Benzinga | Apr 23, 2021 10:06AM EDT

Eli Lilly Reports OLUMIANT Showed Improvements In Severity, Extent Of Atopic Dermatitis, Other Patient-Reported Outcomes In Phase 3 Analyses

Through new analyses of BREEZE-AD5 Phase 3 clinical trial data and an extended safety analysis across multiple trials, Eli Lilly and Company (NYSE:LLY) and Incyte's (NASDAQ:INCY) OLUMIANT(r) (baricitinib) 2-mg tablet taken once daily showed improvement in key measured treatment outcomes compared to placebo, and helped further characterize the long-term safety profile in adults with moderate to severe atopic dermatitis (AD). In one BREEZE-AD5 analysis, OLUMIANT provided concurrent improvements in the severity and extent of AD, other key symptoms and quality of life as early as one week, as measured by percent change from baseline compared to placebo. In a separate BREEZE-AD5 analysis, adults with AD on 10-50% of their bodies at baseline who were treated with OLUMIANT showed significant improvements in the severity and extent of disease compared to placebo. In the integrated safety analysis of eight AD studies of OLUMIANT, there were no increases in rates for treatment-emergent adverse events, serious adverse events or serious infections with long-term OLUMIANT therapy compared to the placebo-controlled period. These results are being presented virtually at the American Academy of Dermatology's Virtual Meeting Experience (AAD VMX), April 23-25, 2021.

"Atopic dermatitis is the most common chronic, inflammatory skin disease among adults and can pose significant challenges for those who suffer from this debilitating disease," said Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly. "We are encouraged by these additional new analyses of the BREEZE-AD5 study results, in which OLUMIANT showed early improvement across multiple symptoms among patients with moderate to severe atopic dermatitis. We are pleased the extended safety analysis helps further define the long-term safety profile of OLUMIANT in atopic dermatitis."

OLUMIANT 2-mg Concurrently Improved Extent, Severity and Key Symptoms of AD in as Early as One Week

In a post-hoc analysis of BREEZE-AD5, patients treated with OLUMIANT 2-mg showed statistically significant and concurrent improvements in the extent and severity of AD, as well as key symptoms such as itch, nighttime awakenings due to itch, skin discomfort and pain, and quality of life, as early as one week as measured by percent change from baseline compared to placebo. Patients taking OLUMIANT had statistically significant improvements from baseline (p<0.05) across all measures compared to placebo at one week and four weeks:

* Skin Measures: Eczema Area and Severity Index (EASI), which is a validated, clinical scoring system measuring the extent and severity of AD: At one week: 25.3% for OLUMIANT vs. 7.2% for placebo At four weeks: 50.9% for OLUMIANT vs. 24.0% for placebo

* Key Symptoms: Itch Numeric Rating Scale (NRS): At one week: 13.5% for OLUMIANT vs. -0.2% for placebo At four weeks: 29.0% for OLUMIANT vs. 12.5% for placebo Skin Pain NRS (Skin discomfort and pain): At one week: 12.0% for OLUMIANT vs. 2.6% for placebo At four weeks: 27.6% for OLUMIANT vs. 13.6% for placebo AD Sleep Scale (ADSS) Item 2 (number of nighttime awakenings due to itch): At one week: 20.9% for OLUMIANT vs. 3.9% for placebo At four weeks: 37.6% for OLUMIANT vs. 14.1% for placebo

* Composite Outcomes, Including Quality of Life: Dermatology Life Quality Index (DLQI): At one week: 27.2% for OLUMIANT vs. 12.9% for placebo At four weeks: 40.4% for OLUMIANT vs. 17.5% for placebo Patient Oriented Eczema Measure (POEM): At one week: 18.0% for OLUMIANT vs. 6.7% for placebo At four weeks: 29.3% for OLUMIANT vs. 10.8% for placebo

For methodology, see "About the Analyses" section below.

Patients with AD on 10-50% of Their Bodies at Baseline Treated with OLUMIANT 2-mg Experienced Significant Improvements in Severity and Extent of AD

A post-hoc analysis of BREEZE-AD5 was conducted to evaluate the efficacy of OLUMIANT 2-mg based on baseline Body Surface Area (BSA), which measures the extent to which a patient's skin is affected by AD. At two weeks, 2 out of 10 patients with a BSA 10-50% at baseline who were treated with OLUMIANT saw significant improvements in the severity and extent of their AD compared to placebo (20.2% vs. 5.9%, p?0.01), as measured by a 75% improvement in Eczema Area Severity Index (EASI 75).

At 16 weeks, nearly 4 out of 10 patients with a BSA 10-50% at baseline who were treated with OLUMIANT saw significant improvements in the severity and extent of their AD compared to placebo (37.5% vs. 9.9%, p?0.001) as measured by EASI 75.

At 16 weeks, approximately 3 out of 10 patients with a BSA 10-50% at baseline who were treated with OLUMIANT saw significant improvements in the severity and extent of the AD compared to placebo (31.7% vs. 6.9%, p?0.001) based on achievement of clear or almost clear skin, as measured by the validated Investigator Global Assessment for Atopic Dermatitis [vIGA-AD (0,1)].

OLUMIANT was also evaluated in patients with BSA >50% at baseline. Among these patients, results for OLUMIANT were numerically higher but not statistically significant compared to placebo. Safety for the baseline BSA 10-50% subgroup was consistent with the overall safety population across the OLUMIANT clinical program in AD.

For methodology, see "About the Analyses" section below.

"Patients with moderate to severe atopic dermatitis may have different treatment needs given the extent and severity of their disease," said Eric Simpson, M.D., M.C.R., Professor of Dermatology and Director of Clinical Research at Oregon Health & Science University in Portland and co-author of these analyses. "These results are exciting because they can help provide more clarity to dermatologists on how patients with atopic dermatitis on 10-50% of their bodies may respond to a systemic therapy, such as OLUMIANT."

Long-Term Analysis Supports Safety Profile of OLUMIANT 2-mg in AD

The safety profile for OLUMIANT 2-mg was evaluated in eight AD clinical studies (six double-blind, randomized, placebo-controlled studies and two long-term extension studies). In the 16-week placebo-controlled period, there was no observed increase in rates of serious adverse events or serious infections with OLUMIANT therapy compared to placebo, and rates remained similar in the long-term extensions. There were no reports of deep vein thrombosis and pulmonary embolism across these studies.

OLUMIANT showed no increase in anemia, neutropenia, lymphopenia or elevated liver enzymes compared to placebo as measured by mean change from baseline, and there was no additional increase in these lab changes with long-term therapy. There was no increase in risk of eczema herpeticum with OLUMIANT compared to placebo (0.2% vs. 0.4%), but an increase in cases of herpes simplex (2.0% vs. 0.9%) was observed.

For methodology, see "About the Analyses" section below.

"Given how challenging this multidimensional disease is to treat, patients with AD need additional options that can help them manage their disease when other therapies have not been effective," Dr. Mallbris continued. "OLUMIANT has the potential to be the first oral JAK inhibitor approved for adults with moderate to severe atopic dermatitis in the U.S. When approved, it would also have one of the largest sets of available safety data in its class for AD."

About The Analyses

* Rapid and Concurrent Improvements in the Signs and Symptoms of Atopic Dermatitis with Baricitinib in the Phase 3 Study, BREEZE-AD5 440 patients from the Phase 3 BREEZE-AD5 trial were randomized 1:1:1 to once-daily placebo or OLUMIANT 1-mg or 2-mg. Percent changes from baseline were assessed for the following measures in the first four weeks of the study: EASI, itch NRS, skin pain NRS, ADSS item 2, DLQI and POEM. P-values shown above were not adjusted for multiplicity.

* Efficacy of Baricitinib 2-mg Stratified by Baseline Body Surface Area in Adults with Moderate to Severe Atopic Dermatitis In a post-hoc analysis, 293 patients from the Phase 3 BREEZE-AD5 trial were divided into subgroups of baseline BSA 10-50% and >50%. Subgroups were evaluated for the proportion of patients achieving a ?75% reduction in EASI (EASI 75) and vIGA-AD(tm) (0,1). Safety was also assessed in the subgroup of patients with BSA 10-50% at baseline. P-values shown above were not adjusted for multiplicity.

* Extended Safety Analysis of Baricitinib 2-mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from 8 Randomized Clinical Trials OLUMIANT 2-mg was studied in six double-blind, randomized, placebo-controlled studies and two long-term extension studies. Incidence rates (IR)/100 patient-years at risk (PYR) were calculated. The analysis included 1,598 patients who received OLUMIANT 2-mg for 1,434.2 combined patient years of exposure (median 330 days).

OLUMIANT, an oral JAK inhibitor discovered by Incyte and licensed to Lilly, is currently under review by the U.S. Food and Drug Administration as an investigational medication for the treatment of adults with moderate to severe AD. Outside the U.S., it is the first JAK inhibitor approved for AD in more than 40 countries. It is also being investigated for the treatment of adults with alopecia areata, systemic lupus erythematosus, juvenile idiopathic arthritis, COVID-19 and for its approved indication for rheumatoid arthritis.