TRIALISTMD · Drug Intelligence Platform
FDA APPROVED 2022
JAK1 Inhibitor · Dermatology · Atopic Dermatitis
Abrocitinib
CIBINQO® · Pfizer Labs, Division of Pfizer Inc.
A selective, reversible JAK1 inhibitor that blocks ATP binding at JAK1 with 28-fold selectivity over JAK2 and greater than 340-fold over JAK3 — the first oral once-daily JAK inhibitor approved for refractory moderate-to-severe atopic dermatitis in adults who have failed or cannot use other systemic therapies including biologics. Abrocitinib carries a Boxed Warning for serious infections, mortality, malignancy, MACE, and thrombosis consistent with the JAK inhibitor class.
Drug Overview
NDA 213871
⚠BOXED WARNING: Serious Infections · Mortality · Malignancy · Major Adverse Cardiovascular Events (MACE) · Thrombosis. See full prescribing information. Abrocitinib is not approved for RA patients. Higher rates of mortality, MACE, malignancy, and thrombosis observed with another JAK inhibitor vs TNF blockers in RA.
Indication
Refractory Moderate-to-Severe AD
Adults not adequately controlled with other systemic therapies including biologics, or when use is inadvisable
Mechanism
JAK1 Inhibitor
Selective, reversible JAK1 inhibitor; 28-fold selectivity over JAK2, >340-fold over JAK3
Starting Dose
100 mg QD
Increase to 200 mg QD if inadequate response at 12 weeks; DC if no response at 200 mg
Formulation
Oral Tablet
50 mg, 100 mg, 200 mg pink film-coated tablets; taken once daily with or without food
Mechanism of Action
Section 12.1Abrocitinib reversibly inhibits Janus kinase 1 (JAK1) by blocking the adenosine triphosphate (ATP) binding site. In a cell-free isolated enzyme assay, abrocitinib demonstrated selectivity for JAK1 over JAK2 (28-fold), JAK3 (>340-fold), and TYK2 (43-fold), as well as the broader kinome. Both the parent compound and its active metabolites (M1, M2) inhibit JAK1 activity in vitro with similar levels of selectivity. JAK1 is a key signaling node downstream of cytokines central to atopic dermatitis pathophysiology, including IL-4, IL-13, IL-31, and TSLP.
Pharmacodynamic effect: Treatment with abrocitinib produces dose-dependent reduction in serum markers of inflammation including hsCRP, IL-31 (pruritus mediator), and TARC (CCL17). These effects return to near baseline within 4 weeks of drug discontinuation, consistent with the short half-life of 3–5 hours.
Label note (Section 12.1): The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known per the prescribing information.
Competitive Landscape — Systemic Therapies for Moderate-to-Severe AD
| Drug | Target / Class | Route | Approval Status | Population |
|---|---|---|---|---|
| Abrocitinib (CIBINQO) | JAK1 inhibitor (oral) | Oral QD | FDA Jan 14, 2022 | Adults — refractory moderate-to-severe AD |
| Dupilumab (Dupixent) | IL-4Rα antagonist (biologic) | SC Q2W | FDA March 28, 2017 | Adults, adolescents, children ≥6 months |
| Tralokinumab (Adbry) | IL-13 antagonist (biologic) | SC Q2W | FDA Dec 27, 2021 | Adults — moderate-to-severe AD |
| Lebrikizumab (Ebglyss) | IL-13 antagonist (biologic) | SC Q2W/Q4W | FDA May 13, 2024 | Adults and adolescents ≥12 years |
| Upadacitinib (Rinvoq) | JAK1 inhibitor (oral) | Oral QD | FDA Jan 14, 2022 | Adults and adolescents ≥12 years — AD |
| Baricitinib (Olumiant) | JAK1/2 inhibitor (oral) | Oral QD | FDA May 13, 2022 | Adults — moderate-to-severe AD |
Source: FDA Prescribing Information NDA 213871, Ref ID 4920574, Revised 01/2022. Competitive landscape based on FDA approval records. Limitation of use: not recommended in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
Clinical Efficacy
Trial-AD-1 · Trial-AD-2 · Trial-AD-3 · Section 14Co-Primary Endpoints
IGA 0/1 & EASI-75
Assessed at Week 12 across all three pivotal trials
Trial Design
3 RCTs, DB, PC
2 monotherapy (12 wk) + 1 combination with TCS (16 wk); includes dupilumab arm in Trial-AD-3
Total Randomized (all trials)
1,615
AD-1: N=387 · AD-2: N=391 · AD-3: N=837 (subjects ≥12 years)
Eligibility Criteria
IGA ≥3, EASI ≥16
BSA ≥10%, PP-NRS ≥4; inadequate response to prior topical therapy
IGA 0/1 Response at Week 12 — Monotherapy
Trial-AD-1 (NCT03349060) & Trial-AD-2 (NCT03575871)TRIAL-AD-1 — IGA 0 or 1 (clear/almost clear) at Week 12 · N=387
Difference from placebo: 200 mg: 36% (95% CI: 26%–46%) · 100 mg: 16% (95% CI: 7%–25%)
TRIAL-AD-2 — IGA 0 or 1 (clear/almost clear) at Week 12 · N=391
Difference from placebo: 200 mg: 29% (95% CI: 19%–39%) · 100 mg: 19% (95% CI: 9%–29%)
EASI-75 Response at Week 12 — Monotherapy
TRIAL-AD-1 & TRIAL-AD-2 — EASI-75 (≥75% improvement from baseline) at Week 12
AD-1: 200 mg diff from placebo 51% (40%–61%) · 100 mg diff 28% (18%–39%)
AD-2: 200 mg diff from placebo 50% (40%–61%) · 100 mg diff 33% (23%–44%)
EASI-75 Over Time — Trial-AD-1 Monotherapy
Abrocitinib 200 mg QD
Abrocitinib 100 mg QD
Placebo
EASI-75 response rate (% subjects with ≥75% improvement from baseline EASI) over 12 weeks in Trial-AD-1 monotherapy. Week 12 values confirmed from label Table 9. Intermediate values estimated from published trial data. Source: FDA PI NDA 213871.
Combination Therapy Trial (Trial-AD-3) — Key Results
NCT03720470 · N=837 adults · 16 weeks with background TCS| Endpoint at Week 12 | Abrocitinib 200 mg + TCS (N=226) | Abrocitinib 100 mg + TCS (N=238) | Placebo + TCS (N=131) |
|---|---|---|---|
| IGA 0 or 1 | 47% Diff: +34% | 36% Diff: +23% | 14% |
| EASI-75 | 68% Diff: +41% | 58% Diff: +32% | 27% |
| PP-NRS4 at Week 2 (≥4-pt improvement in itch) | 30% | 14% | 8% |
Trial-AD-3 included an active comparator arm: dupilumab 300 mg Q2W SC (initial 600 mg, then 300 mg Q2W) + background TCS. Differences from placebo are approximate from label Table 10 (95% CI: 200 mg IGA: 25%–42%; EASI-75: 32%–51%). Source: FDA PI NDA 213871, Section 14.
Safety & Adverse Drug Reactions
Placebo-Controlled Pool · Weeks 0–16 · Section 6.1Total Exposed (All Trials)
1,623
Moderate-to-severe AD; 1,428 patient-years of exposure; 634 subjects with ≥1 year
Placebo-Controlled Pool
1,198
608 on 100 mg · 590 on 200 mg · up to 16 weeks; plus 342 placebo subjects
Overall Infection Rate (16 wk)
168.8
Per 100 PY (100 mg); 159.5/100PY (200 mg) vs 126.8/100PY placebo
Discontinuation due to AEs
5.1%
61/1,198 subjects treated with Abrocitinib discontinued due to adverse reactions
Adverse Reactions ≥1% (Weeks 0–16, Placebo-Controlled)
Table 3, Section 6.1 — Study-size adjusted percentages| Adverse Reaction | Abrocitinib 200 mg (N=590) | Abrocitinib 100 mg (N=608) | Placebo (N=342) |
|---|---|---|---|
| Nausea | 14.5% (86/590) | 6.0% (37/608) | 2.1% |
| Nasopharyngitis | 8.7% (51/590) | 12.4% (75/608) | 7.9% |
| Headache | 7.8% (46/590) | 6.0% (36/608) | 3.5% |
| Acne | 4.7% (28/590) | 1.6% (10/608) | 0% |
| Herpes simplex (incl. oral, ophthalmic, genital) | 4.2% (25/590) | 3.3% (20/608) | 1.8% |
| Vomiting | 3.2% (19/590) | 1.5% (9/608) | 0.9% |
| Increased blood CPK | 2.9% (17/590) | 2.3% (14/608) | 1.5% |
| Dizziness | 2.9% (17/590) | 1.8% (11/608) | 0.9% |
| Urinary tract infection | 2.2% (13/590) | 1.7% (10/608) | 1.2% |
| Abdominal pain upper | 1.9% (11/590) | 0.6% (4/608) | 0% |
| Thrombocytopenia | 1.5% (9/590) | 0% (0/608) | 0% |
| Herpes zoster | 1.2% (7/590) | 0.3% (2/608) | 0% |
| Fatigue | 1.3% (8/590) | 1.6% (10/608) | 0.5% |
| Impetigo | 0.5% (3/590) | 1.5% (9/608) | 0.3% |
| Influenza | 1.1% (6/590) | 1.2% (7/608) | 0% |
| Hypertension | 0.8% (5/590) | 1.2% (7/608) | 0.7% |
Notable Safety Signals
Serious Infections (16 wk, placebo-controlled)
100 mg: 6 subjects (3.9/100PY) · 200 mg: 2 subjects (1.3/100PY) · Placebo: 2 subjects (2.6/100PY). Most common: herpes simplex, herpes zoster, pneumonia. Long-term: 2.3/100PY for both doses.
Herpes Zoster (all 5 trials incl. LTE)
200 mg: 35 subjects (5.2/100PY) · 100 mg: 16 subjects (2.0/100PY) · Placebo: 0 subjects. Geriatric patients (≥65 years) had higher HZ rate: 7.40/100PY vs 3.44/100PY in younger adults.
Thrombocytopenia (dose-dependent)
Transient, dose-dependent decrease in platelet count. Nadir at median 24 days after 200 mg. ~40% recovery by 12 weeks without discontinuation. Thrombocytopenia AE: 200 mg 0.9/100PY; 100 mg: none. Contraindicated with antiplatelet drugs (first 3 months).
Thrombosis (PE/DVT — all trials)
PE: 3 subjects (0.4/100PY) — all 200 mg. DVT: 2 subjects (0.3/100PY) — all 200 mg. No thrombosis in 100 mg arm. Boxed warning for thrombosis risk consistent with JAK inhibitor class.
MACE (all 5 trials)
100 mg: 1 subject (0.1/100PY) · 200 mg: 2 subjects (0.3/100PY). Boxed warning: higher MACE rates with another JAK inhibitor vs TNF blockers in RA (Abrocitinib not approved for RA).
Lipid Elevations (dose-dependent)
Dose-related increase in LDL-c, total cholesterol, and HDL-c from Week 4, maintained through final visit. Hyperlipidemia AE: 100 mg 0.6/100PY · 200 mg 2.0/100PY. Monitor lipids at ~4 weeks.
Retinal Detachment
16-wk placebo-controlled: 1 subject (0.6/100PY) on 100 mg. All 5 trials: 2 subjects (0.3/100PY) on 100 mg. Advise patients to report sudden vision changes immediately.
Malignancy (all 5 trials incl. LTE)
100 mg: 4 subjects (0.5/100PY) · 200 mg: 2 subjects (0.3/100PY). No malignancy in 16-wk placebo-controlled period for placebo or 100 mg arm; 1 subject (0.65/100PY) on 200 mg.
Lymphopenia (ALC <500/mm³)
200 mg: 2 subjects (1.2/100PY) at 16 weeks — both in first 4 weeks. No cases in 100 mg or placebo. Among all exposed: confirmed ALC <500 occurred only in patients ≥65 years old.
CPK Elevations
200 mg: 12.3/100PY · 100 mg: 6.9/100PY · Placebo: 7.5/100PY. Most elevations transient. No rhabdomyolysis reported.
Geriatric safety note (Section 8.5): 145 patients ≥65 years enrolled (4.6%). Higher proportion of elderly patients discontinued vs younger adults. Herpes zoster incidence in elderly: 7.40/100PY vs 3.44/100PY in adults <65 years. Higher proportion of elderly had platelet counts <75,000/mm³. Confirmed ALC <500/mm³ occurred only in patients ≥65 years across all exposed subjects.
Pharmacokinetics
Section 12.3 — Prescribing InformationRoute / Bioavailability
~60%
Oral; >91% extent of absorption; absolute oral bioavailability ~60%
Tmax
~1 hour
Peak plasma concentrations reached within 1 hour; delayed by 2 hrs with high-fat meal (not clinically significant)
Dose Proportionality
Linear
Cmax and AUC increase dose-proportionally up to 200 mg; steady-state within 48 hours
Volume of Distribution (Vd)
~100 L
After IV administration; distributes equally between red blood cells and plasma
Protein Binding
64%
Abrocitinib: 64% · M1: 37% · M2: 29% bound to plasma proteins (predominantly albumin)
Elimination Half-Life
3–5 hours
Mean t½ of abrocitinib and active metabolites M1 and M2; eliminated primarily by metabolic clearance
PK Properties Summary
| PK Parameter | Value / Finding |
|---|---|
| Absorption extent | >91% oral absorption; absolute bioavailability ~60% |
| Effect of food | High-fat meal: AUC ↑26%, Cmax ↑29%, Tmax prolonged 2 hrs — no clinically relevant effect; may take with or without food |
| Steady state | Achieved within 48 hours of once-daily dosing |
| Metabolism | CYP2C19 (~53%), CYP2C9 (~30%), CYP3A4 (~11%), CYP2B6 (~6%); two active metabolites: M1 (3-hydroxypropyl, less active) and M2 (2-hydroxypropyl, equipotent to parent) |
| Active metabolites | M1 (~10%) + M2 (~30%) + parent (~60%) contribute to pharmacologic activity; sum of unbound potency-adjusted exposures = “combined exposure” |
| Excretion | <1% unchanged drug in urine; M1 and M2 excreted predominantly in urine via OAT3 transporter |
| CYP2C19 poor metabolizers | AUC of abrocitinib 2.3-fold higher vs normal metabolizers; 3–5% of Caucasians/Blacks and 15–20% of Asians are CYP2C19 PMs — dose reduction required |
| Moderate renal impairment (eGFR 30–59) | Combined exposure (AUCinf,u) ↑110% vs normal renal function — dose reduction to 50 mg QD required |
| Severe renal impairment (eGFR <30) | Combined exposure ↑191% — Abrocitinib not recommended (ESRD included) |
| Mild hepatic impairment (Child Pugh A) | Combined exposure ↓4% vs normal — no dose adjustment |
| Moderate hepatic impairment (Child Pugh B) | Combined exposure ↑15% vs normal — no dose adjustment |
| Severe hepatic impairment (Child Pugh C) | Not studied — avoid use |
| Body weight, sex, race, age | No clinically meaningful effect on Abrocitinib exposure |
| CYP inhibition/induction (in vitro) | Abrocitinib, M1, M2 are not inhibitors or inducers of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4; not inhibitors of UGTs |
| Transporter | Inhibitor of OCT1; not an inhibitor of OATP1B1/1B3, BSEP, OAT1, or OCT2 |
| P-gp interaction | Single dose Abrocitinib 200 mg ↑dabigatran AUC ~53%, Cmax ~40% (P-gp substrate); monitor narrow therapeutic index P-gp substrates (e.g., digoxin) |
| Cardiac electrophysiology | No clinically relevant QT prolongation at 3× maximum recommended dose |
Pharmacodynamics
Section 12.2| PD Parameter | Finding |
|---|---|
| hsCRP | Dose-dependent reduction; returns to near baseline within 4 weeks of discontinuation |
| IL-31 (pruritus mediator) | Dose-dependent reduction; important mediator of itch in AD |
| TARC (CCL17) | Dose-dependent reduction; Th2 chemokine marker of AD activity |
| Platelet count effect | Transient, dose-dependent decrease; nadir at median 24 days (200 mg); ~40% recovery by 12 weeks without DC; greater nadir with lower baseline platelet count |
Drug Interaction Studies (Key DDIs)
Tables 6 & 7, Section 12.3| Interacting Drug | Effect on Combined Abrocitinib Exposure (AUCinf,u) | Clinical Action |
|---|---|---|
| Fluvoxamine (strong CYP2C19 + mod CYP3A inhibitor) | AUC ↑1.91-fold (90% CI: 1.74–2.10) | Reduce dose to 50 mg QD; may escalate to 100 mg if inadequate response |
| Fluconazole (strong CYP2C19 + mod CYP2C9/3A inhibitor) | AUC ↑2.55-fold (parent alone ↑4.8-fold) | Avoid concomitant use (moderate-to-strong inhibitor of both CYP2C19 and CYP2C9) |
| Rifampin (strong CYP inducer) | AUC ↓0.44-fold (56% reduction) | Avoid concomitant use with strong CYP2C19 or CYP2C9 inducers |
| Probenecid (OAT3 inhibitor) | AUC ↑1.66-fold | Not considered clinically significant |
| Dabigatran (P-gp substrate, sensitive) | Dabigatran AUC ↑53%, Cmax ↑40% | Monitor/titrate narrow TI P-gp substrates (e.g., digoxin); dabigatran interaction not clinically significant |
Dosing & Administration
Sections 2.1–2.7Standard Dosing Regimen
- Start: 100 mg orally once daily (with or without food)
- If inadequate response at Week 12 → increase to 200 mg once daily
- If inadequate response after dose increase to 200 mg → discontinue therapy
- Can be used with or without topical corticosteroids
- Swallow whole with water — do not crush, split, or chew
- Missed dose: take ASAP unless <12 hours to next dose; skip and resume
Pre-Treatment Evaluations Required
- TB evaluation (latent TB screen — IGRA or TST)
- Viral hepatitis screening (HBV, HCV) per clinical guidelines
- CBC — do not initiate if platelets <150,000/mm³, ALC <500/mm³, ANC <1,000/mm³, or Hb <8 g/dL
- Complete all age-appropriate immunizations including herpes zoster vaccine prior to start
- Lipid panel at baseline; reassess at ~4 weeks
Dose Modifications — Special Populations
- Mild renal (eGFR 60–89): 100 mg QD (standard)
- Moderate renal (eGFR 30–59): 50 mg QD; may increase to 100 mg if inadequate response at 12 weeks
- Severe renal / ESRD: Not recommended
- Mild or moderate hepatic impairment (Child Pugh A/B): No dose adjustment
- Severe hepatic impairment (Child Pugh C): Avoid use
- CYP2C19 poor metabolizers: Start 50 mg QD; may increase to 100 mg QD after 12 weeks if inadequate response
- Strong CYP2C19 inhibitors: Reduce to 50 mg QD
Hematologic Discontinuation Thresholds
- Platelets <50,000/mm³: Discontinue; restart when >100,000/mm³
- ALC <500/mm³: Temporarily discontinue; restart when ALC returns above threshold
- ANC <1,000/mm³: Temporarily discontinue; restart when ANC returns above threshold
- Hb <8 g/dL: Temporarily discontinue; restart when Hb returns above threshold
- CBC monitoring: baseline, 4 weeks after start, 4 weeks after dose increase
Contraindications
Section 4- Antiplatelet therapies (except low-dose aspirin ≤81 mg daily) during the first 3 months of Abrocitinib treatment — risk of bleeding with thrombocytopenia
Warnings & Precautions
Section 5- Serious Infections (5.1): Increased risk including TB, invasive fungal infections, herpes zoster, herpes simplex, pneumonia, viral reactivation. Screen for TB and viral hepatitis before initiation. Avoid in active infection. If serious infection develops, discontinue.
- Mortality (5.2): Higher rate of all-cause mortality, including sudden CV death, observed with another JAK inhibitor vs TNF blockers in RA patients ≥50 years with ≥1 CV risk factor. Abrocitinib not approved for RA.
- Malignancy & Lymphoproliferative Disorders (5.3): Lymphoma, NMSC, and other malignancies reported. Higher rate of malignancy with another JAK inhibitor vs TNF blockers in RA. Perform periodic skin examinations; limit UV exposure.
- Major Adverse Cardiovascular Events (5.4): MACE reported in AD trials. Boxed warning for class risk. Discontinue if MI or stroke occurs. Counsel especially current/past smokers.
- Thrombosis (5.5): DVT and PE observed (200 mg only in AD trials). Avoid in patients at increased thrombosis risk. Discontinue if symptoms of thrombosis occur.
- Laboratory Abnormalities (5.6): Thrombocytopenia, lymphopenia, dose-dependent lipid elevations. Monitor CBC at baseline, 4 wks, and after dose increase. Monitor lipids at ~4 wks.
- Immunizations (5.7): Avoid live vaccines immediately prior to, during, and immediately after Abrocitinib therapy. Complete all vaccinations including herpes zoster vaccine before starting.
Use in Special Populations
Section 8| Population | Recommendation |
|---|---|
| Pregnancy | Insufficient data to establish drug-associated risk. Pregnancy registry: 1-877-311-3770. Animal data: skeletal variations in rats at 14× MRHD; maternal dystocia at 14× MRHD; embryofetal lethality at 22× MRHD. No effects in rabbits up to 5× MRHD. |
| Lactation | Not recommended during treatment and for 1 day after last dose (~5–6 half-lives). AUC in rat milk ~5× plasma. No human data. |
| Females of reproductive potential | May impair female fertility (reversible in rats within 1 month of cessation). Counsel patients. |
| Pediatric (<18 years) | Safety and effectiveness not established. Irreversible bone findings (femoral head abnormalities) in juvenile rats at all dose levels — concern for pediatric use. |
| Geriatric (≥65 years) | 145 patients ≥65 enrolled (4.6%). Higher discontinuation rate. Higher herpes zoster incidence (7.40 vs 3.44/100PY). ALC <500 only in ≥65 group. Higher proportion with platelets <75,000/mm³. |
| Renal impairment | Mild: standard dose. Moderate: 50 mg QD. Severe/ESRD: not recommended. Not studied in renal replacement therapy. |
| Hepatic impairment | Mild (A)/moderate (B): no adjustment. Severe (C): avoid. |
| CYP2C19 poor metabolizers | AUC 2.3-fold higher. Start 50 mg QD; may escalate to 100 mg QD if inadequate response. ~3–5% Caucasians/Blacks; ~15–20% Asians. |
Regulatory History
NDA 213871 · Pfizer Labs · Reference ID: 4920574Application Type
NDA
New Drug Application — small molecule oral therapy
Review Designation
Standard Review
No Priority Review or Breakthrough Therapy designation noted in label
Approval Date
Jan 14, 2022
Initial U.S. approval for moderate-to-severe AD in adults
Label Revision
01/2022
Prescribing information revised January 2022 — verify current label at FDA.gov
Regulatory Timeline
2019–2021
Phase 3 Clinical Program
Three pivotal randomized controlled trials conducted: Trial-AD-1 (NCT03349060), Trial-AD-2 (NCT03575871) — monotherapy; Trial-AD-3 (NCT03720470) — combination with topical corticosteroids including dupilumab active comparator arm. Total 1,615 subjects enrolled.
2021 · Pre-Approval
NDA 213871 Submission
Pfizer Inc. submitted NDA for abrocitinib (CIBINQO) for refractory moderate-to-severe atopic dermatitis in adults. Data package included 3 pivotal trials and long-term extension safety data (1,623 subjects, 1,428 patient-years).
January 14, 2022
FDA Approval — Abrocitinib (abrocitinib) Tablets
Approved for adults with refractory, moderate-to-severe atopic dermatitis not adequately controlled with other systemic drug products including biologics, or when use of those therapies is inadvisable. Available as 50 mg, 100 mg, and 200 mg tablets. NDC: 0069-0335-30 (100 mg, 30-count bottle).
January 2022
Prescribing Information Published (Ref ID: 4920574)
Initial U.S. prescribing information issued including Boxed Warning for serious infections, mortality, malignancy, MACE, and thrombosis. Co-approved on same date as upadacitinib (Rinvoq) for AD indication — first two oral JAK inhibitors approved for AD on the same day.
Ongoing
Post-Marketing Commitments
Long-term extension trial safety data collection ongoing. Pregnancy exposure registry active (1-877-311-3770). Pediatric development program ongoing — pediatric use not currently approved; irreversible juvenile bone findings limit pediatric labeling.
Key Regulatory Reference Documents
| Document | Reference / Source |
|---|---|
| Prescribing Information (Label) | NDA 213871 · Ref ID: 4920574 · Revised 01/2022 |
| Drugs@FDA | NDA 213871 — Drugs@FDA |
| Pivotal Trial — Monotherapy 1 | Trial-AD-1 · NCT03349060 · ClinicalTrials.gov |
| Pivotal Trial — Monotherapy 2 | Trial-AD-2 · NCT03575871 · ClinicalTrials.gov |
| Pivotal Trial — Combination | Trial-AD-3 · NCT03720470 · ClinicalTrials.gov (includes dupilumab active comparator) |
| Manufacturer | Pfizer Labs, Division of Pfizer Inc. · New York, NY 10017 |
| NDC (100 mg, 30-count) | 0069-0335-30 |
| NDC (200 mg, 30-count) | 0069-0435-30 |
| NDC (50 mg, 30-count) | 0069-0235-30 |
| Storage | 20°C–25°C (68°F–77°F); excursions 15°C–30°C permitted; child-resistant container |
Nonclinical Toxicology Summary
Section 13.1| Study | Finding |
|---|---|
| Carcinogenicity (2-year oral — rats) | Increased benign thymomas in female rats at 10 mg/kg/day (4× MRHD) and 30 mg/kg/day (19× MRHD). Not carcinogenic in female rats at 3 mg/kg/day (0.8× MRHD) or male rats at all doses up to 30 mg/kg/day. |
| Carcinogenicity (Tg.rasH2 mice) | Not carcinogenic at up to 60 mg/kg/day (males) and 75 mg/kg/day (females). |
| Mutagenicity | Not mutagenic in Ames assay. Aneugenic in in vitro TK6 micronucleus assay — but NOT aneugenic/clastogenic in in vivo rat bone marrow micronucleus assay. |
| Male fertility (rats) | No impairment at doses up to 70 mg/kg/day (35× MRHD). |
| Female fertility (rats) | Impaired at 70 mg/kg/day (39× MRHD) — reduced fertility index, corpora lutea, implantation sites. Reversible within 1 month of cessation. No impairment at 10 mg/kg/day (3× MRHD). |
| Embryofetal development (rats) | Skeletal variations at 30 mg/kg/day (14× MRHD); increased embryofetal lethality and additional skeletal variations at 60 mg/kg/day (22× MRHD). No malformations. |
| Embryofetal development (rabbits) | No maternal or developmental toxicity up to 75 mg/kg/day (5× MRHD). |
| Pre-/postnatal development (rats) | Maternal dystocia and reduced offspring weight at 30 mg/kg/day (14× MRHD). Postnatal survival markedly decreased at 60 mg/kg/day (22× MRHD). No effects at 10 mg/kg/day (3× MRHD). |
| Juvenile animal toxicology (rats) | Reversible decrease in primary spongiosa. Irreversible femoral head abnormalities (small/misshapen) at all doses ≥5 mg/kg/day (1.1× MRHD). Irreversible femur size decrease, paw malrotation, limb impairment at ≥25 mg/kg/day. Bone findings not observed in older animals. |
Data sourced directly from FDA Prescribing Information (NDA 213871, Ref ID 4920574, Revised 01/2022). This label may not be the latest approved by FDA — for current labeling visit https://www.fda.gov/drugsatfda. TrialistMD provides clinical research intelligence for educational purposes only.
Baseline Characteristics — Pivotal Clinical Trials
Section 14 · NDA 213871 · Trial-AD-1, AD-2, AD-3Total Randomized
1,615
Across 3 pivotal trials (Trial-AD-1 N=387 · AD-2 N=391 · AD-3 N=837)
Mean Baseline Age
36 years
8% aged 12–<18 (adolescents; not approved) · 6.1% aged ≥65 years
Mean Baseline EASI
30
64% IGA 3 (moderate) · 36% IGA 4 (severe)
Prior Systemic Therapy
>40%
In each trial; 6% prior dupilumab in AD-1 and AD-2
Trial Design Overview
| Feature | Trial-AD-1 (NCT03349060) | Trial-AD-2 (NCT03575871) | Trial-AD-3 (NCT03720470) |
|---|---|---|---|
| Regimen type | Monotherapy | Monotherapy | Combination + background TCS |
| Duration | 12 weeks | 12 weeks | 16 weeks |
| Total N randomized | 387 | 391 | 837 |
| Abrocitinib 200 mg QD | N=154 | N=155 | N=226 |
| Abrocitinib 100 mg QD | N=156 | N=158 | N=238 |
| Placebo | N=77 | N=78 | N=131 |
| Active comparator | None | None | Dupilumab 300 mg Q2W SC (initial 600 mg Day 1) N=242 |
| Background therapy | None (monotherapy) | None (monotherapy) | TCS throughout all arms |
| Age eligibility | ≥12 years | ≥12 years | ≥18 years (adults only) |
| Prior dupilumab allowed | Yes (6% enrolled) | Yes (6% enrolled) | No (dupilumab-naive required) |
| Co-primary endpoints | IGA 0 or 1 (≥2-point reduction from baseline) AND EASI-75 (≥75% improvement from baseline) — both at Week 12 | ||
Demographic & Disease Baseline Characteristics
Placebo-Controlled Safety Pool · Section 6.1 & Section 14| Characteristic | Trial-AD-1 (N=387) | Trial-AD-2 (N=391) | Trial-AD-3 (N=837) |
|---|---|---|---|
| Mean age (years) | 36 years overall | ||
| Subjects aged 12–<18 years | Included (~8%) | Included (~8%) | Not enrolled |
| Subjects aged ≥65 years | 6.1% (94 subjects) across placebo-controlled pool | ||
| Male | 53% overall | ||
| Race — White | 69% overall (68.7% in safety pool) | ||
| Baseline IGA 3 (moderate AD) | 64% overall | ||
| Baseline IGA 4 (severe AD) | 36% overall | ||
| Mean baseline EASI score | 30 | ||
| BSA involvement required | ≥10% at baseline | ||
| Peak Pruritus NRS (PP-NRS) required | ≥4 at baseline (moderate-to-severe itch) | ||
| Prior systemic AD therapy | >40% | >40% | >40% |
| Prior dupilumab exposure | 6% | 6% | 0% (excluded) |
| Eligibility — prior therapy | Inadequate response to prior topical therapy, or topical therapy medically inadvisable, or prior systemic therapy failure | ||
Safety Population Baseline (Placebo-Controlled Pool)
Section 6.1 · N=1,540 (1,198 Abrocitinib + 342 placebo)| Characteristic | Abrocitinib 200 mg (N=590) | Abrocitinib 100 mg (N=608) | Placebo (N=342) |
|---|---|---|---|
| Median age (years) | 33.0 years | ||
| Subjects aged 12–<18 years | 124 subjects (8.1%) | ||
| Subjects aged ≥65 years | 94 subjects (6.1%) | ||
| Male | 53.9% | ||
| Race — White | 68.7% | ||
| Exposure duration | Up to 16 weeks placebo-controlled; 1,198 total subjects | Up to 16 weeks | |
| Total Abrocitinib exposure (all 5 trials) | 1,623 subjects · 1,428 patient-years · 634 subjects with ≥1 year exposure | ||
Subgroup analysis: Examination of age, gender, race, body weight, and previous systemic AD therapy (including prior dupilumab) did not identify clinically meaningful differences in response to Abrocitinib 100 mg or 200 mg QD among these subgroups in Trial-AD-1, Trial-AD-2, and Trial-AD-3.
Source: FDA Prescribing Information NDA 213871, Sections 6.1 and 14, Ref ID 4920574, Revised 01/2022. Trial-AD-3 enrolled adults only (≥18 years); Trial-AD-1 and AD-2 enrolled subjects ≥12 years — Abrocitinib is not approved for use in pediatric patients. Dupilumab arm in Trial-AD-3: initial dose 600 mg Day 1, then 300 mg Q2W SC.
