Efficacy and safety of rademikibart (CBP-201), a next-generation mAb targeting IL-4Rα, in adults with moderate to severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001).

BACKGROUND: Rademikibart (CBP-201) is a next-generation IL-4 receptor alpha-targeting antibody. OBJECTIVE: We sought to evaluate rademikibart in adults with moderate to severe atopic dermatitis. METHODS: A total of 226 patients were randomized, double-blind, to subcutaneous rademikibart (300 mg every 2 weeks [Q2W], 150 mg Q2W, 300 mg every 4 weeks [Q4W]; plus 600-mg loading dose) or placebo. Randomization began in July 2020. The trial was completed in October 2021. RESULTS: The WW001 phase 2 trial achieved its primary end point: significant percent reduction from baseline in least-squares mean Eczema Area Severity Index (EASI) to week 16 with rademikibart 300 mg Q2W (-63.0%; P = .0007), 150 mg Q2W (-57.6%; P = .0067), 300 mg Q4W (-63.5%; P = .0004) versus placebo (-39.7%). EASI scores decreased significantly with 300 mg Q2W and Q4W at the earliest assessment (week 2), with no evidence of plateauing by week 16. Significant improvements were also observed in secondary end points, including pruritus. Across the primary and secondary end points, efficacy tended to be comparable with 300 mg Q2W and Q4W dosing. Rademikibart and placebo had similar, low incidence of treatment-emergent adverse events (TEAEs) (48% vs 54%), serious TEAEs (1.8% vs 3.6%), TEAEs leading to treatment discontinuation (1.2% vs 1.8%), conjunctivitis of unspecified cause (2.9% vs 0%), herpes (0.6% vs 1.8%), and injection-site reactions (1.8% vs 1.8%). Although no discontinuations were attributed to coronavirus disease 2019, pandemic-related restrictions likely had an impact on trial conduct. CONCLUSIONS: Rademikibart was efficacious and well tolerated at Q2W and Q4W intervals. Q4W dosing is a more convenient frequency than approved for current therapies.

A Mini Review of the Impact of Baseline Disease Severity on Clinical Outcomes: Should We Compare Atopic Dermatitis Clinical Trials?

Based on clinical trials of systemic treatments in adults with moderate-to-severe atopic dermatitis (AD) reported between 2014 and 2023, we used linear regression to investigate relationships between baseline Eczema Area and Severity Index (EASI) scores and (1) study start date, (2) EASI response, and (3) rescue medication rates. Analysis 1 was conducted with all patients from monotherapy and combination therapy trials; analyses 2 and 3 used monotherapy trial placebo arms. Across 32 trials with a baseline inclusion criterion of EASI ≥ 16, baseline mean EASI scores decreased with study start date. The lowest and highest baseline mean EASI scores were 25.1 and 33.6 (median 21.1 and 30.5), reported for the WW001 Phase 2 trial of rademikibart (formerly CBP-201; start date, July 2020) and the SOLO1 Phase 3 trial of dupilumab (start date, December 2014), respectively. In placebo arms, lower baseline EASI scores tended to be associated with greater percent reductions in EASI scores at Week 16 and less rescue medication usage. The WW001 trial placebo arm had the lowest baseline EASI score (mean 25.2; median 22.1), lowest rescue medication rate (14.3%), and a large reduction in least squares mean EASI scores (- 39.7%) at Week 16. In summary, baseline mean EASI scores have decreased across clinical trials conducted during the last decade. Less severe AD at baseline tended to be associated with greater placebo response and less use of rescue medications in placebo arms. Intertrial differences in variables, such as baseline AD severity, limit the validity of indirectly comparing clinical trials.

Fixed combination of bimatoprost and timolol in patients with primary open-angle glaucoma or ocular hypertension with inadequate IOP adjustment.

OBJECTIVE: To assess the efficacy and tolerability of a fixed combination of bimatoprost and timolol (BTFC) in a large patient sample in a clinical setting. METHODS: In this multicenter, observational, noncontrolled, open-label study, patients (n = 1862) with primary open-angle glaucoma or ocular hypertension were treated with BTFC. Assessments were made at baseline, six weeks, and three months. RESULTS: Prior to starting BTFC, 92.3% of patients were taking other ocular hypotensive medications. In the overall group at three months, mean intraocular pressure was reduced from baseline (21.7 ± 4.5 mmHg and 21.8 ± 4.9 mmHg for the right and left eye, respectively) to 16.1 ± 3.0 mmHg for each eye (P < 0.0001). The majority of patients (92%) reported no adverse events. The most commonly reported adverse events (in >1% of patients) were eye irritation, and ocular and conjunctival hyperemia. Adherence to treatment was generally better than (35.4%) or the same as (57.5%) with prior therapy. BTFC tolerability was rated as excellent or good by 92.3% of physicians and 85.8% of patients. CONCLUSIONS: In a large group of patients with primary open-angle glaucoma or ocular hypertension, treatment with BTFC was associated with consistent reductions in IOP, improved adherence to treatment, and good tolerability.