Predictive model of response to tafamidis in hereditary ATTR polyneuropathy

Abstract

Conflict of interest: Conflict of interest statement: JWK discovered tafamidis at the Scripps Research Institute; is a shareholder of FoldRx (Pfizer), the companies that developed tafamidis into a drug; and he and ETP receive royalty payments from tafamidis sales. JWK is a paid consultant for the Pfizer Orphan and Rare Diseases organization. Pfizer supported JWK's expenses with travel and accommodation for scientific meetings. TC is a past and current investigator in clinical trials sponsored by FoldRx, Pfizer, Alnylam, Ionis, and Prothena; these trials were paid per protocol to Centro Hospitalar do Porto. TC is a consultant for Pfizer, Alnylam, Ionis, and Prothena. TC has spoken on behalf of Pfizer, Alnylam, Glaxo, and Prothena at scientific meetings and received financial compensation. Pfizer, Alnylam, Ionis, and Biogen supported TC's expenses with travel, accommodation, and registration for scientific meetings.

Blinded potency comparison of transthyretin kinetic stabilisers by subunit exchange in human plasma

“…It remains unclear what the minimal reduction in the rate of TTR tetramer dissociation is to achieve maximal clinical benefit, although TTR amyloidosis clinical trials and large clinical studies have put some constraints on this. We have previously reported data showing that slowing (36% of patients; n ¼ 76) or cessation of progression (34% of patients; n ¼ 72) has been observed in hereditary TTRV30M polyneuropathy (ATTRv-PN) with tafamidis treatment (20 mg QD) [42], a clinical result associated with a mean tafamidis plasma concentration in these patients after 12 months of dosing of % 9 mM. This concentration of tafamidis, assuming it is the same in ATTRwt-CM patients at the 20 mg QD dose, would be expected to slow the rate of TTRwt tetramer dissociation to $14% of normal based on the subunit exchange data presented herein.…”

Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience

“…As demonstrated previously [33], time to progression was also similar in our patients with either p.Val50Met or nonp.Val50Met variants. In one of the largest studies on tafamidis to date, Monteiro et al reported treatment outcomes in 210 patients for a follow-up period of 18 to 66 months [34]. In their study, 29.5% were categorised as non-responders and 36.2% as partial responders to treatment with tafamidis.…”

Clinical 3-D Gait Assessment of Patients With Polyneuropathy Associated With Hereditary Transthyretin Amyloidosis

“…It is interesting to note that the trend (increase or decrease) of the mean value for most gait parameters is inverted when comparing the AC-SPS pair to the SPS-SPSL pair (when the mean value is higher for SPS than AC, it is lower for SPSL than SPS, and vice versa). This finding may be explained by the reported effect of protection of disease progression on the first years of earlystage treatment with tafamidis (most of the patients in the SPS group take this medication), in contrast to its use at a later time as well as in later-stage patients when it is less effective (36)(37)(38).…”