- Eli Lilly and partner Incyte on Wednesday reported their inflammatory disease drug baricitinib, sold as Olumiant for arthritis and atopic dermatitis, helped people with severe cases of alopecia areata regrow hair in the first of two Phase 3 trials.
- Without providing specific details, Lilly and Incyte said both a low- and high-dose produced a statistically significant increase in hair regrowth versus placebo. Side effects were "consistent" with the known safety profile of baricitinib, which, though cleared for use in two diseases, has warnings about infections, malignancy and blood clots.
- There are no approved treatments for alopecia areata, an autoimmune disease that affects as many as 147 million people worldwide. That could soon change, as Lilly's drug and several others like it — medicines known as JAK inhibitors — are moving through late-stage trials. But several carry safety warnings, which could complicate their use in alopecia areata.
JAK inhibitors, which interfere with molecular pathways involved in inflammation, have become useful treatments for several autoimmune disease. As oral drugs, they're a convenient alternative to injectable biologics like Humira, and have demonstrated potential in multiple inflammatory conditions. The field's top-selling drug, Xeljanz, generated $2.4 billion in sales in 2020.
Alopecia areata has been viewed as a promising area of research for JAK inhibitors after a 2014 Nature paper showed they may help reverse hair loss. The disease, which occurs when the immune system attacks hair follicles, is the second-leading cause of baldness, which can lead to anxiety, depression and other health issues. There are no drugs specifically approved for the disease, though immunosuppressive drugs are used off-label. People can also opt for wigs and hairpieces or hair-regrowth methods like platelet-rich-plasma therapy or minoxidil.
JAK blockers, by contrast, are meant to tamp down the immune response and help regrow hair. That's led to significant interest among pharma companies and biotechs. Lilly and Incyte, Pfizer and Concert Pharmaceuticals each have programs in late-stage testing.
Select JAK inhibitors in Phase 3 testing for alopecia areata
|Company||Drug||Trial(s)||Primary completion date|
|Eli Lilly/Incyte||baricitinib||BRAVE-AA1, BRAVE-AA2||February 2021, for BRAVE-AA1|
|Pfizer||PF-06651600||ALLEGRO-2b/3, ALLEGRO-LT||December 2020* and August 2023|
|Concert Pharmaceuticals||CTP-543||THRIVE-AA1||February 2022|
*Results not yet disclosed SOURCE: Companies, clinicaltrials.gov
Despite their promise, JAK inhibitors come with substantial side effects that could complicate their use in treating alopecia areata. Regulators only cleared a lower, less effective dose of Lilly and Incyte's drug in 2018 due to safety concerns, and included a warning for blood clots, malignancy, and infections.
Post-marketing studies of Xeljanz, meanwhile, have identified higher rates of heart complications and cancer. Olumiant, Xeljanz, and AbbVie's Rinvoq all carry warnings on their prescribing information.
That profile — combined with the likely high cost — has caused some experts to express concern about using JAK inhibitors in alopecia areata. A 2019 editorial in the journal Lancet, for example, called for a "sober-risk-cost-benefit evaluation" of JAK inhibitors given the disease isn't life threatening.
"The understandable euphoria surrounding JAK inhibitors in the alopecia areata field must not blind one to potential risks," the authors wrote.
As the first to report Phase 3 results in alopecia areata, Lilly and Incyte could be the first to receive that evaluation.
The details of their results, however, will be crucially important. All that's known so far is that both doses tested — including the one approved in arthritis — met the study's main goal. No deaths, major cardiovascular events or blood clots were reported.
But it's unclear what percentage of patients responded, the magnitude of their response or how many of them had a 50% improvement in their so-called SALT score, a measure of hair loss. Lilly and Incyte are also looking at potential changes in patients' anxiety and depression after treatment, which could be important. Detailed data will be presented at a medical meeting this year.
"For patients who suffer from alopecia areata, it is not a cosmetic condition, it is a devastating autoimmune disease that can have significant psychological effects. They lose much more than just hair," said Lotus Mallbris, Lilly's vice president of immunology development, in a statement.
A second Phase 3 study is underway, with results expected in the first half of this year. Lilly has licensed rights to Olumiant from Incyte.