ALLEGRO-2b/3 Study Overview

Study Design

Baseline Characteristics

Key Study Endpoints

Tab Number 4

Tab Number 5

The efficacy and safety of LITFULO were evaluated in the pivotal study, ALLEGRO-2b/3[1-3]

ALLEGRO-2b/3 was a randomised, double-blind, placebo-controlled, phase 2b/3 study in patients, aged 12 years and older (N=718), with alopecia areata and 50% or more scalp hair loss, including AT and AU. Patients were randomised to receive ritlecitinib or placebo once-daily for 24 weeks. After 24 weeks, all patients received ritlecitinib and there was no placebo control.[2]^†

Illustration made by Pfizer based on ref. 2 figure 1

The primary endpoint was the proportion of patients with SALT score ≤10 at Week 24[2]  
The key secondary endpoint was the proportion of patients with a PGI-C response of “moderately” or “greatly” improved at Week 24[2]^‡
Safety was monitored throughout the study[2]  
Efficacy results include patients who received LITFULO 50 mg (the approved daily dose)[1]

The sample size for this study accounted for multiplicity using a closed testing procedure at Week 24 to ensure control of Type 1 error for all comparisons between active treatment groups and placebo.

The Patient's Global Impression of Change (PGI-C) is a self-administered questionnaire that asks patients to evaluate the improvement or worsening of their alopecia areata as compared to the start of the study. Responses of “moderately” or “greatly” improved were used as the patient-driven responder definition.

What is SALT?

The Severity of Alopecia Tool (SALT) helps visually assess the extent of scalp hair loss.[1,4,5]

The SALT score equals the sum of the proportions of scalp hair loss per quadrant[4]

The SALT score measures hair loss on a scale of 0 (no scalp hair loss) to 100 (complete scalp hair loss). For example, SALT 10 can be defined as 10% scalp hair loss and/or 90% scalp hair coverage[1,2]

AT=alopecia totalis; AU=alopecia universalis; SALT=Severity of Alopecia Tool.

References:

1. LITFULO (ritlecitinib) SmPC. 2. King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial. Lancet. 2023;401(10387):1518-1529. doi:10.1016/S0140-6736(23)00222-2. Erratum in: Lancet. 2023 Jun 10; 401(10392):1928. 3.King B, Zhang X, Harcha WG, et al. Supplement to: Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial. Lancet. April 13, 2023. doi:10.1016/S0140-6736(23)00222-2. 4.Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines part II. J Am Acad Dermatol. 2004;51(3):440-447. doi:10.1016/j.jaad.2003.09.032 5.Olsen EA, Canfield D. SALT Il: a new take on the Severity of Alopecia Tool (SALT) for determining percentage scalp hair loss. J Am Acad Dermatol. 2016;75(6):1268-1270. doi:10.1016/j.jaad.2016.08.042.

Selected baseline characteristics

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	LITFULO 50 mg (n=130)	Placebo (n=131)
Age, n (%)
12 to 17 years	18 (14)	19 (15)
≥18 years	112 (86)	112 (86)
Female, n (%)	71 (55)	86 (66)
Race, n (%)
White	79 (61)	94 (72)
Black or African American	5 (4)	4 (3)
Asian	43 (33)	31 (24)
AT/AU, n (%)	60 (46)	60 (46)
Mean SALT score (SD)	90.3 (14.7)	93 (11.5)
Mean non-AT/AU SALT score (SD)	82 (15.9)	87 (12.9)
Abnormal eyebrows, n (%)	106 (82)	107 (82)
Abnormal eyelashes, n (%)	95 (73)	97 (74)
Mean duration since diagnosis, years (SD)	8.7 (8.7)	11 (11.8)
Mean duration of current episode, years (SD)	3.2 (2.7)	3.2 (2.7)

Table made by Pfizer based on ref. 2 table 1

Key Inclusion Criteria[1-3]

Male and female patients, 12 years of age or older*
Clinical diagnosis of alopecia areata
50% or more scalp hair loss, including alopecia totalis or alopecia universalis
No evidence of terminal hair regrowth within 6 months, assessed at both the screening and baseline visits
Current episode of hair loss <10 years

Key Exclusion Criteria[2,3]

Other types of alopecia
Previous use of any JAK inhibitor
Any psychiatric condition, including clinically significant depression
Auditory conditions considered acute, fluctuating, or progressive
History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localised, dermatomal herpes zoster
Patients aged 12 to <18 years without a documented history of varicella-zoster virus vaccination or presence of varicella-zoster virus IgG antibodies

Within Voluntary Harmonisation Procedure countries in the European Union, patients had to be between 18 and 74 years of age.

What is SALT?

The Severity of Alopecia Tool (SALT) helps visually assess the extent of scalp hair loss.[1,4,5]

The SALT score equals the sum of the proportions of scalp hair loss per quadrant[4]

Illustration made by Pfizer based on images in ref. 4

Illustration made by Pfizer based on data and images in ref. 4

AT=alopecia totalis; AU=alopecia universalis; IgG=immunoglobulin; JAK=Janus kinase; SALT=Severity of Alopecia Tool; SD=standard deviation.

References:

1.LITFULO (ritlecitinib) SmPC. 2.King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial. Lancet. 2023;401(10387):1518-1529. doi:10.1016/S0140-6736(23)00222-2. Erratum in: Lancet. 2023 Jun 10; 401(10392):1928. 3.King B, Zhang X, Harcha WG, et al. Supplement to: Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b–3 trial. Lancet. April 13, 2023. doi:10.1016/S0140-6736(23)00222-2. 4.Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines part II. J Am Acad Dermatol. 2004;51(3):440-447. doi:10.1016/j.jaad.2003.09.032 5.Olsen EA, Canfield D. SALT Il: a new take on the Severity of Alopecia Tool (SALT) for determining percentage scalp hair loss. J Am Acad Dermatol. 2016;75(6):1268-1270. doi:10.1016/j.jaad.2016.08.042.

Key study endpoints[1-3]

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Primary endpoint	For the EMA: Proportion of patients with a SALT score ≤10 (≥90% scalp hair coverage) vs placebo at Week 24*  For Overall study and FDA: The proportion of patients with SALT ≤20 (≥80% scalp hair coverage) at Week 24^†
Key secondary endpoint	For the EMA: Proportion of patients with a PGI-C score of "moderately" or "greatly" improved at Week 24^‡
Additional secondary endpoints	Proportion of patients with a SALT score ≤10 (≥90% scalp hair coverage) through Week 48 Proportion of patients with a SALT score ≤20 (≥80% scalp hair coverage) through Week 48 Proportion of patients with ≥2-grade improvement from baseline, or with a score of 3, in eyebrows and eyelashes through Week 48

Primary endpoint

For the EMA: Proportion of patients with a SALT score ≤10 (≥90% scalp hair coverage) vs placebo at Week 24* 
For Overall study and FDA: The proportion of patients with SALT ≤20 (≥80% scalp hair coverage) at Week 24^†

Key secondary endpoint

For the EMA: Proportion of patients with a PGI-C score of "moderately" or "greatly" improved at Week 24^‡

Additional secondary endpoints

Proportion of patients with a SALT score ≤10 (≥90% scalp hair coverage) through Week 48

Proportion of patients with a SALT score ≤20 (≥80% scalp hair coverage) through Week 48

Proportion of patients with ≥2-grade improvement from baseline, or with a score of 3, in eyebrows and eyelashes through Week 48

Table made by Pfizer based on data in ref. 1-3

Based on a preestablished testing procedure at an overall significance level (α=0.01).

Based on a preestablished testing procedure at an overall significance level for the overall study (α=0.05) and the FDA (α=0.00125).

The Patient’s Global Impression of Change (PGI-C) is a self-administered questionnaire that asks the subject to evaluate the improvement or worsening of their alopecia areata as compared to the start of the study. Responses of “moderately” or “greatly” improved were used as the patient-driven responder definition.

EMA=European Medicines Agency; FDA=Food and Drug Administration; SALT=Severity of Alopecia Tool.

References: