Drug Reduces TTR Protein by 80 Pct: Isis Phase I Data
Isis and GlaxoSmithKline’s drug against TTR amyloidosis, a severe genetic disease that impairs peripheral nerve or heart tissue, has shown significant results in a Phase 1 study without serious side effects, Isis announced on Thursday.
The two companies are planning to begin a clinical study on the TTR amyloidosis treatment, ISIS-TTRRx, this year, which will bring them closer to approval.
"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, Senior Vice President of Development at Isis in a statement.
"ISIS-TTRRx blocks the production of both normal and mutant TTR, thereby preventing further amyloid accumulation, which may prevent, and potentially reverse, disease progression," Geary said.
The new treatment is an investigational drug designed to prevent the production of all forms of TTR, and may offer an alternative approach to treat all types of transthyretin-related amyloidosis.
The study of the new treatment was designed to evaluate the safety and pharmacokinetic profile of ISIS-TTRRx in healthy volunteers. Participants were given single or multiple doses ranging from 50 mg to 400 mg per week. After about a month, participants in the 200 mg and 400 mg multiple-dose groups showed an average reduction of 44 to 81 percent in TTR levels.
"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, Senior Vice President, Drug Discovery and Corporate Development of Isis in a statement.
“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," Monia said.
Transthyretin amyloidosis is a genetic disease in which a mutant gene produces a misfolded for of TTR that accumulates in tissues and disrupts their function. TTR builds up as fibrils in tissues in the heart, peripheral nerves, and gastrointestinal tract.
There are two common types of transthyretin amyloidosis, familial amyloid cardiomyopathy which affects more than 40,000 patients globally, and familial amyloid polyneuropathy which affects more than 10,000 patients worldwide.