Patients initiating therapy in real-world dataset had less frequent baseline attack rates than rates from clinical trials used in 2018 assessment; as a result, all three therapies are far less cost-effective than earlier estimates and would require a price discount of at least 50% to reach common thresholds of cost-effectiveness

ICER advances the role of credible real-world evidence in health technology assessment through fit-for-purpose data and analytics, enabled by the Aetion Evidence Platform®

BOSTON and NEW YORK, August 24, 2021 – The Institute for Clinical and Economic Review (ICER) today published an Observational Real-World Evidence (RWE) Update to its 2018 cost-effectiveness model of three therapies for long-term prophylaxis against hereditary angioedema (HAE) attacks: lanadelumab (Takhzyro®, Takeda), and two C1 inhibitors (Haegarda®, CSL Behring; and Cinryze®, Takeda).

“As ICER noted throughout our earlier assessment of these HAE therapies, our original economic models were highly sensitive to small changes in assumptions about the frequency of baseline attacks, the amount of on-demand treatment required, and the exact dosing regimens of prophylactic therapy,” said Jon Campbell, PhD, ICER’s Senior Vice President of Health Economics. “This atypically sensitive cost-effectiveness model, coupled with the high frequency and cost of HAE attacks, made this disease an ideal candidate for further RWE exploration. Collaborating with Aetion and the University of Washington, we are now able to use observational RWE to more accurately determine the therapies’ cost-effectiveness. De-identified claims data suggest that patients initiating prophylaxis therapy in the real world had fewer baseline attacks than that of individuals who participated in the clinical trials. As a result, all three assessed therapies require even larger price discounts to reach common thresholds for cost-effectiveness than what our models had originally projected in 2018.” 

Carolyn Magill, CEO of Aetion, stated: “For this RWE study, our researchers supplemented clinical trial findings by analyzing real-world data on the Aetion Evidence Platform to further clarify baseline attack rates, cost, and utilization. This initiative demonstrates the value of transparent and reproducible RWE to inform important decisions that impact patient care.”

Updated Cost-Effectiveness Findings

ICER’s updated health-benefit price benchmark (HBPB) range for Takhzyro is $218,900-$219,800 per year, which would require an approximate 53% discount off the treatment’s current US list price. (Using only the data and assumptions from the randomized clinical trials, our 2018 HBPB for Takhzyro had been between $537,200-$540,100.)

ICER’s updated HBPB for Haegarda is $247,700-$248,800 per year, which would require a 54% discount off the treatment’s current US list price. (Using only the data and assumptions from the randomized clinical trials, our 2018 HBPB for Haegarda had been between $522,200-$525,100.)

ICER’s updated HBPB for Cinryze is $139,800-$140,600 per year, which would require a 75% discount off the treatment’s current US list price. (Using only the data and assumptions from the randomized clinical trials, our 2018 HBPB for Cinryze had been between $307,500-$309,300.)

ICER’s 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.


ICER’s updated assessment leveraged observational RWE analyzed by Aetion, as part of the ongoing collaboration between the two organizations, and consistent with ICER’s commitment to expand use of RWE to complement other sources of information used in its value assessments. Aetion researchers used Optum’s de-identified Clinformatics® Data Mart, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans, to generate the RWE.

As broad stakeholder input was included within the initial assessment of these therapies, ICER proceeded with a condensed timeline for incorporating RWE to update its initial model for this re-assessment. Relevant input for the RWE pilot came from clinical experts and the manufacturers of the HAE therapies to inform the Research Protocol as well as how RWE was incorporated into the Modeling Analysis Plan.

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.

About Aetion

Aetion is a health care analytics company that delivers real-world evidence for the manufacturers, purchasers, and regulators of medical treatments and technologies. The Aetion Evidence Platform® analyzes data from the real world to produce transparent, rapid, and scientifically validated answers on safety, effectiveness, and value. Founded by Harvard Medical School faculty members with decades of experience in epidemiology and health outcomes research, Aetion informs health care’s most critical decisions — what works best, for whom, and when — to guide product development, commercialization, and payment innovation.

Aetion is based in New York City and backed by investors including New Enterprise Associates (NEA), Warburg Pincus, Flare Capital Partners, Greenspring Associates, Lakestar, B Capital, Foresite Capital, Town Hall Ventures, McKesson Ventures, Sanofi Ventures, EDBI, Johnson & Johnson Innovation—JJDC, Inc., UCB, Amgen Ventures, and Horizon Health Services, Inc. Learn more at and follow us at @aetioninc.