Report: Tezepelumab reduces severe asthma exacerbations, but unlikely to be cost-effective
Tezepelumab reduces exacerbations among patients who have severe asthma, including some types of asthma that lack other effective biologic therapies, according to a draft evidence report by the Institute for Clinical and Economic Review.
However, the report also found that tezepelumab (Tezspire; AstraZeneca, Amgen) yielded relatively small improvements in daily symptoms and quality of life, and models suggested it would exceed typical cost-effectiveness thresholds.
A monoclonal antibody, tezepelumab targets thymic stromal lymphopoietin via subcutaneous injection every 4 weeks. The Institute for Clinical and Economic Review (ICER) expects the FDA to make a regulatory decision on its use by the end of the year.
Clinical efficacy for severe asthma
ICER’s draft evidence report reviewed tezepelumab’s clinical effectiveness in treating severe asthma, comparing its use with omalizumab (Xolair; Genentech, Novartis) for patients with allergic asthma and with dupilumab (Dupixent; Sanofi Genzyme, Regeneron) for patients with eosinophilic asthma. The report also compared the efficacy of tezepelumab and dupilumab among patients who depend on chronic oral corticosteroids (OCS).
Tezepelumab substantially reduced the annualized asthma exacerbation rate (AAER) compared with placebo among a broad population of patients with severe asthma in two randomized trials, PATHWAY (RR = 0.29; 95% CI, 0.16-0.51) and NAVIGATOR (RR = 0.44; 95% CI, 0.37-0.53).
The monoclonal antibody also improved symptom scores in these trials, although these improvements (0.2 to 0.34) were smaller than the minimal clinically important differences of 0.5 on these scales.
“When you speak with patient groups and patients, they will tell you that [AAER is] not viewed as the most important outcome,” Steven D. Pearson, MD, MSc, founder and president of ICER, said during a webinar presenting the draft evidence report, adding that patients instead view improvement in daily symptoms as most important.
Compared with the standard of care, ICER gave tezepelumab a C++ rating for its use among all patients with severe asthma.
“In ICER language, that means we have moderate certainty that it is comparable or better, and better could be all the way up to substantially better,” Pearson said. “This is a difficult rating, given that there is still some potential concern about the new mechanism of action and relative short-term use among relatively few patients.”
Yet ICER said that tezepelumab may yield a proportionately greater benefit among Black patients, who have a greater prevalence of severe asthma.
In fact, asthma “is more than twice as common among Black children as among white children, and it does remain somewhat more common among Black adults,” Pearson said.
ICER cautions, however, that studies have not adequately enrolled Black Americans to demonstrate such a consistent effect.
Among patients with eosinophilic asthma, tezepelumab conferred similar improvements in symptom scores and AAER reductions as dupilumab.
Patients with non-eosinophilic asthma treated with tezepelumab experienced similar improvements in symptom scores as patients with eosinophilic asthma in the PATHWAY study, with only minimal improvement seen in NAVIGATOR.
Also, patients with non-eosinophilic asthma in PATHWAY had numerically greater AAER reductions with tezepelumab vs. placebo than patients with eosinophilic asthma (RR = 0.17 vs. RR = 0.34), whereas in NAVIGATOR, the reverse was true (non-eosinophilic, RR = 0.61 vs. eosinophilic, RR = 0.39).
Among patients with allergic asthma, the report found similar improvements in symptoms as those seen in older trials of omalizumab, whereas reductions in AAER were somewhat greater than with omalizumab.
Based on these data, the ICER report deemed there was insufficient evidence to make a distinction of efficacy in its evaluations of tezepelumab compared with dupilumab for eosinophilic asthma and compared with omalizumab for allergic asthma.
In the evaluation of patients with steroid-dependent asthma, data from the SOURCE trial showed patients treated with tezepelumab were not more likely to reduce their OCS dose at week 48 than patients treated with placebo (OR = 1.28; 95% CI, 0.69-2.35). Dupilumab, however, yielded a greater OCS dose reduction compared with placebo (70% vs. 42%; P < .001) in the VENTURE trial, and a greater proportion of patients had OCS dose reductions of 50% or more (80% vs. 50%; P < .001).
“So many patients and clinicians are interested in trying to reduce the use of systemic steroids for patients with severe asthma,” said Pearson.
Overall, the ICER report deemed tezepelumab at best is comparable with and may be somewhat less effective than dupilumab in treating steroid-dependent asthma, giving it a C- rating.
Finally, ICER noted that tezepelumab’s pricing is not yet known but anticipated prices indicate that it will not reach thresholds that traditionally are considered cost-effective in the U.S. market.
Economic models showed tezepelumab conferred gains of 1.09 quality-adjust life-years and 1.12 equal-value life-years.
Using a placeholder net price of approximately $28,000 per year based on the price of dupilumab, the ICER report estimated a cost of $430,000 per quality-adjust life-year gained and $422,000 per equal-value life-year gained, which exceed typical cost-effective thresholds.
Because its review is a draft evidence report, ICER invites all stakeholders to submit formal comments by email by 5 p.m. on Oct. 14. The organization said it will then review all comments and incorporate any necessary changes in its final evidence report.
Tezepelumab for severe asthma. https://icer.org/wp-content/uploads/2021/05/ICER_Severe-Asthma_Draft-Evidence-Report_091621.pdf. Published Sept. 16, 2021. Accessed Oct. 6, 2021.