Table 1.
Summary of Tafamidis Clinical Trials and Open-Label Extension Studies
| Clinical Trials | Study Design | Study Population | Primary Endpoints | Adverse Events | Outcomes |
|---|---|---|---|---|---|
| Fx-00517 | 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-00618 | 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-20120 | 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-1006A19,22 | 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 trial21 | 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.