— The evidence has significant limitations, and no firm estimate of net health benefit versus best supportive care was able to be determined for either nadofaragene firadenovec or oportuzumab monatoxs; the evidence is also inadequate to enable a clear comparison of these treatments to each other or to other active treatments —

— Based on the estimates derived from single-arm trials of patient benefits from delay of metastasis and need for cystectomy, ICER calculates an annual health benefit price benchmark range of approximately $118,000-$204,000 for both agents; the underlying limitations in the clinical evidence create substantial uncertainty in these price benchmarks —

— At an upcoming November 20 virtual meeting, the Midwest Comparative Effectiveness Public Advisory Committee will review the evidence, hear further testimony from stakeholders, and deliberate over these treatments’ comparative clinical effectiveness, other potential benefits, and long-term value for money —

BOSTON, November 6, 2020 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of nadofaragene firadenovec (Adstiladrin®, FKD Therapies Oy and FerGene) and oportuzumab monatox (Vicineum™, Sesen Bio) for the treatment of non-muscle invasive bladder cancer (NMIBC) that is unresponsive to Bacillus Calmette-Guerin (BCG) intravesical therapy.

“For many patients with BCG-unresponsive NMIBC, there are limited interventions available that preserve the bladder,” said David Rind, MD, ICER’s Chief Medical Officer. “While our review of the evidence suggests that both nadofaragene firadenovec and oportuzumab monatox may provide benefits for patients, more rigorous trials are needed. The lack of a placebo or active comparator in pivotal trials, though meeting FDA guidance, leaves clinicians, patients, and other stakeholders with significant uncertainty around comparative benefits and the magnitude of those benefits. Additionally, without longer-term data, it is impossible to know how often these therapies allow patients to progress past the point where removal of the bladder (cystectomy) is curative. If the FDA approves these therapies, we are hopeful that the manufacturers will not only price them in a responsible manner, but also continue to build the evidence base around their safety and efficacy.”

This Evidence Report will be reviewed at a virtual public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) on November 20, 2020. The Midwest CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

Significant limitations exist in the available clinical trial evidence, but available evidence suggests that both nadofaragene firadenovec and oportuzumab monatox are at least comparable to best supportive care and may provide a net health benefit ranging from small to moderate (“C++”). The current evidence is insufficient (“I”) to compare these interventions to each other or to commonly used active treatment options gemcitabine ± docetaxel and pembrolizumab.

Key Cost-Effectiveness Findings

Neither drug has received FDA approval yet, so there is no known US market price. Based on the available data from single-arm trials suggesting delay in metastasis and requirement for cystectomy compared to historical estimates of outcomes with best supportive care, ICER’s recommended health-benefit price benchmark (HBPB) ranges are $118,000-$198,000 per year for nadofaragene firadenovec and $119,000-$204,000 per year for oportuzumab monatox.

These HBPB ranges should be viewed as an upper bound on pricing, because ICER’s cost-effectiveness model is comparing these therapies to best supportive care. Most clinicians caring for patients with BCG-unresponsive NMIBC who choose not to have cystectomy would likely use treatments with at least some short-term efficacy.

The HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.