LITFULO

LITFULO (ritlecitinib) capsules are formulated with ritlecitinib tosylate, a kinase inhibitor. Ritlecitinib tosylate is a white to off white to pale pink solid which is freely soluble in water. The chemical name is 1-{(2S,5R)-2-Methyl-5-[(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}prop-2-en-1-one 4 methylbenzene-1-sulfonic acid. The molecular formula for ritlecitinib tosylate is C 22 H 27 N 5 O 4 S. The molecular weight is 457.55 g/mol and its structural formula is: LITFULO is supplied for oral administration as a 50 mg immediate-release capsule. Each capsule contains 50 mg ritlecitinib (equivalent to 80.13 mg ritlecitinib tosylate) and the following inactive ingredients: crospovidone, glyceryl dibehenate, lactose monohydrate, microcrystalline cellulose, and hypromellose (HPMC) capsule shells. The yellow/blue, opaque capsule shells contain Brilliant blue FCF – FD&C Blue, hypromellose, titanium dioxide, and yellow iron oxide. Chemical Structure

LITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Limitations of Use : Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants. LITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. ( 1 ) Limitations of Use : Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants ( 1 ).

• For recommended testing, evaluations and immunizations prior to LITFULO initiation, see Full Prescribing Information. ( 2.1 ) • Recommended dosage is 50 mg orally once daily. ( 2.2 ) • For dosage interruption for certain adverse reactions, see Full Prescribing Information. ( 2.4 ) 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Perform the following evaluations prior to LITFULO initiation: • Tuberculosis (TB) infection evaluation: LITFULO initiation is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk for TB, start preventive therapy for latent TB prior to initiation of LITFULO [see Warnings and Precautions (5.1) ] . • Viral hepatitis screening in accordance with clinical guidelines: LITFULO initiation is not recommended in patients with hepatitis B or hepatitis C [see Warnings and Precautions (5.1) ] . • Treatment with LITFULO should not be initiated in patients with an absolute lymphocyte count (ALC) <500/mm 3 or a platelet count <100,000/mm 3 [see Warnings and Precautions (5.7) ] . • Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.8) ] . 2.2 Recommended Dosage The recommended dosage of LITFULO is 50 mg orally once daily with or without food [see Clinical Pharmacology (12.3) ] . Swallow capsules whole. Do not crush, split, or chew LITFULO capsules. If a dose is missed, administer the dose as soon as possible unless it is less than 8 hours before the next dose, in which case, skip the missed dose. Thereafter, resume dosing at the regular scheduled time. 2.3 Patients with Severe Hepatic Impairment LITFULO is not recommended in patients with severe (Child Pugh C) hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 2.4 Treatment Interruption or Discontinuation If treatment interruption is indicated, a temporary treatment interruption for less than 6 weeks is not expected to result in significant loss of regrown scalp hair. Hematologic Abnormalities Recommendations for LITFULO treatment interruption or discontinuation for hematologic abnormalities are summarized in Table 1. Table 1. Laboratory Monitoring Guidance Laboratory Measure Recommendation ALC = absolute lymphocyte count. Platelet Count Treatment should be discontinued if platelet count is <50,000/mm 3 Lymphocytes Treatment should be interrupted if ALC is <500/mm 3 and may be restarted once ALC return above this value. ALC and platelet counts are recommended before treatment initiation and at 4 weeks after treatment initiation, and thereafter according to routine patient management [see Warnings and Precautions (5.7) ] .

LITFULO is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients [see Warnings and Precautions (5.6) ] . LITFULO is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients. ( 4 )

The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious Infections [see Warnings and Precautions (5.1) ] • Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3) ] • Thromboembolic Events [see Warnings and Precautions (5.5) ] • Hypersensitivity [see Warnings and Precautions (5.6) ] • Laboratory Abnormalities [see Warnings and Precautions (5.7) ] Most common adverse reactions (incidence ≥1%) are headache, diarrhea, acne, rash, urticaria, folliculitis, pyrexia, atopic dermatitis, dizziness, blood creatine phosphokinase increased, herpes zoster, red blood cell count decreased, and stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of LITFULO was evaluated in three randomized, placebo-controlled clinical trials and one long-term trial in subjects with alopecia areata, including alopecia totalis and alopecia universalis, who were 12 years of age and older. A total of 1628 subjects were treated with LITFULO representing 2085 subject-years of exposure. There were 1011 subjects with at least 1 year of exposure to LITFULO. In the placebo-controlled period of clinical trials in alopecia areata, a total of 668 subjects were exposed to LITFULO with 130 receiving 50 mg once daily for up to 24 weeks. The median age of subjects was 33 years, 105 (11.9%) subjects were 12 to <18 years old and 22 (2.5%) subjects were 65 years of age or older. The majority of subjects were White (70.7%) and female (63.6%). Adverse reactions occurring at ≥1% in the treated groups and at a higher rate than placebo are presented in Table 2. A total of 2 (1.5%) subjects treated with LITFULO 50 mg were discontinued from the trials due to adverse reactions. Table 2. Adverse Reactions in Clinical Trials of LITFULO for the Treatment of Alopecia Areata Reported in ≥1% of subjects and at a higher rate than placebo for up to 24 weeks. LITFULO 50 mg N=130 n (%) Placebo N=213 n (%) Headache Headache includes headache and migraine. 14 (10.8) 18 (8.5) Diarrhea Diarrhea includes diarrhea and frequent bowel movements. 13 (10.0) 8 (3.8) Acne Acne includes acne and acne pustular. 8 (6.2) 10 (4.7) Rash Rash includes rash and dermatitis allergic. 7 (5.4) 2 (0.9) Urticaria 6 (4.6) 3 (1.4) Folliculitis 4 (3.1) 4 (1.9) Pyrexia 4 (3.1) 0 Dermatitis atopic 3 (2.3) 1 (0.5) Dizziness 3 (2.3) 3 (1.4) Blood creatine phosphokinase increased 2 (1.5) 0 Herpes zoster 2 (1.5) 0 Red blood cell count decreased 2 (1.5) 0 Stomatitis 2 (1.5) 0 Specific Adverse Reactions Exposure adjusted incidence rates were adjusted by clinical trial size for all adverse reactions reported in this section. Overall Infections In the placebo-controlled trials, for up to 24 weeks, overall infections were reported in 66 subjects (80.35 per 100 subject-years) treated with placebo and 43 subjects (74.53 per 100 subject-years) treated with LITFULO 50 mg. Across clinical trials, including the long-term trial, overall infections were reported in 645 subjects (50.71 per 100 subject-years) treated with LITFULO 50 mg or higher. Serious Infections In the placebo-controlled trials, for up to 24 weeks, 3 subjects reported serious infections across all ritlecitinib doses studied. Across clinical trials, including the long-term trial, serious infections were reported in 12 subjects (0.66 per 100 subject-years) treated with LITFULO 50 mg or higher. The most common serious infections were related to appendicitis, COVID-19 infection (including pneumonia), and sepsis. Herpes Zoster In the placebo-controlled trials, for up to 24 weeks, herpes zoster was reported in 4 subjects across all ritlecitinib doses studied and 0 subjects treated with placebo. Across clinical trials, including the long-term trial, herpes zoster was reported in 21 subjects (1.17 per 100 subject-years) treated with LITFULO 50 mg or higher. Opportunistic infections of multi-dermatomal herpes zoster were reported in 1 subject (0.50 per 100 subject-years) treated with the ritlecitinib higher dose in the placebo-controlled trials and 2 subjects (0.1 per 100 subject-years) treated with LITFULO 50 mg or higher in all clinical trials. Malignancy In the placebo-controlled trials, for up to 24 weeks, 1 malignancy (breast cancer) was reported in 1 subject (1.33 per 100 subject-years) treated with ritlecitinib higher dose and no malignancy was reported in subjects treated with placebo. Across clinical trials, including the long-term trial, malignancies excluding NMSC were reported in 7 subjects (0.37 per 100 subject-years) treated with LITFULO 50 mg or higher. Thromboembolic Events Across clinical trials, including the long-term trial, pulmonary embolism (PE) was reported in 1 subject (0.06 per 100 subject-years) treated with LITFULO. There was 1 report of retinal artery occlusion and 1 report of acute myocardial infarction. Urticaria In the placebo-controlled trials, for up to 24 weeks, urticaria was reported in 28 subjects treated in all ritlecitinib doses studied and 3 subjects treated with placebo. The rate of urticaria was 8.23 per 100 subject-years in subjects treated with ritlecitinib 50 mg and 4.03 per 100 subject-years in subjects treated with placebo. Across clinical trials, including the long-term trial, urticaria was reported in 76 subjects treated with LITFULO 50 mg or higher. Among all subjects treated with ritlecitinib 50 mg or higher in the integrated safety analysis, the rate of urticaria was 4.10 per 100 subject-years. The median time to onset of an initial event was 8 weeks; median duration of urticaria was 7 days. Most of the cases were mild to moderate in severity. Decreased Lymphocyte Counts Across clinical trials, including the long-term trial confirmed ALC <500/mm 3 occurred in 1 subject (<0.1%) treated with LITFULO 50 mg. Age appeared to be a risk factor for lower ALC in subjects ≥65 years of age. Decreased Platelet Count In the placebo-controlled trials, for up to 24 weeks, treatment with LITFULO was associated with a decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which platelet count remained stable at a lower level with continued therapy. Across clinical trials, including the long-term trial, 1 subject (<0.1%) had a confirmed platelet count <100,000/mm 3 . No subject had a confirmed platelet count <75,000/mm 3 . Creatine Phosphokinase (CPK) Elevations In the placebo-controlled trials, for up to 24 weeks, events of blood CPK increased were reported in 2 (1.5%) subjects treated with LITFULO 50 mg and 0 subjects treated with placebo. Liver Enzyme Elevations In the placebo-controlled trials, for up to 24 weeks, events of increases in liver enzymes ≥3 times the upper limit of normal (ULN) were observed in subjects treated with LITFULO [see Warnings and Precautions (5.7) ] .

• Certain CYP3A substrates: Additional monitoring and dose adjustment of CYP3A substrate should be considered. ( 7.1 ) • Certain CYP1A2 substrates: Additional monitoring and dose adjustment of CYP1A2 substrate should be considered. ( 7.1 ) • Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended. ( 7.2 ) 7.1 Effects of LITFULO on Other Drugs Table 3 includes clinically significant drug interactions affecting other drugs. Table 3. Clinically Significant Interactions Affecting Other Drugs CYP3A Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP3A inhibitor. Concomitant use of ritlecitinib increases AUC and C max of CYP3A substrates [see Clinical Pharmacology (12.3 )] , which may increase the risk of adverse reactions of these substrates. Intervention Consider additional monitoring and dosage adjustment in accordance with approved product labeling of CYP3A substrates where small concentration changes may lead to serious adverse reactions when used with LITFULO. CYP1A2 Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP1A2 inhibitor. Concomitant use of ritlecitinib increases AUC and C max of CYP1A2 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of these substrates. Intervention Consider additional monitoring and dosage adjustment in accordance with the approved product labeling of CYP1A2 substrates where small concentration changes may lead to serious adverse reactions when used concomitantly with LITFULO. 7.2 Effects of Other Drugs on LITFULO Table 4 includes clinically significant drug interactions affecting LITFULO. Table 4. Clinically Significant Interactions Affecting LITFULO CYP3A Inducers Clinical Impact Concomitant use of strong CYP3A inducer (e.g., rifampin) may decrease AUC and C max of ritlecitinib [see Clinical Pharmacology (12.3) ] , which may result in loss of or reduced clinical response. Intervention Coadministration with strong inducers of CYP3A is not recommended.

Store LITFULO at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep in original package.