AMVUTTRA (vutrisiran) - Amylose héréditaire à transthyrétine

Key points

Approval of reimbursement for the treatment of hereditary transthyretin amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. 

Therapeutic improvement?

No therapeutic improvement with respect to ONPATTRO (patisiran).

Role in therapeutic strategy?

Patients with hATTR amyloidosis with polyneuropathy require specialist care with regular follow-up by a multidisciplinary team (particularly including a neurologist, a cardiologist, and a geneticist). The treatment decision must be taken in coordination with FILMENUS network neuromuscular disease expert/reference centres.

The treatment of hATTR amyloidosis with polyneuropathy is currently based on:

• Symptomatic treatments of clinical manifestations of the disease (such as neurological, digestive, cardiac and ophthalmological manifestations) along with treatments of end-stage organ damage (such as end-stage heart or kidney failure);
• Specific anti-amyloid treatments for symptomatic patients.

Anti-amyloid treatments target the cause of the disease by preventing the formation of new amyloid deposits. To date, 3 anti-amyloid medicinal products have been granted marketing authorisation for the treatment of hATTR amyloidosis with polyneuropathy:

• ONPATTRO (patisiran), intravenous infusion: interfering RNA indicated for patients with stage 1 and 2 polyneuropathy.
• TEGSEDI (inotersen), subcutaneous injection once per week: antisense oligonucleotide indicated for stage 1 and 2 polyneuropathy in patients with hATTR amyloidosis.
• VYNDAQEL (tafamidis), per os: tetramer stabiliser indicated for patients with stage 1 polyneuropathy only.

Liver transplantation4 is a therapeutic option, for early-onset forms (< 50 years) with V30M mutation. Patients must have an estimated 5-year survival < 50% to benefit. The prognostic factors of poorer response to liver transplantation are late-onset forms (> 50 years), treatment at an advanced stage of the disease or poor nutritional status of patients.3,10 The aim of liver transplantation is to prevent new amyloid deposits by suppressing the main source of mutated TTR.

Despite transplantation, some patients may continue to experience progression insofar as it does not prevent mutated TTR production in the eye or wild-type TTR production in non-V30M or older V30M patients; this may contribute to the progression of clinical neurological, ocular and cardiac manifestations, even post-transplantation.

 Role of the medicinal product

Considering the lack of evidence of superiority of vutrisiran over patisiran, but only evidence of non-inferiority of vutrisiran versus patisiran on a biological ranked secondary outcome measure and the effect size of vutrisiran based on the evidence of superiority versus an external placebo group on the mean variation of the mNIS+7 score after 18 months of treatment outcome measure, in an open-label study, the proprietary medicinal product AMVUTTRA (vutrisiran) is a second-intent treatment, after the proprietary medicinal product ONPATTRO (patisiran) which remains the first-intent treatment, for the treatment of adult patients with hATTR amyloidosis with stage 1 or stage 2 polyneuropathy.

In the absence of comparative clinical studies versus other clinically relevant comparators, it is not possible to rank AMVUTTRA (vutrisiran) versus these drugs.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 25/04/2023. L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir le traitement de l’amylose héréditaire à transthyrétine (amylose hATTR) chez les patients adultes atteints de polyneuropathie de stade 1 ou de stade 2. 

L’efficience du produit n’est pas démontrée en raison des deux réserves méthodologiques majeures, portant sur l’estimation de l’efficacité du vutrisiran et sur la méthodologique utilisée pour mesure et valoriser la désutilité liée au mode d’admistration, qui invalident les résultats de l’évaluation économique.  

L’estimation de l’impact budgétaire associé à l’introduction du vutrisiran dans l’indication revendiquée n’est pas validée en raison de la réserve méthodologique majeure portant sur la modélisation.  

> AMVUTTRA - Avis économique (pdf°