Current & Emerging Treatments

The numerous clinical trials for these compounds in T2I diseases is beyond the scope of this content. However, a few recent studies are worth highlighting:

• Dupilumab was FDA approved in September 2024 as an add-on maintenance treatment for adult patients with inadequately controlled COPD and an eosinophilic phenotype based on the BOREAS and NOTUS clinical trials. It is the first anti-T2I biologic to be approved for the condition.
  
  In the phase 3 BOREAS trial (N=939), COPD patients with blood eosinophil count of at least 300/mL and elevated exacerbation risk received dupilumab or placebo every 2 weeks.¹² The annualized rate of moderate or severe exacerbations was lower for dupilumab versus placebo (rate ratio: 0.70, 95% CI: 0.58-0.86; P < .001). Significant improvements with dupilumab were also noted for pre-bronchodilator FEV1 that was maintained through to week 52, as well as St. George’s Respiratory Questionnaire and ERS-COPD scores at week 52. Adverse events were similar between dupilumab and placebo. In the replicate phase 3 NOTUS trial, dupilumab was also associated with fewer exacerbations and better lung function compared to placebo.¹³
• Lebrikizumab was FDA approved in September 2024 for the treatment of adults and pediatric patients 12 years of age and older who weigh at least 40 kg with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The approval was based on the outcomes for the ADvocate 1, ADvocate 2, and ADhere studies. The former two demonstrated significant improvements in IGA scores 0-1 and EASI-75 response at 16 weeks for AD patients treated with lebrikizumab monotherapy although there were higher rates of conjunctivitis in the lebrikizumab group.¹⁴ These findings were consistent with the 16-week findings in the ADhere study that assessed lebrikizumab in combination with TCS.¹⁵
• Nemolizumab was FDA approved in September 2024 for the treatment of adults with PN based on the outcomes of the OLYMPIA 1 and OLYMPIA 2 trials. In OLYMPIA 2 (N=274), itch responses at week 16 were 56.3% versus 20.9% for nemolizumab versus placebo, respectively (37.4 percentage point difference, 95% CI: 26.3-48.5), while PP-NRS scores of less than 2 were 35.0% versus 7.7%.¹⁶ At Week 16 in the OLYMPIA 1 trial, patients receiving nemolizumab versus placebo similarly achieved a greater ≥4- point improvement in PP NRS (58.4% vs 16.7%; P< .0001).¹⁷

Investigational Therapies:

There are several therapies in under investigation for type 2-mediated diseases, including:

• Depemokimab. This long-acting IL-5 inhibitor is in late-stage clinical trials for asthma (SWIFT 1 and SWIFT 2), eosinophilic granulomatosis with polyangiitis (OCEAN), CRSwNP (ANCHOR), and hypereosinophilic syndrome (DESTINY).^18,19
• Dupilumab. This IL4/IL13 inhibitor is in late-stage clinical trials for BP (LIBERTY-BP ADEPT); and CSU (LIBERTY-CUPID Study C).²⁰
• Itepekimab. This IL-33 inhibitor is being studied for COPD (AERIFY-1 and AERIFY-2).²¹
• Stapokibart. This humanized IL-4Rα monoclonal antibody is in Phase 3 development for AD (NCT04893707), PN (NCT06424470), CRSwNP (CROWNS-2), moderate-to-severe asthma (NCT05761028), allergic rhinitis (MERAK), and COPD (NCT06547333).^22-24