Cibinqo Tablet, Film Coated
FDA Label NDC 63539-236

Serious Infections

Patients treated with CIBINQO may be at increased risk for developing serious infections that may lead to hospitalization or death; The most frequent serious infections reported with CIBINQO were herpes simplex, herpes zoster, and pneumonia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

If a serious or opportunistic infection develops, discontinue CIBINQO and control the infection.

Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

Avoid use of CIBINQO in patients with an active, serious infection including localized infections. The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1)].

Mortality

In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another JAK inhibitor to TNF blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. CIBINQO is not approved for use in RA patients [see Warnings and Precautions (5.2)].

Malignancies

Malignancies were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions (5.3)].

Major Adverse Cardiovascular Events

Major adverse cardiovascular events were reported in patients treated with CIBINQO. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4)].

Thrombosis

Deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with CIBINQO. Thrombosis, including PE, DVT, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid CIBINQO in patients at risk. If symptoms of thrombosis occur, discontinue CIBINQO and treat appropriately [see Warnings and Precautions (5.5)].

Renal Impairment

CIBINQO dosage recommendations for patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. In subjects with mild and moderate renal impairment, if an adequate response is not achieved after 12 weeks, dose of CIBINQO can be doubled [see Dosage and Administration (2.2)].

Table 1. Dosage Recommendations in Patients with Renal Impairment

Renal Impairment Stage	Estimated Glomerular Filtration (eGFR) Glomerular filtration rate was estimated by the Modification of Diet in Renal Disease (MDRD) formula.	Dosage
Mild	60 – 89 mL/minute	CIBINQO 100 mg once daily
Moderate	30 – 59 mL/minute	CIBINQO 50 mg once daily
Severe Severe Renal Impairment and End-Stage Renal Disease include patients on renal replacement therapy.	15 – 29 mL/minute	Not recommended for use
End-Stage Renal Disease (ESRD)	<15 mL/minute

Hepatic Impairment

CIBINQO is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Serious or Opportunistic Infections

If a patient develops a serious or opportunistic infection, discontinue CIBINQO and control the infection. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO [see Warnings and Precautions (5.1)].

Hematologic Abnormalities

Recommendations for CIBINQO discontinuation for laboratory abnormalities are summarized in Table 2.

Table 2. Recommendations for CIBINQO Discontinuation for Hematologic Abnormalities

Laboratory Measure	Recommendation
Abbreviations: ALC=absolute lymphocyte count; ANC=absolute neutrophil count; CBC=complete blood count; Hb=hemoglobin
Platelet Count <50,000/mm3	Discontinue CIBINQO and follow with CBC until >100,000/mm3
ALC <500/mm3	Treatment should be temporarily discontinued if ALC is less than 500 cells/mm3 and may be restarted once ALC return above this value
ANC <1,000/mm3	Treatment should be temporarily discontinued if ANC is less than 1,000 cells/mm3 and may be restarted once ANC return above this value
Hb value <8 g/dL	Treatment should be temporarily discontinued if Hb is less than 8 g/dL and may be restarted once Hb return above this value

CBC evaluations are recommended at baseline, 4 weeks after treatment initiation and 4 weeks after dosing increase of CIBINQO. Laboratory evaluations may be extended for patients on chronic CIBINQO therapy who develop hematologic abnormalities [see Warnings and Precautions (5.6)].

Tuberculosis

Evaluate and test patients for TB before starting CIBINQO therapy and consider yearly screening for patients in highly endemic areas for TB. CIBINQO is not recommended for use in patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, or for patients with a negative test for latent TB but who are at high risk for TB infection, start preventive therapy for latent TB prior to initiation of CIBINQO. Monitor patients for the development of signs and symptoms of TB, including patients who were tested negative for latent TB infection prior to initiating therapy.

Viral Reactivation

Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies with CIBINQO [see Adverse Reactions (6.1)]. If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves.

Hepatitis B virus (HBV) reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C [see Clinical Pharmacology (12.3)]. Monitor patients with inactive HBV for expression of HBV DNA during therapy with CIBINQO. If HBV DNA is detected during therapy with CIBINQO, consult a liver specialist.

Hematologic Abnormalities

Treatment with CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia [see Adverse Reactions (6.1)]. Prior to CIBINQO initiation, perform a CBC [see Dosage and Administration (2.1)]. CBC evaluations are recommended at 4 weeks after initiation and 4 weeks after dose increase of CIBINQO. Discontinuation of CIBINQO therapy is required for certain laboratory abnormalities [see Dosage and Administration (2.6)].

Lipid Elevations

Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO [see Adverse Reactions (6.1)]. Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy and thereafter patients should be managed according to clinical guidelines for hyperlipidemia. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

Specific Adverse Reactions

Exposure adjusted incidence rates were adjusted by trial size for all the adverse reactions reported in this section.

Overall Infections

In the placebo-controlled trials, for up to 16 weeks, overall infections were reported in 90 subjects (126.8 per 100 patient-years) treated with placebo, 211 subjects (168.8 per 100 patient-years) treated with CIBINQO 100 mg and 204 subjects (159.5 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, overall infections were reported in 427 subjects (91.8 per 100 patient-years) treated with CIBINQO 100 mg and 394 subjects (103.2 per 100 patient-years) treated with CIBINQO 200 mg.

Serious Infections

In the placebo-controlled trials, for up to 16 weeks, serious infections were reported in 2 subjects (2.6 per 100 patient-years) treated with placebo, 6 subjects (3.9 per 100 patient-years) treated with CIBINQO 100 mg, and 2 subjects (1.3 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, serious infections were reported in 18 subjects (2.3 per 100 patient-years) treated with CIBINQO 100 mg and 16 subjects (2.3 per 100 patient-years) treated with CIBINQO 200 mg. The most commonly reported serious infections were herpes simplex, herpes zoster, and pneumonia.

Herpes Zoster

In the placebo-controlled trials, for up to 16 weeks, opportunistic infections were generally cases of multidermatomal cutaneous herpes zoster. Herpes zoster was reported in 0 subjects treated with placebo, 3 subjects (1.9 per 100 patient-years) treated with CIBINQO 100 mg and 8 subjects (5.1 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, herpes zoster was reported in 16 subjects (2.0 per 100 patient-years) treated with CIBINQO 100 mg and 35 subjects (5.2 per 100 patient-years) treated with CIBINQO 200 mg.

Malignancy

In the placebo-controlled trials, for up to 16 weeks, no malignancy was reported in subjects treated with placebo or CIBINQO 100 mg and in 1 patient (0.65 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, malignancy was reported in 4 subjects (0.5 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg.

Thrombosis

In all clinical trials, including the long-term extension trial, pulmonary embolism was reported in 3 subjects (0.4 per 100 patient-years), who were treated with CIBINQO 200 mg. Deep vein thrombosis was reported in 2 subjects (0.3 per 100 patient-years) who were treated with CIBINQO 200 mg. No thrombosis occurred in subjects treated with CIBINQO 100 mg.

Major Adverse Cardiovascular Events

In the placebo-controlled trials, for up to 16 weeks, major adverse cardiovascular event (MACE) was reported in 1 subject (0.6 per 100 patient-years) treated with CIBINQO 100 mg. In all 5 clinical trials, including the long-term extension trial, MACE was reported in 1 patient (0.1 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg.

Thrombocytopenia

In the placebo-controlled trials, for up to 16 weeks, treatment with CIBINQO was associated with a dose-related decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which the platelet count returned towards baseline despite continued therapy. In all 5 clinical trials, including the long-term extension trial 6 subjects (0.9 per 100 patient-years) treated with CIBINQO 200 mg had adverse reactions of thrombocytopenia, no subjects treated with CIBINQO 100 mg had an adverse reaction of thrombocytopenia.

Lymphopenia

In the placebo-controlled trials, for up to 16 weeks, confirmed ALC <500/mm³ occurred in 2 subjects (1.2 per 100 patient-years) treated with CIBINQO 200 mg and 0 subjects treated with CIBINQO 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure.

Lipid Elevations

In the placebo-controlled trials, for up to 16 weeks, there was a dose-related percent increase in low-density lipoprotein cholesterol (LDL-c), total cholesterol, and high-density lipoprotein cholesterol (HDL-c) relative to placebo at Week 4 which remained elevated through the final visit in the treatment period. Adverse reactions related to hyperlipidemia occurred in 1 subject (0.6 per 100 patient-years) exposed to CIBINQO 100 mg, 3 subjects (2.0 per 100 patient-years) exposed to CIBINQO 200 mg.

Retinal Detachment

In the placebo-controlled trials, for up to 16 weeks, retinal detachment occurred in 1 subject (0.6 per 100 patient-years) treated with CIBINQO 100 mg. In all 5 clinical trials, including the long-term extension trial, retinal detachment occurred in 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 100 mg.

Creatine Phosphokinase Elevations (CPK)

In the placebo-controlled trials, for up to 16 weeks, events of blood CPK increased were reported in 6 subjects (7.5 per 100 patient-years) treated with placebo, 11 subjects (6.9 per 100 patient-years) treated with 100 mg of CIBINQO and 19 subjects (12.3 per 100 patient-years) treated with 200 mg of CIBINQO. Most elevations were transient, there were no reported adverse reactions of rhabdomyolysis.

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIBINQO during pregnancy. Pregnant women exposed to CIBINQO and health care providers are encouraged to call 1-877-311-3770.

Risk Summary

Available data from pregnancies reported in clinical trials with CIBINQO are not sufficient to establish a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of abrocitinib to pregnant rats and rabbits during organogenesis at exposure 14 or 5 times the maximum recommended human dose (MRHD) based on AUC comparison, respectively, resulted in maternal dystocia and skeletal variations in rats and no adverse effects in rabbits (see Data).

The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risks in the U.S. general population of major birth defects and miscarriages are 2–4% and 15–20% of clinically recognized pregnancies, respectively.

Data

Animal Data

In an embryofetal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, or 60 mg/kg/day during the period of organogenesis. No fetal malformations were observed. Abrocitinib increased the incidence of skeletal variations of short 13^th ribs at 30 mg/kg/day (14 times the MRHD based on AUC comparison). Increased embryofetal lethality and additional skeletal variations (cervical arches with reduced ventral processes, thickened ribs, and unossified metatarsals) were noted at 60 mg/kg/day (22 times the MRHD based on AUC comparison).

In an embryofetal development study, abrocitinib was administered orally to pregnant rabbits at doses of 10, 30, or 75 mg/kg/day during the period of organogenesis. No abrocitinib-related maternal or developmental toxicity was noted at doses up to 75 mg/kg/day (5 times the MRHD based on AUC comparison).

In a prenatal and postnatal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, and 60 mg/kg/day beginning on gestation day 6 and continuing through lactation day 20. Dystocia with prolonged parturition and reduced offspring body weights were noted at 30 mg/kg/day (14 times the MRHD based on AUC comparison). Postnatal survival was markedly decreased at 60 mg/kg/day (22 times the MRHD based on AUC comparison). No maternal toxicity was observed at 10 mg/kg/day (3 times the MRHD based on AUC comparison). No abrocitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring was noted at doses up to 30 mg/kg/day (14 times the MRHD based on AUC comparison).

Risk Summary

There are no data on the presence of abrocitinib in human milk, the effects on the breast-fed infant, or the effects on milk production. Abrocitinib was secreted in milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, malignancy, and thrombosis, advise women not to breastfeed during treatment with CIBINQO and for one day after the last dose (approximately 5–6 elimination half-lives).

Data

Animal Data

Lactating female rats were orally administered a single dose of 10 mg/kg abrocitinib on lactation day 12. Abrocitinib AUC was approximately 5 times greater in milk than in plasma.

Infertility

Females

Based on the findings in rats, oral administration of CIBINQO may impair female fertility. Impaired fertility in female rats was reversible 1 month after cessation of abrocitinib oral administration [see Nonclinical Toxicology (13.1)].

Juvenile Animal Toxicity Data

In a juvenile animal toxicity study, abrocitinib was administered orally to juvenile rats at doses of 5, 25, and 75 mg/kg/day beginning on postnatal day 10 (approximately equivalent to a human infant) and continuing through postnatal day 63 (approximately equivalent to an adolescent). Abrocitinib caused a reversible, dose-related decrease in the primary spongiosa in the metaphysis of the proximal tibia and distal femur. Abrocitinib produced adverse effects on bone development at all dose levels. Abrocitinib caused irreversible dose-related small or misshapen femoral heads at doses ≥5 mg/kg/day (1.1 times the MRHD based on AUC comparison). Abrocitinib also irreversibly decreased femur size and caused paw malrotation and limb impairment at doses ≥25 mg/kg/day (10 times the MRHD based on AUC comparison). At 75 mg/kg/day (36 times the MRHD based on AUC comparison), paw fractures generally corresponded to limb impairment, a fractured tibia was noted in a single female, and effects noted at lower doses were increased in frequency and severity. Irreversible bone findings have not been observed in older animals.

Effect on Platelet Count

Treatment with CIBINQO was also associated with a transient, dose-dependent decrease in platelet count with the nadir occurring at a median of 24 days after continuous administration of abrocitinib 200 mg once daily. The percent change from baseline of the nadir increases with decreasing baseline platelet counts (-41.2%, -33.4%, and -26.5% for baseline platelet counts of 170, 220, and 270× 10³/mm³, respectively). Recovery of platelet count (~40% recovery by 12 weeks) occurred without discontinuation of the treatment.

Cardiac Electrophysiology

At a dose 3 times the maximum approved recommended dose, abrocitinib does not prolong the QT interval to any clinically relevant extent.

Absorption

Abrocitinib is absorbed with over 91% extent of oral absorption and absolute oral bioavailability of approximately 60%. The peak plasma concentrations of abrocitinib are reached within 1 hour.

Effect of Food

Coadministration of CIBINQO with a high-fat, high-calorie meal (total 916 calories, with approximate distribution of 55% fat, 29% carbohydrates, and 16% protein) had no clinically relevant effect on abrocitinib exposures (AUC and C_max of abrocitinib increased by approximately 26% and 29%, respectively, and T_max was prolonged by 2 hours) [see Dosage and Administration (2.7)].

Distribution

After intravenous administration, the volume of distribution of abrocitinib is approximately 100 L. Approximately 64%, 37% and 29% of circulating abrocitinib and its active metabolites M1 and M2, respectively, are bound to plasma proteins. Abrocitinib and its active metabolites M1 and M2 bind predominantly to albumin and distribute equally between red blood cells and plasma.

Elimination

Abrocitinib is eliminated primarily by metabolic clearance mechanisms. The mean elimination half-lives of abrocitinib and its two active metabolites, M1 and M2, range 3 to 5 hours.

Metabolism

The metabolism of abrocitinib is mediated by multiple CYP enzymes, CYP2C19 (~53%), CYP2C9 (~30%), CYP3A4 (~11%) and CYP2B6 (~6%). In a human radiolabeled study, abrocitinib was the most prevalent circulating species, with two active polar mono-hydroxylated metabolites identified as M1 (3-hydroxypropyl), and M2 (2-hydroxypropyl). Metabolite M1 is less active than abrocitinib while metabolite M2 is as active as the parent. The pharmacologic activity of abrocitinib is attributable to the unbound exposure of parent molecule (~60%) as well as M1 (~10%) and M2 (~30%) in systemic circulation. The sum of unbound exposures of abrocitinib, M1 and M2, each expressed in molar units and adjusted for relative potencies, is referred to as the combined exposure of abrocitinib and its two active metabolites, M1 and M2.

Excretion

After a single radiolabeled abrocitinib dose, less than 1% of the dose was excreted in urine as unchanged drug. The metabolites of abrocitinib, M1 and M2 are excreted predominantly in urine, and are substrates of OAT3 transporter.

Specific Populations

Body weight, sex, race, and age did not have a clinically meaningful effect on CIBINQO exposure.

Patients with Renal Impairment

In a renal impairment study, subjects with severe (eGFR <30 mL/min as estimated by MDRD equation) and moderate (eGFR 30–59 mL/min, MDRD) renal impairment had approximately 191% and 110% increase in the combined exposure (AUC_inf,u) of abrocitinib and its active metabolites, M1 and M2, respectively, compared to subjects with normal renal function (eGFR ≥90 mL/min, MDRD). Based on these results, a clinically significant increase in the combined exposure of abrocitinib and its active metabolites, M1 and M2, is not expected in subjects with mild renal impairment (eGFR 60 –89 mL/min, MDRD) [see Dosage and Administration (2.3) and Use in Specific Population (8.6)].

CIBINQO has not been studied in subjects on renal replacement therapy [see Dosage and Administration (2.3) and Use in Specific Population (8.6)]. In Phase 3 clinical studies, CIBINQO was not evaluated in subjects with atopic dermatitis with baseline creatinine clearance values less than 40 mL/min.

Patients with Hepatic Impairment

Subjects with mild hepatic impairment (Child Pugh A) had approximately 4% decrease in the combined exposure (AUC_inf,u) of abrocitinib and its two active metabolites, M1 and M2, compared to subjects with normal hepatic function. Subjects with moderate hepatic impairment (Child Pugh B) had approximately 15% increase in the combined exposure (AUC_inf,u) of abrocitinib and its two active metabolites, M1 and M2, compared to subjects with normal hepatic function. These changes are not clinically significant. In clinical studies, CIBINQO has not been studied in subjects with severe (Child Pugh C) hepatic impairment, or in subjects screened positive for active hepatitis B or hepatitis C [see Use in Specific Populations (8.7) and Warnings and Precautions (5.1)].

Drug Interaction Studies

Clinical Studies

The effect of coadministered drugs on the pharmacokinetics of abrocitinib is presented in Table 6.

Table 6. Change in Pharmacokinetics of the Combined Exposure of Abrocitinib and its Two Active Metabolites (M1 and M2) in the Presence of Coadministered Drugs

Coadministered Drugs	Regimen of Coadministered Drug	Dose of Abrocitinib	Ratio Ratios for Cmax,u and AUCinf,u compare coadministration of the drug with abrocitinib versus administration of abrocitinib alone. (90% Confidence Interval)
			Cmax,u	AUCinf,u
Strong CYP2C19 and moderate CYP3A inhibitor: Fluvoxamine [see Drug Interactions (7.1)]	50 mg once daily × 9 days	100 mg	1.33 (1.00–1.78)	1.91 (1.74–2.10)
Strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor: Fluconazole [see Drug Interactions (7.1)]	400 mg on Day 1 and 200 mg on Days 2–7	100 mg	1.23 (1.08–1.42)	2.55 When coadministered with Fluconazole, the systemic exposure of abrocitinib was approximately 4.8-fold higher compared to when abrocitinib is administered alone. (2.42–2.69)
Strong CYP Enzymes Inducers: Rifampin [see Drug Interactions (7.1)]	600 mg once daily × 8 days	200 mg	0.69 (0.50–0.94)	0.44 (0.41–0.47)
OAT3 inhibitor: Probenecid Drug interaction with OAT3 inhibitor is not clinically significant.	1,000 mg twice daily × 3 days	200 mg	1.30 (1.04–1.63)	1.66 (1.52–1.80)

The effect of abrocitinib on the pharmacokinetics of coadministered drugs is presented in Table 7.

Table 7. Change in Pharmacokinetics of Coadministered Drugs in the Presence of Abrocitinib

Coadministered Drugs or In Vivo Markers of CYP Activity	Dose Regimen of Abrocitinib	Ratio Ratios for Cmax and AUCinf compare coadministration of abrocitinib with the drug versus administration of the drug alone. (90% Confidence Interval)
		Cmax	AUCinf
Oral contraceptive: Ethinyl estradiol (EE) and levonorgestrel (LN)	200 mg once daily × 9 days	EE: 1.07 (0.99, 1.15) LN: 0.86 (0.75, 0.97)	EE: 1.19 (1.12, 1.26) LN AUClast of levonorgestrel was reported in lieu of AUCinf because the terminal phase of levonorgestrel was not well characterized. : 0.98 (0.87, 1.10)
Sensitive CYP3A Substrate: Midazolam	200 mg once daily × 7 days	0.93 (0.84, 1.04)	0.92 (0.86, 0.99)
Sensitive P-gp substrate: Dabigatran	200 mg single dose	1.40 (0.92, 2.13)	1.53 (1.09, 2.15)
Sensitive BCRP and OAT3 substrate: Rosuvastatin	200 mg once daily × 3 days	0.99 (0.86, 1.14)	1.02 (0.93, 1.12)
Sensitive MATE1/2K substrate: Metformin	200 mg once daily × 2 days	0.88 (0.81, 0.96)	0.93 (0.85, 1.03)

Coadministration of dabigatran etexilate (a P-gp substrate), with a single dose of CIBINQO 200 mg increased dabigatran AUC_inf and C_max by approximately 53% and 40%, respectively, compared with administration alone. These increases in dabigatran exposure are not considered clinically significant change. However, appropriate dose titration of P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities (e.g., digoxin) when coadministered with the CIBINQO would be needed.

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Abrocitinib and its metabolites M1 and M2 are not inhibitors or inducers of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.

Uridine diphosphate (UDP)-glucuronosyl transferase (UGT) Enzymes: Abrocitinib and its metabolites M1 and M2 are not inhibitors or inducers of UGT1A1, UGT1A4, UGT1A6, UGT1A9, or UGT2B7.

Transporter Systems: Abrocitinib is an inhibitor of organic cation transporter (OCT)1 but is not an inhibitor of organic anion transporting polypeptide (OATP)1B1/1B3, bile salt export pump (BSEP), OAT1 or OCT2.

Clinical Response

Monotherapy Trials

The results of the CIBINQO monotherapy trials (Trial-AD-1 and Trial-AD-2) are presented in Table 9.

Table 9. Efficacy Results of CIBINQO Monotherapy at Week 12 in Subjects with Moderate-to-Severe AD (Trial-AD-1 and Trial-AD-2)

	Trial-AD-1			Trial-AD-2
	CIBINQO		Placebo N=77	CIBINQO		Placebo N=78
	200 mg QD N=154	100 mg QD N=156		200 mg QD N=155	100 mg QD N=158
Abbreviations: CI=confidence interval; EASI=Eczema Area and Severity Index; IGA=Investigator Global Assessment; QD=once daily.
IGA 0 or 1 IGA responders were subjects with IGA score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥2 points.	44%	24%	8%	38%	28%	9%
Difference from Placebo (95% CI)	36% (26%, 46%)	16% (7%, 25%)	-	29% (19%, 39%)	19% (9%, 29%)	-
EASI-75 EASI -75 responders were patients with ≥75% improvement in EASI from baseline.	62%	40%	12%	61%	44%	10%
Difference from Placebo (95% CI)	51% (40%, 61%)	28% (18%, 39%)	-	50% (40%, 61%)	33% (23%, 44%)	-

The proportion of subjects achieving PP-NRS4 at Week 2 (defined as an improvement of ≥4 points from baseline in PP-NRS) was higher in subjects treated with CIBINQO monotherapy 200 mg once daily (28% in Trial-AD-1 and 24% in Trial-AD-2) and 100 mg once daily (11% in both trials) compared to placebo (2% in both trials).

A higher proportion of subjects in the CIBINQO monotherapy 100 mg or 200 mg once daily arm compared to placebo achieved improvement in itching at Week 12.

Combination Therapy Trial

The results of CIBINQO in combination with background topical corticosteroids (Trial-AD-3) are presented in Table 10.

Table 10. Efficacy Results of CIBINQO with Concomitant Topical Corticosteroids at Week 12 in Subjects with Moderate-to-Severe AD (Trial-AD-3)

% Responders	CIBINQO		Placebo N=131
	200 mg QD N=226	100 mg QD N=238
Abbreviations: CI=confidence interval; EASI=Eczema Area and Severity Index; IGA=Investigator Global Assessment; QD=once daily.
IGA 0 or 1 IGA responders were subjects with IGA score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥2 points. at Week 12	47%	36%	14%
Difference from Placebo (95% CI)	34% (25%, 42%)	23% (15%, 31%)	-
EASI-75 EASI-75 responders were subjects with ≥75% improvement in EASI, from baseline. at Week 12	68%	58%	27%
Difference from Placebo (95% CI)	41% (32%, 51%)	32% (22%, 41%)	-

The proportions of subjects achieving PP-NRS4 at Week 2 was higher in subjects treated with CIBINQO 200 mg once daily (30%) and 100 mg once daily (14%) in combination with background medicated topical therapies compared to placebo (8%).

Examination of age, gender, race, weight and previous systemic AD therapy treatment did not identify differences in response to CIBINQO 100 mg or 200 mg once daily among these subgroups in Trial-AD-1, Trial-AD-2, and Trial-AD-3.

Pregnancy Registry

Advise patients to report their pregnancy to 1-877-311-3770 [see Use in Specific Populations (8.1)].

Serious Infections

Inform patients that they may develop infections when taking CIBINQO. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection [see Warnings and Precautions (5.1)].

Advise patients that the risk of herpes zoster is increased in patients treated with CIBINQO and some cases can be serious [see Warnings and Precautions (5.1)].

Malignancies

Inform patients that CIBINQO may increase their risk of certain cancers, including skin cancers. Periodic skin examinations are recommended while using CIBINQO. Advise patients that exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see Warnings and Precautions (5.3)].

Major Adverse Cardiovascular Events

Inform patients that CIBINQO may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)].

Thrombosis

Advise patients that events of DVT and PE have been reported in clinical trials with CIBINQO. Instruct patients to seek immediate medical attention if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)].

Laboratory Abnormalities

Inform patients that CIBINQO may affect certain lab tests, and that blood tests are required before and during CIBINQO treatment [see Dosage and Administration (2.1) and Warnings and Precautions (5.6)].

Immunizations

Advise patients that vaccination with live vaccines is not recommended during CIBINQO treatment and immediately prior to or after CIBINQO treatment. Instruct patients to inform the healthcare practitioner that they are taking CIBINQO prior to a potential vaccination [see Warnings and Precautions (5.7)].

Retinal Detachment

Inform patients that retinal detachment has been reported in clinical trials for atopic dermatitis in patients who received CIBINQO. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving CIBINQO [see Adverse Reactions (6.1)].

Infertility

Advise females of reproductive potential that CIBINQO may impair fertility [see Use in Specific Populations (8.3)].

Lactation

Advise a woman not to breastfeed during treatment with CIBINQO [see Use in Specific Populations (8.2)].

Administration

Advise patients not to chew, crush, or split CIBINQO tablets [see Dosage and Administration (2.7)].

This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

For Medical Information about CIBINQO, please visit www.pfizermedinfo.com or call 1-800-438-1985.



Logo (Cibinqo 02)

LAB-1423-1.0

CIBINQO is indicated for the treatment of adults with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Perform the following tests and evaluations prior to CIBINQO initiation:

• Tuberculosis (TB) infection evaluation – CIBINQO 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 CIBINQO [see Warnings and Precautions (5.1)].
• Viral hepatitis screening in accordance with clinical guidelines – CIBINQO initiation is not recommended in patients with active hepatitis B or hepatitis C [see Warnings and Precautions (5.1)].
• A complete blood count (CBC) – CIBINQO initiation is not recommended in patients with a platelet count <150,000/mm³, an absolute lymphocyte count <500/mm³, an absolute neutrophil count <1,000/mm³, or a hemoglobin value <8 g/dL [see Warnings and Precautions (5.6)].

Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines prior to CIBINQO initiation [see Warnings and Precautions (5.7)].

The recommended dosage of CIBINQO is 100 mg orally once daily.

If an adequate response is not achieved with CIBINQO 100 mg orally daily after 12 weeks, consider increasing dosage to 200 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 200 mg once daily.

CIBINQO can be used with or without topical corticosteroids.

If a dose is missed, administer the dose as soon as possible unless it is less than 12 hours before the next dose, in which case skip the missed dose. Thereafter, resume dosing at the regular scheduled time.

In patients who are known or suspected to be CYP2C19 poor metabolizers, the recommended dosage of CIBINQO is 50 mg once daily [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.5)]. If an adequate response is not achieved with CIBINQO 50 mg orally daily after 12 weeks, consider increasing dosage to 100 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily.

In patients taking strong inhibitors of cytochrome P450 (CYP) 2C19 reduce the dosage to 50 mg once daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. If an adequate response is not achieved with CIBINQO 50 mg orally daily after 12 weeks, consider increasing dosage to 100 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily.

Administer CIBINQO with or without food at approximately the same time each day.

Swallow CIBINQO tablets whole with water. Do not crush, split, or chew CIBINQO tablets.

• 50 mg: Pink, oval, film-coated tablet debossed with "PFE" on one side and "ABR 50" on the other.
• 100 mg: Pink, round, film-coated tablet debossed with "PFE" on one side and "ABR 100" on the other.
• 200 mg: Pink, oval, film-coated tablet debossed with "PFE" on one side and "ABR 200" on the other.

CIBINQO is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment [see Warnings and Precautions (5.6), Drug Interactions (7.2), and Clinical Pharmacology (12.2)].

The most frequent serious infections reported in clinical studies with CIBINQO for atopic dermatitis were herpes simplex, herpes zoster, and pneumonia [see Adverse Reactions (6.1)]. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions.

Avoid use of CIBINQO in patients with active, serious infection including localized infections.

Consider the risks and benefits of treatment prior to initiating CIBINQO in patients:

• with chronic or recurrent infection
• who have been exposed to tuberculosis
• with a history of a serious or an opportunistic infection
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
• with underlying conditions that may predispose them to infection

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with CIBINQO. If a patient develops a serious or opportunistic infection, discontinue CIBINQO. Initiate complete diagnostic testing and appropriate antimicrobial therapy. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO.

In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. CIBINQO is not approved for use in RA.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO.

Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical studies with CIBINQO for atopic dermatitis [see Adverse Reactions (6.1)].

Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.

Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

Major adverse cardiovascular events were reported in clinical studies of CIBINQO for atopic dermatitis [see Adverse Reactions (6.1)].

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in patients receiving CIBINQO in the clinical studies for atopic dermatitis [see Adverse Reactions (6.1)].

Thrombosis, including DVT, PE, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death.

In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. CIBINQO is not approved for use in RA.

Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and evaluate and treat patients appropriately.

Prior to initiating CIBINQO, complete all age-appropriate vaccinations as recommended by current immunization guidelines including prophylactic herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during, and immediately after CIBINQO therapy.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Serious Infections [see Warnings and Precautions (5.1)]
• Mortality [see Warnings and Precautions (5.2)]
• Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3)]
• Major Adverse Cardiovascular Events [see Warnings and Precautions (5.4)]
• Thrombosis [see Warnings and Precautions (5.5)]
• Laboratory Abnormalities [see Warnings and Precautions (5.6)]

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 CIBINQO was evaluated in four randomized, placebo-controlled clinical trials (2 monotherapy, 1 combination therapy with topical corticosteroid, and 1 dose-ranging) and one long-term extension trial in subjects with moderate to severe atopic dermatitis (AD). A total of 1623 subjects with moderate to severe atopic dermatitis were treated with CIBINQO in these clinical trials representing 1428 patient-years of exposure. There were 634 subjects with at least 1 year of exposure to CIBINQO.

In the placebo-controlled clinical trials, a total of 1198 subjects were exposed to CIBINQO with 608 subjects receiving CIBINQO 100 mg once daily and 590 subjects receiving CIBINQO 200 mg once daily for up to 16 weeks. The median age of subjects was 33.0 years, 124 subjects (8.1%) were 12 to less than 18 years old and 94 subjects (6.1%) were 65 years of age or older. The majority of subjects were White (68.7%) and male (53.9%). While subjects aged 12 to 17 years were included in these trials, CIBINQO is not approved for use in pediatric subjects [see Use in Specific Populations (8.4)].

Adverse reactions occurring at ≥1% in any of the treated groups and at a higher rate than in the placebo group are presented in Table 3. A total of 61 (5.1%) subjects treated with CIBINQO were discontinued from the trials due to adverse reactions. The safety profile of CIBINQO in the monotherapy and the combination trial(s) were similar.

Table 4 includes drugs with clinically significant drug interactions affecting CIBINQO.

Table 5 includes clinically significant drug interactions affecting other drugs.

The safety and effectiveness of CIBINQO have not been established in pediatric patients.

A total of 145 (4.6%) patients 65 years of age and older, while 25 (0.8%) were 75 years of age and older, were enrolled in CIBINQO clinical trials. Clinical trials of CIBINQO did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

A higher proportion of patients 65 years of age and older discontinued from clinical trials compared to younger patients. Among all patients exposed to CIBINQO, including the long-term extension trial, confirmed ALC <500/mm³ occurred only in patients 65 years of age and older. A higher proportion of patients 65 years of age and older had platelet counts <75,000/mm³. The incidence rate of herpes zoster in patients 65 years of age and older treated with CIBINQO (7.40 per 100 patient-years) was higher than that of patients 18 to less than 65 years of age (3.44 per 100 patient-years).

In patients with severe (eGFR <30 mL/min) and moderate (eGFR 30–59 mL/min) renal impairment, the combined exposure (AUC_inf,u) of abrocitinib and its two active metabolites, M1 and M2, is increased compared to patients with normal renal function (eGFR ≥90 mL/min) [see Clinical Pharmacology (12.3)]. This may increase the risk of adverse reactions such as infections.

CIBINQO is not recommended for use in patients with severe renal impairment and ESRD including those on renal replacement [see Dosage and Administration (2.3)].

A dosage reduction in patient with moderate renal impairment is recommended. No dosage adjustment is required in patients with mild renal impairment (eGFR 60–89 mL/min) [see Dosage and Administration (2.3)].

CIBINQO has not been studied in patients on renal replacement therapy. In Phase 3 clinical trials, CIBINQO was not evaluated in patients with atopic dermatitis with baseline creatinine clearance values less than 40 mL/min.

Avoid use of CIBINQO in patients with severe (Child Pugh C) hepatic impairment.

Dosage adjustment is not required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment based on similar combined exposure (AUC_inf,u) of abrocitinib and its two active metabolites, M1 and M2 compared to patients with normal hepatic function. In clinical trials, CIBINQO was not evaluated in patients with severe (Child Pugh C) hepatic impairment [see Clinical Pharmacology (12.3)].

In patients who are CYP2C19 poor metabolizers, the AUC of abrocitinib is increased compared to CYP2C19 normal metabolizers due to reduced metabolic clearance. Dosage reduction of CIBINQO is recommended in patients who are known or suspected to be CYP2C19 poor metabolizers based on genotype or previous history/experience with other CYP2C19 substrates [see Dosage and Administration (2.4) and Clinical Pharmacology (12.5)].

There is no experience regarding human overdosage with CIBINQO. There is no specific antidote for overdose with CIBINQO. In case of an overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations.

CIBINQO (abrocitinib) tablets contain the free base of abrocitinib, a Janus kinase (JAK) inhibitor, for oral administration.

Abrocitinib is a white to pale colored powder with the following chemical name: N-((1s,3s)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide

The solubility of abrocitinib in water is 0.04 mg/mL at 25°C.

Abrocitinib has a molecular weight of 323.42 g/mol and a molecular formula of C₁₄H₂₁N₅O₂S. The structural formula of abrocitinib is:

Chemical Structure (Cibinqo 01)

Each film-coated tablet contains 50 mg or 100 mg or 200 mg of abrocitinib and the following inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose, iron oxide red, lactose monohydrate, Macrogol, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, titanium dioxide, and triacetin.

CIBINQO is a Janus kinase (JAK) inhibitor.

Abrocitinib reversibly inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site. In a cell-free isolated enzyme assay, abrocitinib was selective for JAK1 over JAK2 (28-fold), JAK3 (>340-fold), and tyrosine kinase (TYK) 2 (43-fold), as well as the broader kinome. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. Both the parent compound and the active metabolites inhibit JAK1 activity in vitro with similar levels of selectivity.

Treatment with CIBINQO was associated with dose-dependent reduction in serum markers of inflammation, including high sensitivity C-reactive protein (hsCRP), interleukin-31 (IL-31) and thymus and activation regulated chemokine (TARC). These changes returned to near baseline within 4 weeks of drug discontinuation.

Abrocitinib plasma C_max and AUC increased dose proportionally up to 200 mg. Steady-state plasma concentrations of abrocitinib are achieved within 48 hours after once daily administration.

Patients who are CYP2C19 poor metabolizers have little to no CYP2C19 enzyme function compared to CYP2C19 normal metabolizers that have fully functional CYP2C19 enzymes.

After single doses of abrocitinib, CYP2C19 poor metabolizers demonstrated dose-normalized AUC of abrocitinib values that were 2.3-fold higher when compared to CYP2C19 normal metabolizers. Approximately 3–5% of Caucasians and Blacks and 15 to 20% of Asians are CYP2C19 poor metabolizers [see Dosage and Administration (2.4) and Use in Specific Populations (8.8)].

In a 2-year oral carcinogenicity study in rats, abrocitinib increased the incidence of benign thymomas in female rats at doses of 10 and 30 mg/kg/day (4 and 19 times the MRHD, respectively, based on AUC comparison). Abrocitinib was not carcinogenic in female rats at 3 mg/kg/day (0.8 times the MRHD based on AUC comparison) or male rats at doses up to 30 mg/kg/day (19 times the MRHD based on AUC comparison). Abrocitinib was not carcinogenic in Tg.rasH2 mice at oral doses up to 60 mg/kg/day in males and 75 mg/kg/day in females.

Abrocitinib was not mutagenic in the bacterial mutagenicity assay (Ames assay). Although abrocitinib was aneugenic in the in vitro TK6 micronucleus assay, abrocitinib was not aneugenic or clastogenic in an in vivo rat bone marrow micronucleus assay.

Abrocitinib did not impair male fertility at doses up to 70 mg/kg/day (35 times the MRHD based on AUC comparison) or female fertility at 10 mg/kg/day (3 times the MRHD based on AUC comparison). Abrocitinib impaired female fertility (reducing fertility index, corpora lutea, and implantation sites) at 70 mg/kg/day (39 times the MRHD based on AUC comparison). Impaired fertility in female rats reversed 1 month after cessation of abrocitinib administration.

The efficacy of CIBINQO as monotherapy and in combination with background topical corticosteroids were evaluated in 3 randomized, double-blind, placebo-controlled trials [Trial-AD-1 (NCT03349060), Trial-AD-2 (NCT03575871), and Trial-AD-3 (NCT03720470)] in 1615 subjects 12 years of age and older (CIBINQO is not approved for use in pediatric patients) with moderate-to-severe atopic dermatitis as defined by Investigator's Global Assessment (IGA) score ≥3, Eczema Area and Severity Index (EASI) score ≥16, body surface area (BSA) involvement ≥10%, and Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 at the baseline visit prior to randomization.

Overall, 53% of subjects were male, 69% of subjects were white, 64% of subjects had a baseline IGA score of 3 (moderate AD), and 36% of subjects had a baseline IGA score of 4 (severe AD). The baseline mean EASI score was 30. The baseline mean age was 36 years old with 8% of subjects 12 to less than 18 years old and 92% of subjects 18 years of age or older. Subjects in these trials were those who had inadequate response to previous topical therapy, or were subjects for whom topical treatments were medically inadvisable, or who had received systemic therapies including dupilumab. In each of the trials, over 40% of subjects had prior exposure to systemic therapy. In Trial-AD-1 and Trial-AD-2, 6% of the subjects had received dupilumab, whereas prior use of dupilumab was not allowed in Trial-AD-3.

Trial-AD-1, Trial-AD-2, and Trial-AD-3 assessed the co-primary endpoints of IGA and EASI-75 responses at Week 12. The designs of the trials are summarized in Table 8.

CIBINQO is supplied as:

Store CIBINQO at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in original package. The container closure system is child resistant.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

PROFESSIONAL SAMPLE-NOT FOR SALE
ALWAYS DISPENSE WITH
MEDICATION GUIDE

Pfizer
NDC 63539-236-14

CIBINQO_™
(abrocitinib) tablets

50 mg

Do not crush, split, or chew the tablets.

14 Tablets
Rx only

Principal Display Panel (50 mg Tablet Bottle Label)

PROFESSIONAL SAMPLE-NOT FOR SALE
ALWAYS DISPENSE WITH
MEDICATION GUIDE

Pfizer
NDC 63539-336-14

CIBINQO_™
(abrocitinib) tablets

100 mg

Do not crush, split, or chew the tablets.

14 Tablets
Rx only

Principal Display Panel (100 mg Tablet Bottle Label)

PROFESSIONAL SAMPLE-NOT FOR SALE
ALWAYS DISPENSE WITH
MEDICATION GUIDE

Pfizer
NDC 63539-436-14

CIBINQO_™
(abrocitinib) tablets

200 mg

Do not crush, split, or chew the tablets.

14 Tablets
Rx only

Principal Display Panel (200 mg Tablet Bottle Label)