Updated Evaluation of the Safety, Efficacy and Tolerability of Tafamidis in the Treatment of Hereditary Transthyretin Amyloid Polyneuropathy

Figures & data

Table 1 Summary of Tafamidis Clinical Trials and Open-Label Extension Studies

Clinical Trials	Study Design	Study Population	Primary Endpoints	Adverse Events	Outcomes
Fx-005^Citation17	Phase II/III Randomized, placebo-controlled double-blind trial Treatment: Tafamidis 20 mg once a day for 18 months	128 patients with documented V30M mutation and biopsy-confirmed amyloid deposits	NIS-LL Norfolk QOL-DN	AEs and SAEs incidence was similar in both groups Most frequent AE in tafamidis group was urinary tract infection	EE population: NIS-LL responders: 60% in tafamidis group versus 38.1% in placebo group (p=0.041). Norfolk QOL-DN change from baseline: 0.1 in tafamidis group versus 8.9 in placebo group (p=0.045).
Fx-006^Citation18	Single-arm open-label extension study of Fx-005 Treatment: Tafamidis 20 mg once a day for 12 months	86 patients with documented V30M mutation and biopsy-confirmed amyloid deposits	NIS-LL Norfolk QOL-DN	No additional adverse events	Sustained beneficial effect of tafamidis after 30 months of treatment. Patients who switched from placebo to treatment arm had slowing of disease progression Early treatment was associated with better outcomes.
Fx1A-201^Citation20	Phase II, open-label, single-arm study Treatment: Tafamidis 20 mg once a day for 12 months	19 ATTRv patients excluding V30M and V122I mutations	TTR stabilization at 6 weeks	Most common reported AEs: Falls (24%), diarrhoea (24%), extremity pain (19%)	TTR stabilization at Week 6 was achieved in 18 patients (94.7%).
Fx-1006A^Citation19,Citation22	Phase III, open-label extension study Treatment: Tafamidis 20 mg once a day for up to 10 years	Patients from Fx-005, Fx-006 (75 patients) and Fx1A-201 (18 patients) trials	NIS-LL Norfolk QOL-DN Death	No additional adverse events No deaths were considered related to tafamidis	Fx1A-303 – interim analysis up to 6 years: - All patients developed in some degree disease progression. - Rate of disease progression was similar in patients from P-T and T-T groups. - Less neurologic deterioration was seen in patients who were treated earlier with tafamidis. Survival analysis up to 8.5 years - 85% of V30M patients and 75% of non-V30M patients were alive at 9 and 8 years, respectively.
Japanese trial^Citation21	Single-arm, open-label multicentre study Treatment: Tafamidis 20 mg once a day for up to 3 years	10 Japanese ATTRv V30M and non-V30M patients with biopsy-confirmed amyloid deposits	TTR stabilization at 8 weeks	Most common reported AEs: nasopharyngitis and muscle weakness	All patients achieved TTR stabilization at 8 weeks.

Abbreviations: AE, adverse event; ATTRv, hereditary amyloid transthyretin amyloidosis; EE, efficacy-evaluable; NIS-LL, Neuropathy Impairment Score in the Lower Limbs; Norfolk QOL-DN, Norfolk Quality of Life-Diabetic Neuropathy questionnaire; SAE, serious adverse event; TTR, transthyretin; P-T, Placebo-Tafamidis; T-T, Tafamidis-Tafamidis.

Figure 1 Intent-to-treat slope analysis of (A) NIS-LL total score, (B) NIS-LL muscle weakness, and (C) Norfolk QOL-DN in patients with Val30Met ATTRv-PN (data from Fx-005, Fx-006 and Fx1A-201).^17,18,20 Slopes are adjusted at mean baseline value of the two treatment groups.

Note: Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years” by Fabio A. Barroso, Daniel P. Judge, Ben Ebede, Huihua Li, Michelle Stewart, Leslie Amass & Marla B. Sultan © 2017 The Author(s) taken from Amyloid (2017), Vol 24:3, copyright © Informa UK Limited, trading as Taylor & Francis Group (2017), reprinted by permission of the publisher.¹⁹

Abbreviations: NIS-LL, Neuropathy Impairment Score in the Lower Limbs; QOL-DN TQOL, Quality of Life-Diabetic Neuropathy total quality of life.

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