Late Breaking: Zumilokibart Meets Primary End Point in Phase 2 Atopic Dermatitis Trial

All 3 dose regimens of zumilokibart (APG777), an investigational half-life-extended anti–interleukin 13 (IL-13) monoclonal antibody, met the primary end point in the phase 2 APEX Part B study of adults with moderate to severe atopic dermatitis (AD).¹ Melinda Gooderham, MSc, MD, FRCPC, presented the results as a late-breaking abstract at the 2026 European Academy of Dermatology and Venereology (EADV) Congress in Vienna.¹ AbbVie, which acquired Apogee Therapeutics and zumilokibart earlier this year, selected the mid-dose regimen for phase 3 development.²

Zumilokibart shares an epitope with lebrikizumab and carries a YTE amino acid modification in the Fc region, which increases neonatal Fc receptor–mediated recycling and extends half-life to 75–77 days.¹ APEX Part A, presented at EADV 2025, showed maintained responses through 52 weeks with every-12-week and every-24-week maintenance dosing.¹

APEX Part B (NCT07003425) is a randomized, double-blind, placebo-controlled phase 2 dose-regimen-finding study in adults with an Eczema Area and Severity Index (EASI) score of 16 or higher, a validated Investigator Global Assessment (vIGA) score of 3 or higher, and body surface area involvement of 10% or higher.¹˒³ Of 449 patients screened, 347 were randomized 1:1:1:1 and 346 received treatment with low-dose (n = 86), mid-dose (n = 85), or high-dose (n = 87) zumilokibart or placebo (n = 88). The study was supported by Apogee Therapeutics.¹

The mid-dose induction regimen matched APEX Part A, at 720 mg at weeks 0 and 2, then 360 mg at weeks 4 and 12. Modeled exposure relative to lebrikizumab ranged from approximately 40% to 50% lower with the low dose to 90% to 100% greater with the high dose.¹

The primary end point was EASI 75 at week 16. Response rates were 65.9% with the mid dose, 61.6% with the high dose, 50.5% with the low dose, and 23.4% with placebo (P < .001 for each vs placebo, using multiple imputation with nonresponder imputation).¹

"We saw two thirds of patients on the mid dose achieving an EASI 75 at week 16, and this is comparable to what we saw in Part A,” Gooderham, dermatologist, medical director at the SKiN Centre for Dermatology, and principal investigator for the SKiN Research Centre in Peterborough, Ontario, Canada, said.

Zumilokibart Secondary End Points and Safety Profile

Response rates at week 16 favored zumilokibart across key secondary end points. Rates of vIGA-AD 0 or 1 were 46.0% with the mid dose, 33.4% with the high dose, 27.6% with the low dose, and 10.9% with placebo (P < .01 for all doses). EASI 90 rates were 47.4%, 35.8%, 28.2%, and 9.3%, respectively (P < .01 for all doses).¹

Among patients with a baseline itch score of 4 or higher, response rates for a 4-point or greater improvement on the Itch Numeric Rating Scale (I-NRS4) were 50.5% with the mid dose, 43.4% with the high dose, 35.7% with the low dose, and 13.9% with placebo. The mid dose showed significant skin improvement by week 1 and itch improvement by week 2.¹

Complete skin clearance (EASI 100) occurred in 16.5% with the mid dose and 12.6% with the high dose vs 3.4% with placebo (P < .01 and P < .05, respectively). Very low disease activity (EASI-90 plus I-NRS of 0 or 1, as observed) was reached by 20.6% with the mid dose vs 4.5% with placebo (P < .01).¹

Gooderham said, "That's one in six patients with clear skin by week 16," adding "one in five patients on the mid dose achieved both clear, almost clear skin and no to minimal itch."

Through week 16, adverse events (AEs) occurred in 60.0% (51/85) with the mid dose, 67.8% (59/87) with the high dose, 75.6% (65/86) with the low dose, and 67.0% (59/88) with placebo. Serious AEs and AEs leading to discontinuation each occurred in 1.2%–3.4% of patients, with no pattern across arms. The most common AEs (≥5% in any group) were nasopharyngitis, headache, noninfective conjunctivitis, upper respiratory tract infection, AD, and urinary tract infection.¹

Noninfective conjunctivitis occurred in 5.9% (5/85) with the mid dose and 11.5% (10/87) with the high dose vs 0% with placebo. Pooled conjunctivitis rates were 10.6% with the mid dose, 15.1% with the low dose, and 20.7% with the high dose. All cases were grade 1 or 2, and discontinuation due to conjunctivitis was less than 1%.¹

"Safety and tolerability was what we expected for inhibiting interleukin 13 with no new surprises,” Gooderham said.

She added in the AbbVie announcement, "Atopic dermatitis is a chronic disease, and the frequency of administration can be an important consideration when selecting a long-term therapy."²

The mid dose was selected for phase 3 based on early onset of efficacy, depth of response, and a safety profile consistent with IL-13 and IL-4/IL-13 therapies, according to the presentation.¹ The ADventure phase 3 program is scheduled to begin in the second half of 2026, with week 52 maintenance data on every-12-week and every-24-week dosing anticipated in the first half of 2027.¹

References

1. Silverberg J, Gooderham M, Eyerich K, et al. Efficacy and safety of zumilokibart (APG777), a half-life-extended anti-IL-13 antibody, in moderate-to-severe atopic dermatitis: primary results from the phase 2 APEX Part B dose-regimen-finding study. Presented at: 2026 Annual European Academy of Dermatology and Venereology Congress; September 30, 2026; Vienna, Austria.
2. AbbVie highlights positive results from the phase 2 APEX Part B study of zumilokibart in moderate to severe atopic dermatitis, as a late breaker at EADV 2026. AbbVie. September 30, 2026. Accessed September 30, 2026. https://www.prnewswire.com/news-releases/abbvie-highlights-positive-results-from-the-phase-2-apex-part-b-study-of-zumilokibart-in-moderate-to-severe-atopic-dermatitis-as-a-late-breaker-at-eadv-2026-302893602.html?tc=eml_cleartime
3. A long-term extension study to evaluate the safety and efficacy of APG777 in patients with atopic dermatitis previously treated with APG777. ClinicalTrials.gov identifier: NCT07003425. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT07003425