
The Phase 1 study of ISIS-TTRRx was a blinded, randomized, placebo-controlled, dose-escalation study designed to assess the safety and pharmacokinetic profile of ISIS-TTRRx in healthy volunteers. ISIS-TTRRx was evaluated in single and multiple doses ranging from 50 mg per week up to 400 mg per week. After only four weeks of dosing, subjects in the 200 mg and 400 mg multiple-dose cohorts displayed a mean reduction of 44 percent and 81 percent in TTR levels, respectively. ISIS-TTRRx was generally well tolerated in all subjects.
"In this study, we observed substantial dose-dependent reductions in TTR protein of greater than 80 percent. Based on the mechanism of action and the early data we have presented, we believe that ISIS-TTRRx could provide benefit to patients with FAP," said Brett Monia, Ph.D., Senior Vice President, Drug Discovery and Corporate Development of Isis. "Together with our partner GSK, we are finalizing the development plan for ISIS-TTRRx, which is intended to achieve an efficient route to registration. Our next clinical study for ISIS-TTRRx will begin in 2012 and evaluate the effects of the drug on disease progression and other measures of disease burden/improvements on quality of life in patients with FAP."
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