Tafamidis Delays Disease Progression in Patients with Transthyretin Amyloid Polyneuropathy, Pfizer Study Suggests

An interim analysis of the Phase 3 trial for tafamidis (Fx-1006A) as a therapy for patients with hereditary transthyretin amyloid polyneuropathy (TTR-FAP) shows the investigational treatment delays disease progression, Pfizer announced.

The study, “Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years,” was published in the journal Amyloid: The Journal of Protein Folding Disorders.

The analysis is part of an ongoing study (NCT00925002) to evaluate the long-term safety and effectiveness of tafamidis in 93 patients with TTR-FAP who already had received the medication in previous trials. The interim analysis included 75 patients with the most common TTR-FAP mutation, Val30Met, and 18 non-Val30Met patients.

Among patients with Val30Met, 38 had taken the medication for 18 months in a randomized trial. After the study’s completion, they continued on the medication for 12 months as part of an open-label extension study. The remaining patients were randomized to a placebo during the 18-month trial and then switched to tafamidis at the start of the 12-month extension study. After completing the extension study, both groups began the ongoing, long-term study.

The interim analysis suggests that patients treated with tafamidis from the beginning of the 18-month period showed decreases in disease progression by the 66th month. Patients on tafamidis also were less prone to advance to more debilitating stages of the disease, such as the need to use a wheelchair, when compared with patients who were randomized to the placebo during the same period.

Three tests were used to assess disease progression: the Neuropathy Impairment Score for Lower Limbs (NIS-LL), a subscale of the NIS-LL that measures muscle weakness, and a measure of total quality of life (TQOL).

Researchers found that over time, the rates of worsening NIS-LL, NIS-LL muscle weakness, and TQOL were less in patients treated with tafamidis at the beginning of the trial compared with the placebo-treated patients. Even when introduced to patients during the open-label extension only, tafamidis was seen to slow the worsening rates to a level comparable to the rates of patients who took the medication early on.

In patients with non-Val30Met mutations who previously completed a 12-month, open-label study, researchers detected some worsening in the rates of disease progression, including NIS-LL. However, because researchers lacked a control group for non-Val30Met patients, interpretation of these results is limited.

Overall, tafamidis was well-tolerated and had no unexpected safety issues, the study said. Adverse effects were detected in 10% or more of the patients and included urinary tract infection, falls, thermal burns, influenza, headaches, and upper respiratory tract infection. Serious adverse effects were detected in 2% or more of patients and included cardiac failure and chest pain, sepsis, urinary tract infection, and transient ischemic attacks.

Tafamidis is an approved therapy for TTR-FAP in 40 countries for adult patients with early-stage symptomatic polyneuropathy and is sold under the brand name Vyndaqel. It is not approved in the United States.

“This is a life-long disease, so these findings are important because they suggest that tafamidis not only provided a sustained disease-modifying effect, it also was generally well tolerated over the long term,” Fabio Barroso, MD, the study’s lead author and a neurologist at the Raul Carrea Institute for Neurological Research in Buenos Aires, Argentina, said in a press release. “These results offer hope for people with TTR-FAP, many of whom have witnessed family members and loved ones suffer from this relentless, progressive, and fatal disease.”

Pfizer is the only sponsor of the Transthyretin Amyloidosis Outcomes Survey (THAOS), the largest database of TTR amyloidosis cases, and is leading initiatives to raise awareness for TTR amyloidosis among clinicians.

“The analysis is the longest prospective evaluation to date of any medicine being studied for TTR-FAP and builds on previous studies suggesting tafamidis provides benefit when given early in the disease and is associated with delay in disease progression over the long term,” said Kevin W. Williams, chief medical officer at Pfizer Innovative Health Rare Disease. “Evaluating potential therapies for the treatment of rare diseases that have limited to no treatment options, such as TTR-FAP, is critical, and Pfizer Rare Disease is pleased that these findings help us to better understand the long-term safety and efficacy in patients with this debilitating illness.”