The Institute for Clinical and Economic Review (ICER) has shared the details of its future analysis comparing the clinical benefits and long-term cost-effectiveness of approved Spinraza (nusinersen) and investigational therapy AVXS-101 for people with spinal muscular atrophy (SMA).
Now the institute has released a draft scoping document outlining its plans for the analysis, of which a final version is expected by January 2019.
The review will address uncertainties that remain regarding the therapeutic benefits of Spinraza and AVXS-101 compared with supportive care and with each other for SMA patients, as well as the cost-effectiveness of the treatments.
Effectiveness and safety data will be collected not only from randomized controlled trials, nonrandomized studies, and high-quality reviews, but also from patients, patient advocacy organizations, and the therapies’ manufacturers.
ICER will evaluate effectiveness based on mortality, the need for permanent invasive ventilatory support, motor function (through several validated tests), mobility, the presence of respiratory or gastrointestinal support and other complications associated with SMA, and quality of life.
To assess the safety of the therapies, the review will include the frequency of serious adverse events, treatment-associated adverse events, adverse events leading to discontinuation, and local reactions of Spinraza and AVXS-101.
ICER will also take into account other potential benefits of the two therapies to patients, caregivers, and the entire “infrastructure” of care.
The cost-effectiveness ratio of each treatment will be measured with ICER’s economic model, which will include direct medical costs related to therapy administration, monitoring, SMA-related care, and serious adverse events.
Results will be expressed in terms of the cost per life-year gained, per life-year gained adjusted to quality of life, and per specific clinical benefits. Whenever possible, the cost-effectiveness ratio will be calculated by SMA subtype, presymptomatic or symptomatic status, and age of disease onset.
ICER also plans to evaluate the potential budget impact of both therapies versus supportive care in the health system over a five-year period.
The institute encourages stakeholders, including clinical experts and patients, to provide input and suggest refinements to the scope, in this way ensuring all perspectives are adequately considered. Public comment submissions are open until Sept. 12 and can be submitted by email. ICER plans to release a revised draft scoping document around Sept. 19.
ICER’s Patient Participation Guide and Manufacturer Engagement Guide provide additional guidance for submitting public comments, including suggestions for what types of information may be most useful.
“This budgetary impact analysis will indicate the relation between treatment prices and level of use for a given potential budget impact and will allow assessment of any need for managing the cost of such interventions,” ICER wrote in the document.
The results will be reviewed during a March 2019 meeting of one of ICER’s three independent evidence appraisal committees.
SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene, which leads to a reduced production of the SMN protein. While a second survival motor neuron gene (SMN2) is also capable of producing SMN, only 10% of the protein it produces is fully functional.
Spinraza is the first and only disease-modifying treatment approved by the U.S. Food and Drug Administration for children and adults with SMA types 1-3. It boosts SMN2’s production of a functional SMN protein, potentially restoring its levels and function.
AVXS-101, an investigational gene therapy being studied to treat infants with SMA, has the potential to be the first one-time treatment for SMA. It is designed to deliver a functional copy of the SMN1 gene to patients’ motor nerve cells through a single administration directly into the blood.
AVXS-101 is being evaluated in clinical trials that include the Phase 3 SPR1NT trial (NCT03505099) in presymptomatic infants younger than 6 weeks (42 days) and diagnosed with SMA types 1-3; the Phase 3 STR1VE trial (NCT03306277) in SMA type 1 children younger than 6 months, and its European equivalent STR1VE-EU (NCT03461289); and the Phase 1 STRONG trial (NCT03381729) in type 2 children up to age 5 (60 months old).
Three of these trials are reported to still be recruiting patients; STR1VE is not. More information can be found by clicking on each trial’s NCT numbers, given above.
Considering AVXS-101’s promising clinical results, many analysts expect its FDA approval in the first quarter of 2019.