ADvocate 1 and ADvocate 2 are 52-week randomized, double-blind phase 3 studies designed to evaluate lebrikizumab as monotherapy in adult and adolescent patients with moderate to severe AD.
Lebrikizumab was found to produce improvements in skin clearance and itch for patients with atopic dermatitis (AD) who achieved a clinical response at week 16 through 1 year of treatment, according to results from a pair of phase 3 monotherapy studies featured in an oral presentation at the 31st European Academy of Dermatology and Venerology Congress.
Lebrikizumab is a novel monoclonal antibody designed to bind interleukin (IL)-13 with high affinity, slow disassociation rate and high potency to specifically prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signaling, which inhibits the biological effects of IL-13 efficiently.
"Despite available treatment options, many patients with atopic dermatitis experience distressing symptoms every day over the course of years. Thus, there is a clear need for new therapies that maintain long-term results," said lead study author of ADvocate analyses Andrew Blauvelt, MD, board-certified dermatologist, president of Oregon Medical Research Center, in a press release. "Lebrikizumab helped patients reduce the impact of atopic dermatitis by maintaining long-lasting skin clearance and itch relief with dosing at every four weeks in the ADvocate studies. These data help deepen our understanding of the role lebrikizumab may play in treating atopic dermatitis and will assist practitioners to improve clinical outcomes for their patients with this chronic disease."
Efficacy was seen with every 4-week dose following a 16-week induction period with lebrikizumab every 2 weeks, which produced a similar impact to every 2 week dosing, according to the investigators. ADvocate 1 and ADvocate 2 are 52-week randomized, double-blind phase 3 studies designed to evaluate lebrikizumab as monotherapy in adult and adolescent patients with moderate to severe AD.
Patients received lebrikizumab 500 mg initially and at 2 weeks during the 16-week treatment period, followed by lebrikizumab 250 mg or placebo every 2 weeks. There was a maintenance period in which patients with moderate-to-severe AD who achieved a clinical response after 16 weeks of lebrikizumab treatment were re-randomized to receive lebrikizumab every 2 weeks or 4 weeks or placebo for an additional 36 weeks.
Patients who needed rescue treatment during the induction period or who did not meet protocol-defined response criteria at 16 weeks received lebrikizumab every 2 weeks for an additional 36 weeks.
The safety profile among patients at 52 weeks was consistent with the induction phase of the trials and previous lebrikizumab studies in AD. Further, the incidence rate of treatment-emergent adverse events (AEs) remained stable over time in patients with lebrikizumab. The proportion of lebrikizumab-treated patients who reported AEs in ADvocate 1 and ADvocate through week 52 was 58% and 68%, respectively.
Most AEs across the 2 studies were mild or moderate in severity, nonserious, and did not lead to treatment discontinuation, with the most commonly reported being conjunctivitis, common cold, and headache.
"Based on the robust and clinically meaningful results from our clinical trial program in atopic dermatitis, we believe lebrikizumab, if approved, could become a first-line treatment for dermatologists and many of their patients with moderate-to-severe disease who suffer from debilitating symptoms and seek new treatment options and prefer less frequent dosing," said Lotus Mallbris, MD, PhD, vice president of global immunology development and medical affairs at Eli Lilly, in a press release.
Lebrikizumab Dosed Every Four Weeks Maintained Durable Skin Clearance in Lilly's Phase 3 Monotherapy Atopic Dermatitis Trials. Lilly. September 8, 2022. Accessed September 12, 2022. https://investor.lilly.com/news-releases/news-release-details/lebrikizumab-dosed-every-four-weeks-maintained-durable-skin