Pfizer’s Vyndaqel (tafamidis) can significantly delay the progression of familial amyloid polyneuropathy, regardless of its severity before treatment or which mutation causes it, a study reports.
The research, based on the combined results of two clinical trials, appeared in the European Journal of Neurology. The title of the article is “Tafamidis delays neurologic progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy.”
Familial amyloid polyneuropathy, or FAP, is a rare genetic disease caused by TTR gene mutations. The abnormalities lead to the formation of amyloid fibers that damage both organs and periphery nerve cells — those outside the brain and spinal cord.
The symptoms of the neurodegenerative disease and its progression depend on the mutation a patient has. The most common mutation is the amino acid substitution Val30Met. Patients with non-Val30Met mutations have poorer outcomes, doctors have found.
Vyndaqel stabilizes the TTR gene’s production of TTR protein, preventing the formation of the potentially toxic fibers.
The only approved medicine that can significantly delay the nerve cell damage in FAP, Vyndaqel has become the standard treatment for the disease in Europe, parts of Asia, and Latin America. The U.S. Food and Drug Administration continues to weigh whether to approve it.
Several clinical trials have focused on Vyndaqel’s ability to treat FAP, particularly in patients with a TTR Val30Met mutation. But researchers have failed to offer a definitive conclusion on whether the treatment can help patients with non-Val30Met mutations.
One of the trials in the pooled-results analysis — a 12-month Phase 2 study (NCT00630864) — looked at Vyndaqel’s ability to counter FAP stemming from non-Val30Met mutations. The results were mixed. The treatment promoted TTR protein stabilization but failed to help the 21 patients achieve significant neurological improvements, results showed.
In addition, the trial included no control group, making it harder to draw conclusions from the findings.
Seeking a better assessment, researchers decided to pool data from the Phase 2 trial and a placebo-controlled Phase 2/3 trial (NCT00409175) of 125 patients with a TTR Val30Met mutation.
The patients with non-Val30Met mutations were older, had had the disease longer, and had worse symptoms than the patients with the Val30Met mutation. Because of these differences between the groups, the researchers adjusted the findings to account for the severity of symptoms at the start of treatment.
They discovered that the adjusted neurological-function scores between the Val30Met and non-Val30Met patients were similar after 12 months of treatment. The progression of the disease was also similar between the groups. Both groups had much lower neurological impairment than the placebo group.
“This analysis demonstrated that treatment with tafamidis [Vyndaqel] delayed neurologic progression comparably in non-Val30Met and Val30Met patients,” the researchers reported.
A key takeaway from the research was that Val30Met and non-Val30Met patients may have nerve-cell damage progression trajectories that are more similar than scientists thought.