Phase 3 Results for Baricitinib in Atopic Dermatitis Indicate Efficacy, Safety
FEBRUARY 04, 2019
Cecilia Pessoa Gingerich
Lotus Mallbris, MD, PhDTopline results from a pair of phase 3 studies of baricitinib monotherapy for adults with moderate to severe atopic dermatitis show that the studies met their primary efficacy endpoints.
Both clinical trials, BREEZE-AD1 and BREEZE-AD2, compared baricitinib to placebo in adult patients with moderate to severe atopic dermatitis. The primary endpoint was the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 with a ≥2 point improvement. At week 16 for each trial, compared to patients in the placebo arm, a statistically significant proportion of patients in the active treatment arm achieved a qualifying IGA score, meeting the primary endpoint.
Currently, just one treatment is approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis: dupilimab. However, the need for treatment options remains.
“Up to 3% of the population has atopic dermatitis and 25% of them have moderate to severe atopic dermatitis,” said Lotus Mallbris, MD, PhD, vice president of immunology development at Eli Lilly and Company, the sponsor for both trials, in an interview with MD Magazine®. “There is a huge unmet need and opportunity for innovation.”
Mallbris characterized the urgent need for research and new options for this condition as similar to the state of psoriasis a decade ago when she became involved in psoriasis research.
“Atopic dermatitis is the psoriasis of 10 years ago,” Mallbris told MD Mag, recalling how little attention was paid to psoriasis at that time. “We can do much better and our patients deserve to request more.”
BREEZE-AD1 and BREEZE-AD2 enrolled 600 and 750 participants, respectively. The studies both randomized participants to a high-, mid-, or low-dose baricitinib arm, or to placebo. The baricitinib doses tested were 4 mg, 2 mg, and 1 mg. All participants had been diagnosed with moderate to severe atopic dermatitis for at least 12 months and had had an inadequate response to or intolerance of existing topical treatments within 6 months before screening.
On the safety side of the studies, the company reported that treatment-emergent adverse events and serious adverse events were similar between baricitinib treatment and placebo. The most common treatment-emergent adverse events were nasopharyngitis and headache.
During the FDA approval process for baricitinib for the treatment of moderately-to-severely active rheumatoid arthritis, there was concern about the safety of the proposed 4 mg dose. The FDA initially rejected the company’s application for baricitinib due to safety concerns about dosage levels and an imbalance of thromboembolic events that occurred during placebo-controlled phase 2 and 3 trials. Subsequently, an FDA Advisory Committee recommended the approval of baricitinib at a lower dosage, voting 10-5 to support a smaller 2 mg dose of baricitinib for this indication.
There were no venous thromboembolic events, major adverse cardiovascular events (MACE), or deaths in either BREEZE-AD1 or BREEZE-AD2 Mallbris said. However, she noted that the results from these 2 clinical trials only represent data for 16 weeks of treatment.
BREEZE-AD1 and BREEZE-AD2 are just the first 2 of 5 studies in a planned placebo-controlled program for baricitinib in atopic dermatitis. The remaining studies will examine other patient populations, test baricitinib in combination with topical corticosteroids, and provide longer-term data.
Mallbris said that further details from BREEZE-AD1 and BREEZE-AD2 will be presented at an upcoming meeting and published. The company expects to announce topline results from the other studies of baricitinib for atopic dermatitis later this year.