Breakthrough Clinical Results
Sun Pharma announced the launch of LEQSELVI™ (deuruxolitinib) in the United States for the treatment of adults with severe alopecia areata. LEQSELVI is an oral, selective Janus kinase (JAK) inhibitor that demonstrated rapid hair regrowth in clinical trials, with one-third of patients regaining almost all their hair within 24 weeks. The drug offers a new treatment option for this autoimmune disease, which can have a significant psychosocial impact on patients. Sun Pharma is committed to making LEQSELVI accessible through a support program offering reduced medication costs for eligible patients. The drug carries potential serious side effects, including infections, malignancies, and thrombosis, and should not be used in patients who are CYP2C9 poor metabolizers or taking certain inhibitors.
Key Highlights
- Launch of LEQSELVI™ (deuruxolitinib) in the U.S. for severe alopecia areata.
- Rapid hair regrowth demonstrated in clinical trials; one-third of patients regained almost all hair in 24 weeks.
- Provides a new treatment option for adults with severe alopecia areata.
- Sun Pharma's LEQSELVI SUPPORT™ Program offers reduced medication costs for eligible patients.
Incidence and Prevalence
Global Epidemiology of Alopecia Areata
Prevalence and Incidence
The general prevalence of alopecia is reported to be 1.02% according to a 2007 retrospective study. While this represents overall alopecia cases, more specific data is available from recent large-scale studies.
A 2022 Korean study represents one of the largest investigations into alopecia areata, comprising 73,107 patients with alopecia areata and 731,070 age- and sex-matched controls. Within this substantial cohort, 6,023 patients were diagnosed with more severe forms of the condition - alopecia totalis/universalis.
In the United States, a 2024 study utilizing the IBM MarketScan Research Database identified 45,483 individuals with alopecia areata between 2015 and 2020. This US cohort had a mean age of 43.8 years, with a notable gender disparity as 65.7% of patients were female.
It's worth noting that androgenetic alopecia represents the most common form of hair loss affecting both male and female populations, distinguishing it from alopecia areata.
Genetic Factors and Family History
A comprehensive 2024 meta-analysis included 67 studies encompassing 24,226 AA patients and their relatives, providing valuable insights into the genetic aspects of the condition.
This meta-analysis revealed that the prevalence of a family history of alopecia areata (AA) was 17.6% (CI: 14.9%-20.6%, I²=96%), indicating a significant genetic component to the disease.
The prevalence among relatives was 0.90% (CI: 0.55%-1.47%, I²=98%), with the highest prevalence observed in first-degree relatives at 3.22% (CI: 2.31%-4.48%, I²=94%). This gradient of prevalence based on relatedness further supports the genetic basis of alopecia areata.
Comorbidities
The 2024 meta-analysis also found that comorbid conditions were present in 9.61% (CI: 6.98%-13.1%, I²=95%) of family members across first-, second-, and third-degree relatives of individuals with alopecia areata.
These comorbidities included: - Thyroid disease (4.7%) - Diabetes (10.1%) - Atopic dermatitis (18.9%) - Vitiligo (5.5%) - Other autoimmune diseases (12.1%)
Clinical Variants
Alopecia areata incognita (AAI) represents a distinctive form of AA characterized by an acute onset resulting in sudden diffuse hair loss, differentiating it from the more common patchy presentation of alopecia areata.
Study Design Parameters
Study Design Parameters and Endpoints in Key Alopecia Areata Trials
Study Designs and Patient Selection
Various study designs have been employed in alopecia areata (AA) research, including:
- Cross-sectional design used in a 2008 study at the Department of Dermatology, Combined Military Hospital, Pakistan (2002-2004) with 50 consecutive patients
- Retrospective analytical reviews of scalp biopsies across multiple studies
- Comparative studies evaluating different biopsy techniques
- Post hoc analysis of the ALLEGRO-2b/3 trial (NCT03732807) examining longitudinal data from Weeks 24-48 with 650 participants
The ALLEGRO phase 2b/3 study investigated ritlecitinib in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. A total of 718 patients were randomized in this study. Patients received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg daily loading dose), 10 mg, or placebo for 24 weeks and then continued ritlecitinib or switched from placebo to ritlecitinib 200/50 or 50 mg for 24 weeks.
In a separate interventional study on tofacitinib, 50 patients of both genders diagnosed with AA, AT (alopecia totalis), and AU (alopecia universalis), aged five years to 50 years were included using a non-probability consecutive sampling technique.
Diagnostic Methods and Measured Parameters
Diagnostic approaches included: - 4mm punch biopsies commonly used across studies - Transverse and vertical sections of scalp biopsies compared for diagnostic accuracy - Dermatoscopy (magnification ×25 and ×60) used to evaluate 75 patients with AA - Paired biopsy specimens from haired areas versus areas with focal atrichia
Key measured parameters included: - Follicular unit counts and density/mm² - Terminal to vellus hair ratio - Anagen to telogen ratio - Cellular infiltrate and fibrosis - Telogen structures (mean count of 37%) - Dermatoscopic features: yellow dots (57.33%), black dots (84%), broken hairs (37.33%), short vellus hair (68%), tapering hair (18.67%)
Outcome Assessment Tools and Endpoints
The Severity of Alopecia Tool (SALT) score was a primary endpoint in multiple trials: - SALT20 (SALT score ≤20) and SALT10 (SALT score ≤10) were used to define responders in the ALLEGRO-2b/3 trial - Among 650 participants in ALLEGRO-2b/3, 114 (17.5%) were SALT20 responders - Of these, 76 (11.7%) were also SALT10 responders
For tofacitinib, treatment response was assessed at eight, 12, and 24 weeks using changes in the SALT score from baseline. The mean regrowth rate with tofacitinib was 88.9 ± 24.5%, with a statistically significant difference between baseline SALT scores and scores at eight, 12, and 24 weeks (p < 0.001).
Patient-reported outcomes (PROs) were also important endpoints: - The Alopecia Areata Patient Priority Outcomes (AAPPO) instrument was used in the ALLEGRO-2b/3 trial to evaluate improvement in hair loss, emotional symptoms (ES), and activity limitations (AL) from weeks 4 to 48 as a secondary endpoint - Studies demonstrated a positive relationship between scalp hair regrowth and downstream PROs - Improvements were measured in AA-related emotional symptoms, mental health, and work limitations
Statistical Analysis
Statistical methods included: - Chi-square test to assess statistical significance - Comparison of response proportions and mean changes from baseline - P-values reported for various associations (p=0.01 for follicular unit counts; p=0.0001 for telogen hair follicle counts)
The trials demonstrated an association between clinically meaningful hair regrowth and patient-reported treatment benefits, highlighting the importance of both clinical and patient-reported outcomes in AA research.
Drug used in other indications
Deuruxolitinib Clinical Trials
Based on the available information, there is no data regarding clinical indications beyond alopecia areata for which the JAK inhibitor deuruxolitinib (CTP-543) is currently undergoing clinical trials.
The only information available about deuruxolitinib relates to its use in treating alopecia areata, with noted side effects compared to placebo including:
- Headache: 21.4% vs 9.1% (OR = 2.7)
- Acne: 13.6% vs 4.5% (OR = 3.3)
- Nasopharyngitis: 14.6% vs 2.3% (OR = 7.3)
No information is available regarding intervention models, study designs, interventional protocols, or dosing regimens for deuruxolitinib trials in non-alopecia areata indications.