ICER: Hereditary Angioedema Therapies Less Cost-Effective than Earlier Estimates

ICER’s updated analysis uses observational, real-world data for three therapies — Takhzyro, Haegarda, and Cinryze.

Larger price discounts are needed to reach common thresholds for cost-effectiveness for therapies to treat patients with hereditary angioedema attacks, according to an updated analysis from the Institute for Clinical and Economic Review (ICER).

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

In the updated analysis using claims data, 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, ICER officials said.

“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 of ICER, said in a statement.

The 2018 report found that long-term prophylaxis with either of the C1 inhibitors or Takhzyro resulted in fewer acute attacks and improved quality of life, but 2018 pricing of all three treatments exceeded traditional cost-effectiveness thresholds.

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.

Hereditary angioedema is a rare disease characterized by episodes of the accumulation of fluids outside of the blood vessels, which 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.