Institute for Clinical and Economic Review Finds Treatments Prevent Hereditary Angioedema Attacks, but Cost-Effectiveness Uncertain and Sensitive to Frequency of Attacks

— As with all treatments for ultra-rare conditions, judgments of overall value require consideration of the broader patient benefits and contextual issues that will be discussed at the October 25 public meeting —

BOSTON, October 11, 2018 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of therapies for long-term prophylaxis against hereditary angioedema (HAE) attacks. HAE is an ultra-rare condition characterized by attacks of deep tissue swelling within the skin and/or mucosa. ICER’s report reviews three therapies for the prevention of HAE attacks: lanadelumab (Takhzyro™, Shire Plc), and two C1 inhibitors (Haegarda®, CSL Behring GmbH; and Cinryze®, Shire Plc). ICER’s earlier draft report also included an additional C1 inhibitor, Ruconest® (Pharming Healthcare, Inc.), which has since been removed from the assessment because the treatment is no longer under consideration for FDA approval for long-term prophylaxis.

“While long-term prophylaxis with all three therapies resulted in fewer acute attacks and improved quality of life for people living with hereditary angioedema, these improvements come at a substantial financial cost,” said David Rind, MD, Chief Medical Officer at ICER. “At their current prices, these treatments do not meet traditional cost-effectiveness thresholds. However, decision makers will need to be aware that even minor adjustments in our key assumptions could result in substantially different cost-effectiveness results, particularly for the two therapies that are administered subcutaneously, lanadelumab and Haegarda. During our public meeting, we will discuss these therapies and the limitations inherent to this particular analysis.”

This Evidence Report will be the subject of an upcoming public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s three independent evidence appraisal committees, on October 25, 2018. 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 Findings

All three drugs reviewed reduced the number and severity of HAE attacks compared with no long-term prophylaxis, and available data suggest few harms. Haegarda and lanadelumab have the additional benefit of being subcutaneously administered, which may decrease the burden and complexity of administration and avoid complications due to repeated intravenous infusions. Evidence provides high certainty that Haegarda and Cinryze provide a substantial net benefit compared with no prophylaxis. Evidence on lanadelumab was considered promising but inconclusive because of concerns about long-term safety with a new therapy that was only studied in short-term trials and small numbers of patients. Evidence was insufficient to compare the net health benefits among the three treatments.

Economic analyses assessing long-term cost-effectiveness found that all three treatments far exceed commonly cited thresholds of $50,000-$150,000 per quality-adjusted life year (QALY) gained, with $243,000 per QALY for Haegarda, $5,870,000 per QALY for Cinryze, and $1,020,000 per QALY for lanadelumab. To align costs with the added benefits for patients, discounts off the list price would need to be approximately 59% for Cinryze, 27% for Haegarda, and 33% for lanadelumab.

However, because the overall cost-effectiveness of prophylactic treatment balances the high treatment cost of prophylaxis with the avoided high costs associated with on-demand treatment of acute attacks, the economic modeling results are highly sensitive to assumptions made about variables such as the baseline rate of acute attacks and the likelihood that patients will switch dosing schedules over time for prophylactic therapy.

ICER’s report notes that decision-makers often give special considerations to therapies for ultra-rare diseases such as HAE that may lead to coverage and funding decisions at higher thresholds for cost-effectiveness.

Register here to attend the CTAF meeting in person or to watch by live webcast.

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.