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Relevant comparators
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| One submitted trial (HELIOS-A) and an NMA support the comparable efficacy of vutrisiran and patisiran in patients with hATTR-PN. Alnylam is the market authorization holder for both Amvuttra (vutrisiran) and Onpattro (patisiran); advising that vutrisiran (SC every 3 months) is expected to replace patisiran (IV every 3 weeks) as the “standard of care” for hATTR-PN in Canada. Tegsedi (inotersen) is also a relevant comparator that was indicated by Health Canada for the treatment of hATTR-PN; its CADTH reimbursement criteria (December 2019) are identical to those of patisiran (July 2019). | Comment from the drug programs to inform CDEC deliberations. |
| Patisiran and inotersen are both reimbursed in the majority, but not all federal, provincial, and territorial jurisdictions. | Comment from the drug plans to inform CDEC deliberations. |
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Considerations for initiation of therapy
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| The key inclusion and exclusion criteria for the HELIOS-A (vutrisiran) and APOLLO (patisiran) trials are the same. The CADTH reimbursement criteria for patisiran and inotersen are also same. Consider alignment with the initiation criteria for patisiran and inotersen, if appropriate. Are there any additional patient characteristics beyond disease diagnosis, scoring, or staging that should be considered for eligibility criteria for vutrisiran? | CDEC agreed with the clinical expert that the eligibility criteria of patisiran should also apply to vutrisiran. The clinical expert did not identify a rationale for applying additional or modified eligibility criteria to patisiran. |
| The pre-NOC indication and reimbursement request for vutrisiran is: For the treatment of hATTR amyloidosis in adults. The submitted trial (HELIOS-A) only evaluated vutrisiran for hATTR-PN. Given the heterogeneous nature of the disease, there is potential for vutrisiran to be used more broadly, including for patients with cardiomyopathy. Are there other patient subtypes that should be assessed for eligibility for vutrisiran, such as patients with: 1. hATTR cardiomyopathy 2. a confirmed genetic mutation but presymptomatic (patients in the HELIOS-A trial had FAP stage I and II disease at baseline) 3. advanced polyneuropathy (the HELIOS-A trial did not include any patients with FAP stage III disease at baseline) or previous liver transplant. | An NOC for vutrisiran was issued on October 18, 2023, with the following indication: AMVUTTRA (vutrisiran injection) is indicated for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hATTR amyloidosis. The sponsor updated their request for reimbursement to be per indication. The clinical expert suggested that evidence of efficacy of vutrisiran has limited generalizability to the following patient populations: those with cardiomyopathy those with advanced-stage polyneuropathies those who have received a liver transplant those with a confirmed genetic mutation who are presymptomatic.
CDEC agreed with the clinical expert that there is no evidence to support the use of vutrisiran in these patients. |
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Considerations for continuation or renewal of therapy
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| The primary end point in the HELIOS-A trial was the mNIS+7. In 2019, the clinical experts consulted for the CADTH reviews of patisiran and inotersen advised that the mNIS+7 is not used in clinical practice to monitor patients and that some components (i.e., quantitative sensory testing) are not available in all centres. There are no clearly defined renewal criteria for patisiran and inotersen. What objective measures can be employed to assess the efficacy of vutrisiran over time, ensuring ongoing reimbursement? | CDEC agreed with the clinical expert who suggested that similar approaches as the ones already in place for patients on patisiran should be implemented. |
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Considerations for discontinuation of therapy
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| The discontinuation criteria for patisiran and inotersen include being permanently bedridden and dependent on assistance for basic activities of daily living or receiving end-of-life care. Consider alignment with the discontinuation criteria for patisiran and inotersen, if appropriate. Are there additional parameters that can be used to define loss of response, absence of clinical benefit, or disease progression specific to vutrisiran? | CDEC agreed with the clinical expert who suggested that similar discontinuation as the ones already in place for patients on patisiran criteria should be implemented. |
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Considerations for prescribing of therapy
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The product monograph notes that vutrisiran should be administered by a health care professional. There may be limited access to specialists with experience in the diagnosis and management of hATTR in some jurisdictions.Is there evidence supporting the combination use of vutrisiran with other RNA-targeted treatments like inotersen or TTR stabilizers such as tafamidis for ATTR amyloidosis cardiomyopathy or diflunisal (i.e., off-label use)? Should patients who are already on another RNA-targeted treatment or TTR stabilizer be eligible for treatment with vutrisiran?
| The clinical expert noted that no current evidence exists to support the combination use of vutrisiran with other RNA-targeted treatments or TTR stabilizers. CDEC agreed with the clinical expert that it would be unlikely that such combination of treatments would be used. |
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Generalizability
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| There is the potential for patients currently receiving patisiran (possibly inotersen) to be switched to vutrisiran. Is it appropriate for patients currently receiving patisiran (or possibly inotersen) to switch to vutrisiran? | CDEC agree with the clinical expert who did not anticipate any issues switching patients who were receiving patisiran (or possibly inotersen) to vutrisiran. |
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Care provision issues
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| The product monograph notes that vutrisiran should be administered by a health care professional. The sponsor has indicated that vutrisiran will be imported, distributed, and administered through Innomar Strategies. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is advised. Genetic testing is required to confirm a diagnosis of hATTR amyloidosis and differentiate it from other causes of amyloidosis. Beyond administration by health care professionals, are there any additional concerns regarding the preparation, storage, administration, or dispensing of vutrisiran? | The clinical expert noted that while some patients may have a preference for infusions by health care professionals, most will likely be able to perform self-administration of SC vutrisiran or receive support from a family member to do so. CDEC agree with the clinical expert. |
| Regarding vitamin A supplementation due to reduced serum vitamin A levels caused by vutrisiran, are there specific recommendations or considerations for its administration? | CDEC agreed with the clinical expert who identified no additional recommendations beyond those implemented with patisiran. |
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System and economic issues
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| Vutrisiran costs $143,041 per prefilled syringe. The sponsor’s BIA indicates that vutrisiran is anticipated to be associated with a cost of $173 million over the 3-year forecast horizon; a net budget increase of $24 million over 3 years vs. the current scenario (patisiran and inotersen only). | Comment from the drug plans to inform CDEC deliberations. |
| Patisiran and inotersen have successfully completed price negotiations for hATTR-PN. Alnylam is the market authorization holder for patisiran — and is aware of its negotiated price. | Comment from the drug plans to inform CDEC deliberations. |
