In 2022 and beyond, the care of patients with asthma will likely be transformed by novel monoclonal antibodies targeting cytokines, new asthma guidelines emphasizing precision medicine, and real-world evidence on the efficacy of newer asthma drugs. These were among the predictions made by Jon Romeo, DO, chair of the American College of Allergy, Asthma and Immunology Asthma Committee. In an interview with Pulmonology Advisor, Dr Romeo, an allergy and immunology specialist in Raleigh, North Carolina, offered his views on what’s ahead in 2022 as well as the most important developments in asthma care during the past year.
In 2021, research on monoclonal antibodies took center stage, said Dr. Romeo. Especially notable were several landmark studies on the monoclonal antibodies tezepelumab and astegolimab, both of which showed impressive efficacy in reducing asthma exacerbation rates.1,2 A few weeks before the end of 2021 ended, this research finally bore fruit when Tezspire, a tezepelumab-based pharmacologic agent (tezepelumab-ekko), received Food and Drug Administration approval.3-5
“I think those 2 drugs [tezepelumab and astegolimab] are fascinating and are going to be really helpful as being additional treatment options for patients with severe asthma,” said Dr Romeo. “We have a number of biologics already approved for severe, persistent asthma, all monoclonal antibodies directed at asthma, all of them directed at T2 asthma,” he noted. “But the drugs we currently have on the market really only treat certain subsets of people with severe asthma, either those with high eosinophil levels or those that have an allergic phenotype to their asthma.” This means that the asthma treatments that have been available thus far “don’t really work that well” for a significant subset of people with asthma, he explained.
“The most interesting thing about these 2 [new] drugs,” he continued, “is that they are focused on a different aspect, the cytokines, released from the respiratory epithelium, and they did show effectiveness in all comers with severe asthma regardless of their T2 status.”
Tezepelumab is a first-in-class human monoclonal antibody that works by blocking thymic stromal lymphopoietin, an epithelial cytokine involved in the initiation and persistence of airway inflammation.3-5 Astegolimab, a human immunoglobin G2 monoclonal antibody, selectively inhibits the interleukin-33 receptor, ST2, and in doing so may target pathogenic pathways in a wider spectrum of asthmatics.2
The FDA’s recent approval of Tezspire should change asthma care in the year ahead, he stressed. Tezspire, a monoclonal antibody used as an add-on maintenance treatment for patients 12 years of age and older with severe asthma, is administered subcutaneously to patients by a health care provider once every 4 weeks.3-5 “I think it’s going to be a real game-changer for those people who have not responded to the agents that we’ve had on the market the last couple of years.”
FDA approval of Tezspire followed the phase 3 NAVIGATOR trial (ClinicalTrials.gov Identifier: NCT03347279), the results of which were reported this spring in the New England Journal of Medicine.1 In that trial, investigators found that participants receiving tezepelumab had approximately 50 percent fewer asthma exacerbations relative to placebo. The trial included 1059 participants who were 12 to 80 years old (528 who received tezepelumab and 531 who received placebo) with severe uncontrolled asthma and a wide range of blood eosinophil counts. Participants received tezepelumab or placebo subcutaneously every 4 weeks for 52 weeks while they continued their previously prescribed inhaled glucocorticoids and additional controller medications. The trial found that individuals receiving tezepelumab showed improvement in asthma control as well as better asthma-related quality of life and lung function with tezepelumab.1
Findings of a phase 2b clinical trial of astegolimab (ClinicalTrials.gov Identifier: NCT02918019) were published in the Journal of Allergy and Clinical Immunology in April.2 The trial found that astegolimab reduced adjusted asthma exacerbation rates relative to placebo by 43%. In the multicenter randomized trial in 15 countries, 502 adults with poorly controlled severe asthma, 18 to 75 years old, were subcutaneously administered 1 of 3 doses of astegolimab or placebo every 4 weeks for a year. A broad population of patients saw improvement, including those who were eosinophil-low.2
Astegolimab has yet to complete phase 3 trials. “I’m guessing that’s not something that’s going to be available in the next 6 to 8 months, maybe not even the next 12 months, depending on what the studies show and then how long it takes to get approved through the FDA,” said Dr Romeo. “But I love that there is another drug in development directed at one of these cytokines.”
Both tezepelumab and astegolimab “fit into the broader shift towards our understanding of the bronchial epithelium,” noted Dr. Romeo. “We used to focus a bit more downstream, a little further along in the inflammatory cascade, at some of these later proteins that get developed that drive the inflammation in asthma. We are gaining a greater understanding of how important the respiratory epithelium is in creating the inflammation in asthma.”
Beyond these novel monoclonal antibodies, another major development in the management of asthma during the past year was the revision of the Global Initiative for Asthma guidelines,6 which came on the heels of the 2020 update of the National Asthma Education and Prevention Program guidelines.7 These updates had been long-awaited, said Dr Romeo.
One of the “more dramatic shifts we’ve seen in recommendations as far as managing asthma” in these guidelines is a push “to get away from using albuterol as a rescue medication and instead to consider using a low-dose inhaled steroid combined with formoterol,” said Dr Romeo. “Data has come out over the last few years that showed that by using these combo products of inhaled steroids with a long-acting beta-agonist, we were actually able to achieve a similar level of asthma control, or sometimes even superior asthma control, and it helps in preventing people from overusing their rescue inhalers as a kind of maintenance. Now you can actually use the same inhaler for both maintenance and rescue, adjusting the frequency and sometimes the dosing of the medication based on symptoms.”
Another consequential development in asthma care evident in the new asthma guidelines is an emphasis on developing a precision medicine approach to asthma control. Instead of “having blanket recommendations for all people with asthma,” clinicians are being encouraged to “more precisely treat the individual,” said Dr. Romeo.
“There’s a lot of research going on right now,” he added. “The consortium PrecISE [Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network] (ClinicalTrials.gov Identifier: NCT04129931) is enrolling a lot of patients and trying to learn about different biomarkers that identify people with certain subtypes of asthma to do more targeted therapy for the individual.8 There’s a big push in medicine in general, but certainly in asthma, to start to home in on biomarkers that tell us what’s driving asthma from a genetic or environmental standpoint and then, over time, that will allow us to devise treatments that will more individually treat patients.”
Dr. Romeo also foresees that some of the newer asthma drugs could be utilized in younger populations of patients. “For some [of these drugs], like omalizumab,9 which is Xolair, and benralizumab,10 which is Fasenra, they’ve done real-world studies, where they actually see how effective the medication is, retrospectively looking at people who were put on the drug and not in any kind of clinical trial setting,” he explained. The studies have confirmed “that these drugs do continue to work even if it’s not perfect conditions. I think there’s going to be a push to try to get younger populations [using] these drugs because they’re just so effective, and for young kids we don’t have a lot of additional options outside of inhalers and steroids right now.”
1. Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021; 384(19):1800-1809. doi: 10.1056/NEJMoa2034975
2. Kelsen SG, Agache IO, Soong W, et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial. J Allergy Clin Immunol. 2021;148(3):790-798. doi: 10.1016/j.jaci.2021.03.044
3. FDA approves Tezspire (tezepelumab-ekko) in the US for severe asthma. News release. Amgen. December 17, 2021. Accessed January 7, 2022. https://www.multivu.com/players/English/8812852-amgen-fda-approval-tezepelumab-severe-asthma-inflammation/
4. Tezspire. Package insert. Amgen; 2021. Accessed January 7, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761224s000lbl.pdf
5. Park, B. Tezspire approved as add-on maintenance treatment for severe asthma. MPR. Dec. 20, 2021.
6. Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J. 2021;59(1):2102730. doi:10.1183/13993003.02730-2021
7. Expert Panel Working Group of the National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC). 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217-1270. doi:10.1016/j.jaci.2020
8. Ivanova A, Israel E, LaVange LM, et al. The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations. J Biopharm Stat. 2020;30(6):1026-1037. doi: 10.1080/10543406.2020
9. Bousquet J, Humbert M, Gibson PG, et al. Real-world effectiveness of omalizumab in severe allergic asthma: a meta-analysis of observational studies. J Allergy Clin Immunol Pract. 2021;9(7):2702-2714. doi: 10.1016/j.jaip.2021.01.011
10. Kavanagh JE, Hearn AP, Dhariwal J, et al. Real-world effectiveness of benralizumab in severe eosinophilic asthma. Chest. 2021;159(2):496-506. doi: 10.1016/j.chest.2020.08.2083