Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting.
In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of ≤20 ― which indicates that hair regrowth has occurred on at least 80% of the scalp ― was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.
In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of ≤20 by 24 months.
These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who co-chaired the late-breaking session in which the study findings were discussed.
THRIVE-AA1 only included patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25% to 50% at enrollment.
Moreover, “very stringent criteria” were used. SALT scores of ≤10 were evaluated in both studies, observed Samimi, professor of dermatology at the University of Tours in France.
“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Samimi added.
Deuruxolitinib and the THRIVE Trials
Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.
Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1200 patients.
Results of THRIVE-AA1 have been reported by the manufacturer, and Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven Connecticut, presented a more comprehensive review at the EADV meeting.
He reported that at 24 weeks, SALT scores of ≤20 were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was only seen in 1% of the placebo-treated patients.
The more stringent endpoint of having a SALT score of ≤10, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.
“This is truly transformative therapy,” King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.
There were reasonably high rates of patient satisfaction with the treatment, according to King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.
Safety was as expected, and there were no signs of any blood clots, said King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, vs 2.9% of those who received placebo.
Overall, the results look promising for deuruxolitinib, he added. He noted that that almost all patients included in the trial have opted to continue in the open-label long-term safety study.
Prescribing information of the JAK inhibitors approved by the US Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.
Ritlecitinib and the ALLEGRO Studies
Interim results of the ongoing, open-label, phase 3 ALLEGRO-LT study with ritlecitinib were presented separately by Athanasios Tsianakas, MD, head of the Department Of Dermatology at Fachklinik Bad Bentheim, Germany.
Ritlecitinib, which targets JAK3 and also the TEC family of tyrosine kinases, had met all of its endpoints in the prior ALLEGRO Phase 2b/3 study, Tsianakas said. Those included the benchmarks of a SALT score of ≤20 and a SALT score of ≤10.
“Ritlecitinib showed a very good long-term efficacy and good safety profile in our adolescent and adult patients suffering from alopecia areata,” said Tsianakas.
A total of 447 patients were included in the trial. They were treated with 50 mg of ritlecitinib every day; some had already participated in the ALLEGRO trial, while others had been newly recruited. The latter group entered the trial after a 4-week run-in period, during which a 200-mg daily loading dose was given for 4 weeks.
Most (86%) patients had been exposed to ritlecitinib for at least 12 months; one fifth had discontinued treatment at the data cutoff, generally because the patients no longer met the eligibility criteria for the trial.
Safety was paramount, Tsianakas highlighted. There were few adverse events that led to temporary or permanent discontinuation of the study drug. The most common TEAEs that affected 5% or more of patients included headache and acne. There were two cases of MACE (one nonfatal myocardial infarction and one nonfatal stroke).
The proportion of patients with a SALT score of ≤20 was 2.5% at 1 month, 27.9% at 3 months, 50.1% at 6 months, 59.8% at 9 months, and 65.5% at 12 months. Thereafter, there was little shift in the response. A sustained effect, in which a SALT score of ≤20 was seen out to 24 months, occurred in 69.9% of patients.
A similar pattern was seen for SALT scores of ≤10, ranging from 16.5% at 3 months to 62.5% at 24 months.
Following in Baricitinib’s Footsteps?
This not the first time that JAK inhibitors have been shown to have beneficial effects for patients with AA. Baricitinib (Olumiant) recently became the first JAK inhibitor to be granted marketing approval for AA in the United States, largely on the basis of two pivotal phase 3 studies, BRAVE-AA1 and BRAVE-AA2.
“This is just such an incredibly exciting time,” said King. “Our discoveries in the lab are being translated into effective therapies for patients with diseases for which we’ve not previously had therapies,” he commented.
“Our concept of interferon gamma– and interleukin-15–mediated disease is probably not true for everybody,” King said, who acknowledged that some patients with AA do not respond to JAK inhibitor therapy or may need additional or alternative treatment.
“It’s probably not that homogeneous a disease,” he added. “It’s fascinating that the very first drugs for this disease are showing efficacy in as many patients as they are.”
The THRIVE-AAI study was funded by CONCERT Pharmaceuticals. King has served on advisory boards, has provided consulting services to, or has been a trial investigator for multiple pharma companies, including CoNCERT Pharmaceuticals. The ALLEGRO-LT study was funded by Pfizer. Tsianakas has acted as a clinical trial investigator and speaker for Pfizer.
European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting: Late-breaking Abstracts 3473 and 3454. Presented September 10, 2022.
Sara Freeman is a freelance journalist based in London, England.
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