Positive Atopic Dermatitis Data On Lilly's Newly-Approved Olumiant
Just Received European Green Light For Skin Disorder
Executive Summary
It has gone under the radar that Eli Lilly and Incyte's Olumiant has recently become the first JAK inhibitor to be approved anywhere for atopic dermatitis and the companies have been touting promising long-term data on the therapy as it expands beyond rheumatoid arthritis.
Days after Olumiant became the first JAK inhibitor to be approved in Europe for atopic dermatitis,Eli Lilly and Company and partner Incyte Corporation have presented more positive data on the drug for the skin disease and highlighted its potential as a treatment for alopecia.
The US giant gave little fanfare to the European Commission's approval last week for Olumiant (baricitinib) for the treatment of adults with moderate to severe atopic dermatitis who are candidates for systemic therapy. The green light was a swift one given that the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) only issued a positive opinion at the end of September, noting that the drug, which has been on the market in the EU since 2017 for rheumatoid arthritis (RA), is the first medicine for the condition also known as eczema that patients can take orally.
The EU approval, the first global thumbs-up for Olumiant in this indication, was based on Lilly and Incyte's extensive Phase III BREEZE-AD program and the companies have presented new long term data at the virtual European Academy of Dermatology and Venereology congress (29-31 October) from the BREEZE-AD3 study.
The study assessed responders by the validated Investigator Global Assessment score of clear or almost clear skin (vIGA 0,1) and partial responders (vIGA 2) after 16 weeks of treatment. At the start of BREEZE-AD3, 45.7% of responders and partial responders on 4mg of baricitinib had a vIGA-AD score of 0 or 1, while 40% had a vIGA-AD score of 0 or 1 after 68 weeks of continuous therapy.
Similarly, at the start of BREEZE-AD3, 46.3% of responders and partial responders on 2mg had a vIGA-AD score of 0 or 1, while 50% had a vIGA-AD score of 0 or 1 after 68 weeks. Lotus Mallbris, head of immunology development at Lilly, said "We're encouraged by the long-term baricitinib efficacy and safety data being presented at EADV, which reinforce the potential role this medicine could play in helping people living with atopic dermatitis."
Challenging Dupixent?
The eczema market is a highly competitive one and Olumiant could soon be joined by rival JAK inhibitors, notably AbbVie Inc.'s Rinvoq (upadacitinib) and Pfizer Inc.'s abrocitinib. Analysts at Jefferies issued a note on 13 October based on a call with "one of the world's pre-eminent atopic dermatitis experts" who said that while the JAK inhibitors offer the added bonus of oral convenience, Sanofi and Regeneron Pharmaceuticals, Inc.'s subcutaneous interleukin-4 and IL-13 receptor antagonist Dupixent (dupilumab) is likely to remain treatment of choice thanks to its favourable risk/benefit profile. (Also see "AbbVie's Rinvoq Bolsters Its Potential In Atopic Dermatitis" - Scrip, 22 Jul, 2020.) (Also see "Pfizer’s Abrocitinib Quick Off The Mark In Atopic Dermatitis" - Scrip, 19 Mar, 2020.)
The expert argued that tolerability and safety signals are a concern for JAK inhibitors and could limit use for atopic dermatitis to certain populations, such as older adolescents to middle-age adults. The most common side effects with Olumiant seen in clinical trials include increased LDL ('bad') cholesterol, upper respiratory tract infections and headache, the EMA noted. (Also see "Sanofi Touts Positive Dupixent Data For Severe Childhood Asthma" - Scrip, 13 Oct, 2020.)
Effective For Alopecia Areata
It was a busy weekend for Lilly and Incyte as they also presented data at the Fall Clinical Dermatology meeting from the Phase II portion of BRAVE-AA1, an ongoing Phase II/III study evaluating Olumiant for patients with alopecia areata, the autoimmune disorder that can cause unpredictable hair loss on the scalp, face and other areas of the body.
At week 36, the proportion of patients achieving the primary endpoint of a Severity of Alopecia Tool (SALT) score ≤20, defined as having 20% or less of scalp hair loss and considered as clinically meaningful improvement, was significantly greater in baricitinib 2mg (33.3%, p=0.016), and 4mg (51.9%, p=0.001) groups compared to placebo (3.6%). The proportion of adults achieving no hair loss or limited hair loss on the patient-reported outcomes (PRO) were significantly greater in the 2mg and 4mg groups compared to placebo. Patients receiving the latter dose improved growth of eyebrows and eyelashes as assessed by the clinician-reported outcome and PRO measures.
Patients with AA "deal with unpredictable and long-lasting episodes of hair loss and many don't find relief from the therapies that are currently used," Mallbris said. She added, "We look forward to continuing the clinical development program for baricitinib in hopes of becoming the first US Food and Drug Administration-approved treatment option for adults with AA." In March, the FDA granted breakthrough therapy designation to Olumiant in this indication.
Lilly and Incyte see Olumiant as a pipeline in a pill but its blockbuster potential has been hampered because it was only approved for RA in the US (in 2018) at the 2mg dose and with a black box warning on its label for risk of infections, cancer and blood clots. However third quarter sales were impressive, rising 41% to $162m. (Also see "Trulicity Takes Hit From Payer Mix, But Lilly Emerges From Q3 Ahead" - Scrip, 27 Oct, 2020.)
Lilly is also continuing conversations with the FDA around the potential for emergency use authorization of Olumiant after it yielded a numerical decrease in deaths when given in combination with Gilead Sciences, Inc.’s Veklury (remdesivir) compared with Veklury alone in hospitalized COVID-19 patients. (Also see "Coronavirus Update: Lilly To Seek EUA For Olumiant" - Scrip, 9 Oct, 2020.)