ICER Updates Assessment of Hereditary Angioedema Therapies

An analysis using claims data for three therapies to treat patients with hereditary angioedema attacks has found that larger price discounts are needed to reach common thresholds for cost-effectiveness, according to an updated analysis from the Institute for Clinical and Economic Review (ICER), the independent cost-effectiveness organization in Boston.

Hereditary angioedema is a rare disease characterized by episodes of the accumulation of fluids outside of the blood vessels that causes rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway, according to the National Organization for Rare Disorders. Symptoms typically begin in early childhood, and an estimated one in 50,000 to 150,000 people is affected worldwide.

Several therapies are approved to prevent the attack and swelling associated with the condition. In 2018, ICER’s cost-effectiveness model evaluated three of these therapies: Takeda’s Takhzyro (lanadelumab-flyo) and two C1 esterase inhibitors, CSL Behring’s Haegarda and Takeda’s Cinryze.

In the updated analysis, patients initiating therapy in the real-world had less frequent baseline attack rates than rates from clinical trials used in 2018 assessment. As a result, all three therapies would require a price discount of at least 50% to reach common thresholds of cost-effectiveness, according to ICER's calculations.

Jon Campbell, Ph.D.

“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,” Jon Campbell, Ph.D., ICER’s senior vice president of health economics, said in a statement.

One of the uncertainties in the 2018 model was the frequency and severity of attacks among patients who would be prescribed these therapies. ICER collaborated with Aetion and the University of Washington to use observational real-world evidence to assess the severity of attacks and update cost-effectiveness. This was a pilot project to explore how ICER can use real-world evidence with an emphasis on therapies that have been approved through accelerated approval pathways and are in use for over two years.

In this updated study, de-identified claims data suggest that patients using these three therapies to prevent angioedema had fewer baseline attacks than patients who participated in the clinical trials. The earlier, higher estimates of the number of angioedema attacks raised the price range under which the therapies would be considered cost-effective.

The updated assessment shows the need for even larger price discounts to reach common thresholds for cost-effectiveness. ICER uses a benchmark it developed, the health-benefit price benchmark (HBPB), a price range suggesting the highest U.S. price a manufacturer should charge for a treatment based on the amount of improvement in overall health patients receive from that treatment.

The updated benchmark range for Takhzyro is now $218,900 to $219,800 per year, which would require about 53% discount off the treatment’s current U.S. list price. Previously, using only the data and assumptions from the randomized clinical trials, ICER’s 2018 health-benefit price benchmark for Takhzyro had been between $537,200 to $540,100.

For Haegarda, the range is now $247,700 to $248,800 per year, which would require a 54% discount off the treatment’s current U.S. list price. In 2018, ICER had a benchmark range of between $522,200 to $525,100.

For Cinryze, the updated benchmark range is $139,800 to $140,600 per year, which would require a 75% discount off the treatment’s current US list price. In 2018, HBPB for Cinryze had been between $307,500 to $309,300.