Rare Neurodegenerative Disease Drug Slows Progression in Phase 3 Trial


Vyndaqel in development for mild transthyretin familial amyloid polyneuropathy (TTR-FAP).

A post-hoc analysis involving data from 3 sequential studies revealed that long-term therapy with tafamidis (Vyndaqel) slowed the progression of mild transthyretin familial amyloid polyneuropathy (TTR-FAP).

TTR-FAP is a rare neurodegenerative disease that affects an estimated 10,000 worldwide. When the disease is left untreated, patients die at an average of within 10 years of symptom onset.

TTR-FAP is caused by a mutation in the protein transthyretin (TTR) called Val30Met, which results in the production of unstable TTR proteins that accumulate as amyloid deposits in nerves and other organs, and interferes with normal function.

In an analysis published in Amyloid: The Journal of Protein Folding Disorders, researchers found that over varying periods of up to 5.5 years, patients with the Val30Met mutation treated with Vyndaqel during the early stage of the disease had minimal neurological progression, and in preservation of body weight.

Vyndaqel is a novel specific transthyretin (TTR) stabilizer that is designed to prevent or slow the formation of abnormal TTR proteins and subsequent amyloid deposits. The findings were based on data from 3 studies: an 18-month, double-blind, placebo-controlled, randomized phase 3 pivotal trial with 125 patients with TTR-FAP; a 12-month open-label extension; and a second, ongoing, open-label, long-term extension study.

Researchers examined a subset of 71 randomized patients whose neurological impairment was defined as mild just before starting treatment with Vyndaqel, either at the start of the study for patients in the Vyndaqel group, or upon entry into the first open-label extension for patients in the placebo group.

Mild neurological impairment was defined as Neuropathy Impairment Score for Lower Limbs (NIS-LL) total score of 10 or less. The results of the study showed that in 31 patients at 5.5 years, treatment with Vyndaqel resulted in minimal neurologic disease progression; a mean change from baseline of 5.3 NIS-LL points, which translated to an annual rate of 1.0-point increase NIS-LL.

Treatment-induced adverse events were as follows: urinary tract infections; nasopharyngitis; influenza; diarrhea; headache and pain in an extremity; back pain; upper respiratory tract infection; depression and thermal burn; upper abdominal pain, anxiety, punctate keratitis, pharyngitis, decreased tear breakup time; and constipation, nausea, and vomiting.

“These findings underscore the long-term benefits of early intervention with Vyndaqel for symptomatic patients with TTR-FAP,” said Dr. Kevin W. Williams, chief medical officer of Rare Disease at Pfizer Innovative Health. “This analysis, which is based on the longest prospective evaluation to date of any medication being studied for TTR-FAP, provides health care professionals with important insights into the management of patients with this disease.”

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