The transthyretin stabiliser tafamidis (brand name Vyndaqel) has been recommended in final draft guidance by the National Institute for Health and Care Excellence (NICE) for the treatment of transthyretin amyloidosis cardiomyopathy (ATTR-CM).
The indication includes adults with hereditary or wild-type (non-hereditary) ATTR-CM and this is the first ever approved treatment for this cohort of patients, with previous treatment options focusing on symptom management and supportive care.
Following its approval and final draft guidance from NICE, the once-a-day capsule is now available on the NHS, which is also thanks to interim funding from the Innovative Medicines Fund. It is hoped that around 1,500 people in England may benefit from the new treatment.
Tafamidis has been available on the NHS in Scotland since November 2023.
Commenting on the potential for tafamidis to improve patients’ quality of life, Professor Simon Ray, national clinical director for heart disease at NHS England, said: ‘A first of its kind, tafamidis will give those living with this rare progressive condition new hope – with NHS patients now able to benefit from a once-a-day treatment that can reduce the risk of hospitalisation and heart failure.’
Safety and efficacy of tafamidis
The NICE approval of tafamidis was based on the results of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) pivotal study and the ongoing ATTR-ACT LTE extension study.
ATTR-ACT was a 30-month, phase 3 double-blind randomised controlled trial evaluating how effective, safe and tolerable tafamidis was compared with placebo in adults with wild-type or hereditary ATTR-CM.
The researchers found tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalisations, with a relative risk ratio of 0.68 (0.48 per year vs 0.70 per year; 95% CI, 0.56 to 0.81).
At month 30, tafamidis was also associated with a lower rate of decline in distance for the six-minute walk test (P<0.001) and a lower rate of decline in Kansas City Cardiomyopathy Questionnaire–Overall Summary score (P<0.001).
The incidence and types of adverse events were similar in the two groups.
In the ATTR-ACT LTE trial, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo at a median follow-up of approximately 58 months.
There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44–0.79]; P<0.001).
The authors said this highlighted the importance of early diagnosis and treatment in ATTR-CM but added that ‘all patients with transthyretin amyloid cardiomyopathy could benefit from treatment with tafamidis‘.
In 2019, NICE published final guidance for inotersen for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis.
