Saturday, July 13, 2024

Transthyretin Amyloidosis Treatment Advanced: NICE Endorses Tafamidis for Cardiomyopathy

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Cardiomyopathy treatment with tafamidis is recommended within its marketing authorization for adults with wild-type or hereditary transthyretin amyloidosis (ATTR‑CM), provided Pfizer supplies it according to a commercial arrangement. This recommendation comes from the committee’s review, which highlighted the limited treatment options for transthyretin amyloidosis, a progressive condition leading to heart failure. Tafamidis is the first treatment aimed at addressing the condition directly, rather than merely managing symptoms.

ATTR‑CM is a severe and progressive condition that can result in heart failure. Current treatment options are limited to managing symptoms and providing supportive care. Tafamidis represents a significant breakthrough as the first treatment that targets the condition itself. Clinical trial evidence indicates that tafamidis can significantly reduce deaths and hospitalizations related to heart and blood vessel conditions compared to a placebo. However, uncertainties remain about the long-term survival and duration of treatment with tafamidis. Additional evidence from a different study helps to mitigate some of these uncertainties.

The economic analysis suggests that the cost-effectiveness of tafamidis falls within the range deemed acceptable by the National Institute for Health and Care Excellence (NICE) for the National Health Service (NHS) resource allocation. As a result, tafamidis is recommended for use. The efficacy and safety of tafamidis were evaluated in the LIBRETTO-001 (NCT03157128) trial, a multicenter, open-label, multi-cohort study involving 65 patients with RET fusion-positive thyroid cancer who were either systemic therapy-naïve or had been previously treated. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The trial found an ORR of 85% among previously treated patients and 96% among systemic therapy-naïve patients.

Efficacy, Cost-Effectiveness, and Safety Profile Highlighted by NICE

The median DOR was 26.7 months for previously treated patients and not evaluable for systemic therapy-naïve patients. Additional supportive evidence came from the LIBRETTO-121 study, which included 10 pediatric and young adult patients, showing an ORR of 60% with 83% maintaining a response for 12 months or more.

Common adverse reactions included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. Serious adverse events, though rare, included bacterial infections, skin necrosis, foreign body granulomas, acute poisoning reactions requiring intensive care, and drug urticaria reactions. The recommended dosage of tafamidis for pediatric patients aged 2 to less than 12 years is based on body surface area, while for those aged 12 years and older, it is based on weight. Detailed dosing information is available in the prescribing information.

The price of tafamidis is £10,685 for 30 capsules of 61 mg, excluding VAT. The company has arranged a discount for the NHS, although the size of this discount is confidential. The committee noted that there are currently no other disease-modifying treatments for transthyretin amyloidosis in England, underscoring the unmet need. The cost-effectiveness analysis considered several factors, including longer-term data from the ATTR‑ACT LTE trial, and concluded that the cost per quality-adjusted life year (QALY) gained was within the acceptable range of £20,000 to £30,000.

Transthyretin Amyloidosis

NICE Recognizes Tafamidis as Cost-Effective Treatment for Transthyretin Amyloidosis

ATTR‑CM is a debilitating condition affecting both physical and psychological well-being. It often leads to loss of mobility and independence, significantly impacting the quality of life for patients and their caregivers. Symptoms include shortness of breath, palpitations, abnormal heart rhythms, fatigue, and chest pain. The clinical experts highlighted that the condition is often diagnosed later in life and can be associated with considerable psychological and financial burdens.

The diagnostic pathway for transthyretin amyloidosis has evolved, with most diagnoses now made using medical imaging rather than biopsy, allowing for earlier detection. Despite improvements in diagnosis rates, the condition remains underdiagnosed. The appropriate comparator for tafamidis in clinical practice is best supportive care (BSC), as other potential comparators like diflunisal and SGLT2 inhibitors are either not well-tolerated or not part of established NHS practice for this condition.

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The committee recognized the substantial unmet need for disease-modifying treatments for transthyretin amyloidosis and concluded that tafamidis is a cost-effective option for the NHS. The ICER for tafamidis was within the acceptable range, and the committee recommended its use, emphasizing the importance of making it available to patients who need it. This decision requires integrated care boards, NHS England, and local authorities to comply with the recommendations within three months of publication. Tafamidis is also supported by Welsh ministers for implementation in the NHS in Wales within two months of the final guidance publication. This ensures that patients with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy can access tafamidis if deemed appropriate by their healthcare professional.


Resource: National Institute for Health and Care Excellence, June 19, 2024

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