High maintenance rates for novel IL-13 inhibitor in AD

Up to 80.6% of Phase 3 ADvocate trial responders, based on dosing interval, stayed clear or almost clear of lesions from weeks 16 to 52, according to the IGA scale.

The trials assess the efficacy and safety of lebrikizumab in atopic dermatitis

The phase 3 ADvocate 1 and 2 trials (NCT04146363, NCT04178967) investigated monotherapy with lebrikizumab versus placebo in patients with moderate-to-severe AD1. “We are going to talk about people who responded in the initial 16 weeks and then what happened to them over the course of 52 weeks,” Prof. Andrew Blauvelt (Oregon Medical Research Center, OR, USA) pointed out. Responders were adolescents (≥ 12 years) and adults (≥ 18 years), who reached an Eczema Area and Severity Index (EASI)75 or an IGA 0/1, which means almost clear or clear skin at week 16 of the trials.

At week 16, 43.1% and 33.2% of study drug participants achieved an IGA 0/1 and 58.8% and 52.1% an EASI75 improvement in both trials2. The Responders were then re-randomised to 3 different study arms: continue 250 mg of lebrikizumab every 2 weeks (Q2W), change to an every 4-week (Q4W) dosing, or placebo Q2W. At baseline, the average age ranged from 33 to 37.5 years, 45.2% to 65.6% participants were women, and the mean EASI varied between 2.0 and 2.9.

Emergent adverse events were mostly mild and moderate

The results of ADvocate 1 and 2 at week 52 showed 75.8% and 64.6% maintaining IGA 0/1 on the Q2W lebrikizumab regimen in comparison with 74.2% and 80.6% in the Q4W arms. Furthermore, a substantial rate of participants in the placebo arms continued to have IGA 0/1: 46.5% and 49.8%. “If we look now at EASI 75, we also see very similar results, the Q2 week dosing is very similar to the Q4 week dosing and we still have very high responses in the participants randomised to placebo,” Prof. Blauvelt elaborated.  The same was true for the maintenance of pruritus improvements.

As for safety results from weeks 0-52, treatment emergent adverse events were mostly mild (31.1% and 27.5%) and moderate (22.8% and 35.9%). “The highlight here is the percentage of conjunctivitis of 8.3% in one study, 8.1% in the other study; what we would expect with the mechanism of action, but at levels that I think are quite reasonable,” Prof. Blauvelt commented. Collectively, the conjunctivitis cluster was 13.5% and 14.7% through week 52, but according to Prof. Blauvelt, the actual rate went down from week 16 to 52.

“The study really showed that specific targeting of IL-13 with lebrikizumab either Q2 or Q4 has high maintenance of efficacy and is reasonably tolerated and safe in adolescents and adults with atopic dermatitis,” he concluded.

References
  1. Blauvelt A. Efficacy and safety of lebrikizumab in moderate-to-severe atopic Dermatitis: 52-week results of two randomized, double-blinded, placebo-controlled phase 3 trials (ADvocate1 and ADvocate2). D1T01.3D, EADV Congress 2022, Milan, Italy, 7–10. September.
  2. Silverberg JI, et al. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.