Ruxolitinib data positive for efficacy, safety

May 22, 2020

Ruxolitinib met primary and secondary endpoints in the phase 3 TRueE-AD1 and TRuE-AD2 studies, underscoring the idea that the disruption of multiple cytokine networks simultaneously is a promising treatment approach.

Topical selective Janus kinase (JAK1/JAK2) inhibitor ruxolitinib cream (Jakafi, Incyte) demonstrated safety and efficacy in phase 2 and 3 clinical trials examining its use in the treatment atopic dermatitis and itch.

Ruxolitinib is currently in phase 3 development for the treatment of adults with atopic dermatitis as well as for adolescents and adults with vitiligo. The drug met primary and secondary endpoints in the phase 3 TRueE-AD1 and TRuE-AD2 studies looking at nearly 1,250 patients ages 12 years and older with mild-to-moderate atopic dermatitis, according to a press release from Incyte.1

The disruption of multiple cytokine networks simultaneously is a promising treatment approach for atopic dermatitis, researchers reported in phase 2 ruxolitinib study published February 1, 2020 in the Journal of Allergy and Clinical Immunology.2

“JAK inhibitors provide the opportunity to impair multiple cytokine pathways simultaneously and are approved for the treatment of several diseases, including rheumatoid arthritis…,” the author wrote.

Applied topically, ruxolitinib directly targets different pathogenic pathways that underlie atopic dermatitis, they wrote.

Phase 2 key findings

The phase 2 randomized, double-blind, dose ranging, vehicle-and active-controlled study of 307 adult patients with mild-to-moderate atopic dermatitis compared different strengths of ruxolitinib to the mid-potency steroid triamcinolone and vehicle. They found that ruxolitinib concentrations of 0.5% once daily and 0.15% once daily, 1.5% once daily and 1.5% twice daily, all resulted in increasing improvement in symptoms with higher concentrations. The 1.5% concentration of the topical applied twice daily resulted in the greatest improvement, with a 71.6% improvement from baseline to four weeks in the Eczema Area and Severity Index (EASI) compared to 15.5% in the vehicle group.
Both 1.5% ruxolitinib once daily and twice daily groups had greater improvement in the EASI compared to triamcinolone treatment at four weeks, but the differences were not statistically significant, according to the phase 2 study.

Another key finding from the trial was a notable and lasting improvement in itch among those treated with ruxolitinib at all strengths.
“… for 1.5% [ruxolitinib cream twice daily] significant improvement in itch was observed within 36 hours of treatment,” the authors wrote. 

When researchers measured improvements in itch using a numerical rating scale and quality of life (QoL) with the Skindex-16, they found overall that 42.5% of patients who applied 1.5% ruxolitinib twice daily experienced minimal clinically important difference in itch within 36 hours of treatment, compared to 13.6% of those in the vehicle group.
“…near-maximal improvement was observed by week four. Itch reduction was associated with improved QoL burden …. Significant improvements in Skindex-16 overall scores were noted at week two,” according to a related study by many of the same authors published in the Journal of the American Academy of Dermatology (JAAD).3

Phase 3 findings

Phase 3 trial researchers studied patients with an Investigator’s Global Assessment (IGA) score of 2 to 3, and atopic dermatitis on 3% to 20% of their body surface area, except the scalp. They randomly assigned patients to eight-weeks of treatment with ruxolitinib cream 0.75% administered twice daily, ruxolitinib cream 1.5% twice daily or vehicle cream.
Among the key findings in TRuE AD1:

  • Fifty percent of patients in the ruxolitinib cream 0.75% group and 53.8% of those in the ruxolitinib group achieved an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a two-point improvement from baseline at week eight, compared to 15.1% in the control group.

  • Fifty-six percent of patients treated with ruxolitinib cream 0.75% and 62.1% of patients in the ruxolitinib cream 1.5% group achieved 75% improvement or more in EASI score compared to baseline, compared to 24.6% in those in the vehicle control group.

Researchers reported in TRuE-AD2 that 39.0% of patients treated with ruxolitinib cream 0.75% and 51.3% of those treated 1.5% achieved an IGA score of 0 or 1 with at least a two-point improvement from baseline at week eight, compared to 7.6% treated with vehicle cream. More than 51% of patients in the 0.75% group and 61.8% of those in the 1.5% group achieved 75% improvement or more in the EASI score from baseline, compared to 14.4% treated with vehicle, according to the press release.

Researchers of both phase 3 trials also found a statistically significant reduction of itch at both dosages of ruxolitinib cream compared to vehicle control.
Patients experienced comparable rates of treatment emergent adverse events in all three groups, according to the release.

Disclosures:

Incyte funded the research on ruxolitinib for atopic dermatitis. Authors on the phase 2 published studies include people who have ties to Incyte. Some are company employees and shareholders.

References:

1 Incyte Announces Positive Topline Results From Phase 3 TRuE-AD Program Evaluating Ruxolitinib Cream in Patients With Atopic Dermatitis. February 2020. Available here. Accessed May 2020.

2 Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME; INCB 18424-206 Study Investigators. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020 Feb;145(2):572-582.

3 Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study. J Am Acad Dermatol. 2020 Feb 11. pii: S0190-9622(20)30213-9.