Deuruxolitinib Shows Efficacy in Hair Regrowth, Patient Satisfaction, and Psychosocial Wellbeing in Severe Alopecia Areata

Image credit: © DermNet

At the 33rd European Academy of Dermatology and Venereology (EADV) Congress held September 25 through 28 in Amsterdam, Netherlands, Sun Pharma presented 3 updates on deuruxolitinib (Lesqselvi) for the treatment of adults with severe alopecia areata. Deuruxolitinib, a JAK 1/2 inhibitor, was approved by the FDA on July 26, 2024, based on the results of 2 phase 3 clinical trials, THRIVE-AA1 (NCT04518995) and THRIVE-AA2 (NCT04797650), which together included 1220 patients with at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT).¹

Presentations at EADV 2024 included change in patient-reported hair satisfaction with deuruxolitinib, improvement in anxiety and depression in patients with severe alopecia, and the optimization of deuruxolitinib dosing in a phase 2 trial.^1-3

Change in Patient-Reported Hair Satisfaction During Deuruxolitinib Treatment of Severe Alopecia Areata: Pooled Data From the Phase 3 THRIVE-AA1 and THRIVE-AA2 Trials

THRIVE-AA1 and THRIVE-AA2 showed that 31% of patients treated with 8 mg of deuruxolitinib twice daily achieved a SALT score of ≤20 at 24 weeks, compared to 0.8% in the placebo group. Of these responders, 95.7% were satisfied with their hair by week 24. Hair satisfaction improvements were significant at week 12 (79.6%) and increased consistently through week 24, demonstrating a strong correlation between hair regrowth and patient satisfaction. Mirmirani et al concluded that deuruxolitinib significantly improves both hair regrowth and patient satisfaction, with statistically significant results (P < 0.0001).¹

Improvement in Anxiety and Depression in Adult Patients With Severe Alopecia Areata Treated With Deuruxolitinib: Pooled Data From the THRIVE-AA1 And THRIVE-AA2 Phase 3 Trials

Mostaghimi et al analyzed the impact of deuruxolitinib on anxiety and depression levels in severe alopecia areata patients using the Hospital Anxiety and Depression Scale (HADS). The pooled analysis from the THRIVE-AA1 and THRIVE-AA2 trials included 600 patients receiving 8 mg of deuruxolitinib twice daily and 267 patients receiving placebo. Results showed that 22.5% of the deuruxolitinib group achieved a ≥6-point improvement in the overall HADS score compared to 11.8% in the placebo group. Improvements were also seen in HADS-A (18.9% vs. 10.2%) and HADS-D (26.2% vs. 14.2%) scores, suggesting significant emotional benefits from the treatment (P < 0.05).²

Optimization of Deuruxolitinib Dosing in Adult Patients With Alopecia Areata: Results From a Randomized, Parallel-Group, Multicenter, Phase 2 Trial

A phase 2 study compared the efficacy and safety of deuruxolitinib8 mg twice daily versus 16 mg once daily in patients with severe alopecia areata. At week 24, patients receiving 8 mg twice daily had a greater mean relative reduction in SALT score (46.4%) compared to those receiving 16 mg once a day (18.0%). More patients in the 8 mg twice daily group achieved a 75% reduction in SALT score by week 24 (31.0% vs. 10.7%). Both dosing regimens were well-tolerated, with similar incidences of treatment-emergent adverse events (TEAEs), but no serious TEAEs were reported. The twice-daily dosing showed superior efficacy and was selected for phase 3 trials.³

Arash Mostaghimi, MD, MPH, MPA, recently spoke with Dermatology Times to provide more insight into the THRIVE-AA1 and THRIVE-AA2 trials and the significance of deuruxolitnib’s efficacy in patients with severe alopecia areata. Mostaghimi is a THRIVE-AA investigator and the vice chair of clinical trials and innovation and director of inpatient dermatology at Brigham and Women's Hospital in Boston, Massachusetts.

Q&A With Arash Mostaghimi, MD, MPH, MPA

Arash Mostaghimi, MD, MPH, MPA

Image credit: Sun Pharma

Dermatology Times: With numerous sessions and presentations on deuruxolitinib, what clinical points from THRIVE-AA1 and THRIVE-AA2 do you feel are most important for dermatology clinicians to be aware of regarding safety and efficacy?

Mostaghimi: The recent approval of deuruxolitinib provides physicians and patients with another effective treatment for severe alopecia areata. The data presented at EADV highlight the impact of deuruxolitinib not only to grow hair, but to achieve quality growth that increases patient-reported satisfaction with their hair. In addition, patients taking deuruxolitinib also had reductions in anxiety and depression over the course of their treatment, showing the impact of this drug on addressing the psychosocial impact of alopecia areata.

Dermatology Times: How does deuruxolitinib bring something new to the dermatologist’s armamentarium when treating alopecia areata?

Mostaghimi: Deuruxolitinib adds a new JAK inhibitor with proven safety and efficacy, giving physicians an additional choice for patients who are starting treatment or for those who have not responded to other therapies. Although no head-to-head studies between JAK inhibitors have been performed, deuruxolitinib’s data to date suggests that the time to response for patients taking deuruxolitinib may be among the fastest for JAK inhibitors in alopecia areata, giving those who are focused on getting better faster a strong option for care.

Dermatology Times: How significantly did anxiety and depression improve in adult patients who were treated with deuruxolitinib in THRIVE-AA1 and THRIVE-AA2?

Mostaghimi: Of 600 patients taking deuruxolitinib, 22.5% demonstrated a clinically significant (≥6-point improvement) in the overall HADS score from baseline to Week 24 vs 11.8.% of 267 placebo-treated patients over the 24-week study. Subscales showed improvement for both depression and anxiety.

Dermatology Times: What patient characteristics do you consider before selecting deuruxolitinib as a treatment option?

Mostaghimi: Prior to starting treatment with deuruxolitinib, physicians should make sure to have a conversation with patients about the safety and efficacy of the medication. Like other JAK inhibitors,deuruxolitinib has a black-box warning for venous thromboembolism (VTE), and although there are no strict contraindications, an evaluation of the patient’s other risk factors for VTE including obesity, history of clot, smoking, and use of estrogen-containing oral contraceptive agents should be made to risk-stratify patients. Patients must also be able and willing to consistently take a twice daily medication.

References

1. U.S. FDA approves LEQSELVI (deuruxolitinib), an oral jak inhibitor for the treatment of severe alopecia areata. News release. Sun Pharmaceutical Industries Limited. July 26, 2024. Accessed September 27, 2024. https://www.prnewswire.com/news-releases/us-fda--approves-leqselvi-deuruxolitinib-an-oral-jak-inhibitor-for-the-treatment-of-severe-alopecia-areata-302207222.html?tc=eml_cleartime
2. Mirmirani P, Mesinkovska N, King B, et al. Change in patient-reported hair satisfaction during deuruxolitinib treatment of severe alopecia areata: Pooled data from the Phase 3 THRIVE-AA1 and THRIVE-AA2 trials. Presented at: 33rd European Academy of Dermatology and Venereology Congress; September 25-28, 2024; Amsterdam, Netherlands
3. Mostaghimi A, King B, Senna M, et al. Improvement in anxiety and depression in adult patients with severe alopecia areata treated with deuruxolitinib: Pooled data from the THRIVE-AA1 and THRIVE-AA2 phase 3 trials. Poster presented at: 33rd European Academy of Dermatology and Venereology Congress; September 25-28, 2024; Amsterdam, Netherlands
4. King B, Kempers S, Mesinkovska N, et al. Optimization of deuruxolitinib dosing in adult patients with alopecia areata: Results from a randomized, parallel-group, multicenter, phase 2 trial. Poster presented at: 33rd European Academy of Dermatology and Venereology Congress; September 25-28, 2024; Amsterdam, Netherlands