Tafamidis: Approval denotes proven added benefit
Tafamidis meglumine (trade name: Vyndaqel) was approved in November 2011 for the treatment of transthyretin amyloidosis in adults. This rare disorder ("orphan disease") is caused by a defective gene and is associated with progressive nerve damage (neurological degeneration) that tafamidis is supposed to delay. According to § 35a SGB (Social Code Book) V, an added benefit is regarded as proven if a drug for a rare disease - known as an orphan drug - has been approved. The German Institute for Quality and Efficiency in Health Care (IQWiG) has assessed tafamidis at the request of the Federal Joint Committee (G-BA).
The scientific assessment by IQWiG has produced a hint of a positive effect of tafamidis on neurological degeneration.
Tafamidis compared with "best supportive care"
Transthyretin (TTR) is formed in the liver and is involved in the transport of the thyroid hormone, thyroxine. Mutations in the TTR gene can lead to transthyretin amyloidosis in which there is a build-up of an abnormally modified protein in various organs. These insoluble deposits result in a chronic disease that is associated with the progressive degeneration of the nervous system (polyneuropathy). In most patients, the transthyretin gene is modified at a particular site and this mutation is called "Val30Met". Tafamidis meglumine is approved for the treatment of transthyretin amyloidosis in adult patients with stage 1 neurological disorders to delay the progression of degeneration of peripheral nerves, e.g. in the arms and legs.
Treatment with tafamidis combined with "best supportive care" was compared with "best supportive care" alone. The term "best supportive care" means the therapy that provides the patient with the best possible individually optimized supportive treatment to alleviate symptoms and improve the quality of life, for instance the treatment of pain in polyneuropathy with other drugs (e.g. amitriptyline, gabapentin).
Positive effect in neurological disorders only limited
Only one of the two relevant studies (Fx-005) provided reliable data - and only for patients with a particular genetic defect (Val30Met). The second study (Fx1A-201) in adults with different genetic defects was not controlled, i.e. here the effect of tafamidis was not directly compared with another treatment. It remains unclear how the results of the reliable study can be applied to the patients with genetic defects other than Val30Met.
Assessment of the study data according to the methods of IQWiG produced a hint of a positive effect of tafamidis in respect of the progression of nerve damage. However the effect was only minor.
With regard to other patient-relevant outcomes (other symptoms and side effects, mortality, quality of life), the Institute was unable to identify any further statistically significant advantages or disadvantages of tafamidis compared with the comparator treatment.
G-BA decides on the extent of added benefit
The dossier assessment is part of the overall procedure for early benefit assessment conducted by the G-BA. After publication of the manufacturer's dossier and its assessment by IQWiG, the G-BA initiates a formal commenting procedure which provides further information and can result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.