How were the trials designed?

The efficacy and safety of LITFULO were evaluated in a randomized, double-blind, placebo controlled trial in 718 patients 12 years of age and older with alopecia areata with ≥50% scalp hair loss, including alopecia totalis and alopecia universalis.

The trial randomized patients to one of the following treatment regimens for 48 weeks: 1) LITFULO 200 mg once daily for 4 weeks followed by 50 mg once daily for 44 weeks (132 patients); 2) LITFULO 200 mg once daily for 4 weeks followed by 30 mg once daily for 44 weeks (130 patients); 3) LITFULO 50 mg once daily for 48 weeks (130 patients); 4) LITFULO 30 mg once daily for 48 weeks (132 patients); 5) LITFULO 10 mg once daily for 48 weeks (63 patients); 6) placebo for 24 weeks followed by LITFULO 200 mg once daily for 4 weeks and 50 mg once daily for 20 weeks (65 patients); or 7) placebo for 24 weeks followed by LITFULO 50 mg once daily for 24 weeks (66 patients). Safety was also evaluated in two placebo-controlled trials in which patients were randomized to LITFULO 200 mg once daily for four weeks followed by 50 mg once daily (80 patients) or placebo (82 patients).

The safety evaluation was also supported by two randomized placebo-controlled trials in which 80 patients were randomized to LITFULO 200 mg once daily for 4 weeks followed by 50 mg once daily and 82 patients were randomized to placebo for 24 weeks.

Assessment of scalp hair loss was based on SALT score. SALT scores range from 0 to 100 with 0 = no scalp hair loss and 100 = total scalp hair loss. The primary endpoint was the proportion of patients with SALT ≤20 response (20% or less of scalp hair loss) at Week 24 and the secondary endpoint was the proportion of patients with SALT ≤10 response (10% or less of scalp hair loss) at Week 24.

Who participated in the trials?

Table 1 summarizes the demographics in the trial.

Table 1. Trial Demographics

Source: Adapted from FDA Review
*Includes American Indian or Alaskan Native, Native Hawaiian or Other Pacific Islander, multiracial, and race not reported

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 2 summarizes the efficacy results for the patients evaluated in a clinical trial for LITFULO. Assessment of scalp hair loss was based on SALT score. SALT scores range from 0 to 100 with 0 = no scalp hair loss and 100 = total scalp hair loss. At Week 24, a greater proportion of subjects had a SALT ≤20 response (20% or less of scalp hair loss) and SALT ≤10 response (10% or less of scalp hair loss) with LITFULO compared to placebo.

Table 2. Summary of Sitting FVC in Adults With LOPD by ERT Status at 52 Weeks in Trial 1

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; SALT, Severity of Alopecia Tool

Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?

Table 3. SALT ≤20 at Week 24 by Subgroup

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; NA, not applicable

What are the possible side effects (results of trials used to assess safety)?

Adverse events reported in ≥1% of patients treated with LITFULO and more common than patients treated with placebo up to Week 24 are listed Table 4.

Table 4. Adverse Reactions in Clinical Trials of LITFULO for the Treatment of Alopecia Areataa

Source: LITFULO Prescribing Information
^a Reported in ≥1% of subjects and at a higher rate than placebo for up to 24 weeks.
^b Headache includes headache and migraine.
^c Diarrhea includes diarrhea and frequent bowel movements.
^d Acne includes acne and acne pustular.
^e Rash includes rash and dermatitis allergic.

Were there any differences in side effects of the clinical trials among sex, race and age groups?

The overall safety database and individual subgroup sample sizes were not sufficient to detect clinically meaningful differences in the frequency of treatment-emergent adverse events (TEAEs) between individual subgroups.

Age subgroup: No clinically meaningful differences between the adverse event (AE) profiles for adolescent and adult subjects were identified. A trend towards a higher frequency of reported TEAEs (urinary tract infection, lymphocyte count decreased, arthralgia, and herpes zoster), severe AEs, serious adverse events (SAEs) (including serious infections), AE leading to discontinuations (AELD)s, and adjudicated AEs of malignancy (excluding nonmelanoma skin cancer and basal cell carcinoma) in subjects ≥65 years of age, compared to adult subjects (≥18 years of age) were reported for the all-exposure pool.

Sex subgroup: Female subjects were reported with a higher frequency of TEAEs and with similar frequency for severe AEs, SAEs, AELDs, and adverse reactions (related) (ARs) than male subjects in their corresponding LITFULO dose groups (and placebo group). No clinically meaningful differences between the AE profiles for male and female subjects were identified (including safety AEs of interest). Headache and urinary tract infections were higher, and blood creatine phosphokinase increased lower in female patients.

Race and ethnicity subgroups: Subgroup analysis by race included only White and Asian subjects due to limited number of subjects in other race groups. Asian subjects were reported with a higher frequency of upper respiratory tract infections, folliculitis, and urticaria in the LITFULO 50 mg dose group. Hispanic or Latino subjects compared to not Hispanic or Latino subjects showed more frequent TEAEs in the all-exposure pool.

Table 5. Proportion of Subjects With Treatment-Emergent Adverse Events by Subgroup Through Week 24

Source: Adapted from FDA Review
Abbreviations: n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm