Therapies Reduce HAE Attacks, but Cost Too Much, Review Board Says

Long-term prevention with human formulations of the C1 esterase inhibitor — Cinryze or Haegarda — safely and effectively reduces the number of acute attacks in people with hereditary angioedema (HAE), but the therapies’ prices are too high, according to a report of the Institute for Clinical and Economic Review (ICER).

ICER compared the long-term clinical benefits and cost-effectiveness of three approved prophylaxis (preventative) therapies: two C1 inhibitors — Shire’s Cinryze and CSL Behring’s Haegarda — and a human monoclonal antibody — Shire’s Takhzyro (lanadelumab).

The nonprofit research institute has released its final report, as well as the report-at-a-glance. The report was reviewed at a public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, in October 2018.

ICER analysis showed that long-term prophylaxis with each of the therapies reduced the frequency and severity of HAE attacks and improved patients’ quality of life. However, an adequate comparison between the benefits and detriments of these therapies was unattainable in the absence of clinical trials comparing them and differences in trials’ design and populations.

While there was evidence supporting Cinryze and Haegarda superiority compared with on-demand therapy alone, Takhzyro’s lack of long-term safety data raised concerns about its potential risks and prevented adequate determination of its superiority.

Despite these concerns, CTAF members pointed out that all three therapies have the potential to significantly improve both patients’ and caregivers’ ability to return to work or school, and that Haegarda and Takhzyro offer a simpler administration — injection under the skin — than Cinryze — administration directly into the blood.

The ICER report also highlighted the need for longer-term studies of all three therapies, and assessment of their effect on patients’ quality of life using the disease-specific quality of life questionnaire (HAE-QoL), as well as on depression, anxiety, and school or work.

The report showed that all three therapies exceeded commonly cited thresholds for cost-effectiveness: from $50,000 to $150,000 per quality-adjusted life year (QALY) gained. QALY is a measure of disease burden, including the quality and quantity of life.

Haegarda required the smallest price reduction (28%) to be within traditional thresholds, followed by Takhzyro (34%) and Cinryze (60%).

The CTAF committee voted that Cinryze and Takhzyro represent a low long-term value for money when compared to on-demand therapy, and Haegarda’s value for money drew an evenly split vote between low and intermediate value.

According to ICER, decision-makers often give special considerations to therapies for ultra-rare diseases, including HAE, meaning it is possible that any of these treatments still might be covered or funded, even if they are exceeding the traditional cost-effectiveness threshold.

Decision-makers need to be aware that the economic models generated in this report “were very sensitive to small changes in assumptions about the frequency of attacks, the amount of on-demand treatment required, and the exact dosing regimens of prophylactic therapy,” and “relatively small changes in the price of prophylactic therapy greatly improved its cost-effectiveness,” David Rind, MD, ICER’s chief medical officer, said in a press release.

“Insurers and manufacturers should work together to achieve appropriate access to these important therapies at a price that patients and society can afford,” Rind said.

The CTAF committee also participated in a policy discussion that included physicians, patient advocates, manufacturer representatives, and payer representatives.

The resulting policy recommendations included: investment in Haegarda and Takhzyro to negotiate better prices; incorporation of head-to-head comparison of the treatments’ effects and standardized quality-of-life measures in clinical trials; and a combined effort between HAE specialists and patients to develop a consensus statement on when to start long-term prophylaxis in HAE patients, to guide policymakers and payers.