Leqselvi Drug Information
Generic name: DEURUXOLITINIB PHOSPHATE
Uses of Leqselvi
LEQSELVI™ is indicated for the treatment of adult patients with severe alopecia areata. Limitations of Use LEQSELVI is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants. LEQSELVI is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with severe alopecia areata.
Dosage & Administration of Leqselvi
Recommended Evaluations and Immunizations Prior to and During Treatment Perform the following prior to treatment with LEQSELVI: CYP2C9 genotype determination: Test patients for CYP2C9 variants to determine CYP2C9 genotype. LEQSELVI is contraindicated in patients who are CYP2C9 poor metabolizers (patients with decreased cytochrome P450 (CYP) 2C9 function). An FDA-cleared or -approved test for the detection of CYP2C9 variants to direct the use of LEQSELVI is not currently available.
Evaluation for use of concomitant CYP2C9 inhibitors: LEQSELVI is contraindicated in patients taking moderate or strong CYP2C9 inhibitors. Active and latent tuberculosis (TB) evaluation: LEQSELVI treatment 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 of TB, start preventive therapy for TB prior to LEQSELVI treatment.
Viral hepatitis screening in accordance with clinical guidelines: LEQSELVI treatment is not recommended in patients with active hepatitis B or hepatitis C. Hepatitis B infection screening: If hepatitis B infection is discovered, follow hepatitis B clinical guidelines, or refer to a liver specialist. Monitor patients for reactivation in accordance with clinical guidelines during treatment.
Monitor complete blood counts periodically during treatment and modify dosage as recommended. Complete any necessary immunizations, including herpes zoster vaccinations, according to current immunization guidelines prior to LEQSELVI treatment.
Recommended Dosage
The recommended dosage of LEQSELVI for the treatment of severe alopecia areata is 8 mg orally twice daily, with or without food. If a dose is missed, skip the missed dose and resume dosing at the next scheduled dose.
Treatment Interruption and Resumption Serious or Opportunistic Infections If a patient develops a serious or opportunistic infection, interrupt LEQSELVI treatment until the infection is controlled. Hematological Abnormalities Recommendations for LEQSELVI treatment interruption for hematologic abnormalities are described in Table 1. Table 1: Recommendations for LEQSELVI Treatment Interruption for Hematologic Abnormalities and Resumption
| Laboratory Measure | Interruption Criterion | Resumption Criterion |
|---|---|---|
| Absolute Lymphocyte Count (ALC) | <500 cells/mm 3 | ≥500 cells/mm 3 |
| Absolute Neutrophil Count (ANC) | <1000 cells/mm 3 | ≥1000 cells/mm 3 |
| Hemoglobin | <8 g/dL | ≥8 g/dL |
Side Effects of Leqselvi
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 LEQSELVI was evaluated in three randomized, placebo-controlled clinical trials (including a dose-ranging trial), two open-label trials, and two long-term extension trials in adult subjects with severe alopecia areata. These subjects had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT) for more than six months.
A total of 1,730 subjects with alopecia areata were treated across all trials, representing 1,962.9 patient-years of exposure. Deuruxolitinib 12 mg is not approved. A total of 20 (3.1%) of subjects treated with LEQSELVI 8 mg were discontinued from the trials due to adverse reactions.
| a. %-study size adjusted percentages. b. Acne includes: acne, dermatitis acneiform, and acne pustular. c. Hyperlipidemia includes: blood cholesterol increased, low density lipoprotein increased, blood triglycerides increased, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, and dyslipidaemia. d. Fatigue includes: fatigue, asthenia, hypersomnia, somnolence, and lethargy. e. Skin and soft issue infections includes: folliculitis, impetigo, skin infection, subcutaneous abscess, furuncle, paronychia, and pustule. f. Anemia includes: anemia, hematocrit decreased, hemoglobin decreased, iron deficiency anemia, and red blood cell count decreased. g. Neutropenia includes: neutropenia and neutrophil count decreased. h. Thrombocytosis includes: thrombocytosis and platelet count increased. i. Herpes includes: oral herpes, herpes simplex, genital herpes simplex, and nasal herpes. | |||
| Placebo N = 299 n (%) a | LEQSELVI 8 mg twice daily N = 640 n (%) a | Deuruxolitinib 12 mg twice daily N = 380 n (%) a | |
| Acne b | 13 (4.3) | 66 (10.0) | 52 (12.6) |
| Headache | 30 (9.4) | 83 (12.4) | 44 (10.5) |
| Nasopharyngitis | 21 (6.7) | 54 (8.1) | 33 (7.7) |
| Blood creatine phosphokinase increased | 7 (2.2) | 35 (5.3) | 27 (7.4) |
| Hyperlipidemia c | 10 (3.1) | 30 (4.4) | 19 (5.2) |
| Fatigue d | 12 (3.9) | 26 (3.9) | 20 (4.9) |
| Skin and soft tissue infections e | 2 (0.8) | 11 (1.6) | 15 (4.0) |
| Anemia f | 3 (1.0) | 18 (2.6) | 16 (3.4) |
| Weight increased | 4 (1.4) | 19 (2.9) | 10 (2.5) |
| Neutropenia g | 3 (0.7) | 10 (1.4) | 10 (2.8) |
| Lymphopenia | 2 (0.6) | 2 (0.3) | 7 (2.0) |
| Thrombocytosis h | 0 | 18 (2.7) | 6 (1.6) |
| Herpes i | 2 (0.6) | 8 (1.2) | 6 (1.6) |
Warnings & Cautions for Leqselvi
Serious Infections
Serious infections have been reported in subjects with alopecia areata receiving LEQSELVI. Avoid use of LEQSELVI in patients with an active, serious infection including localized infections. Prior to LEQSELVI treatment, consider the risks and benefits in patients: with chronic or recurrent infection who have been exposed to tuberculosis with a history of a serious or opportunistic infection who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or 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 LEQSELVI.
If the patient develops a serious infection, interrupt treatment with LEQSELVI until the infection resolves or is adequately treated. If a patient develops a new infection during treatment with LEQSELVI, initiate complete diagnostic testing appropriate for an immunocompromised patient and appropriate antimicrobial therapy. Tuberculosis Evaluate patients for latent and active tuberculosis (TB) infection prior to LEQSELVI treatment.
LEQSELVI is not recommended for use in patients with active TB. Treat patients with latent TB before LEQSELVI treatment. Consider anti-TB therapy prior to LEQSELVI treatment in patients with previously untreated latent TB or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection.
Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients receiving LEQSELVI for signs and symptoms of active TB during treatment, including patients who tested negative for latent TB infection prior to treatment. Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) were reported in clinical trials with LEQSELVI.
If a patient develops herpes zoster, consider interrupting LEQSELVI treatment until the episode resolves. The impact of LEQSELVI on chronic viral hepatitis reactivation is unknown. Subjects with positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), or hepatitis C virus (HCV) with detectable HCV RNA at screening were excluded from LEQSELVI clinical trials.
Perform screening for viral hepatitis before treatment with LEQSELVI. If non-active hepatitis B infection is discovered, monitoring for reactivation or prophylactic treatment is recommended. Follow hepatitis B clinical guidelines or refer to a liver specialist.
Hepatitis B viral load (HBV-DNA titer) increase, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, has been reported in subjects with chronic HBV infections receiving JAK inhibitors used to treat inflammatory conditions. The effect of LEQSELVI on viral replication in patients with chronic HBV infection is unknown.
Mortality In a large, randomized, postmarketing safety trial of another JAK inhibitor in rheumatoid arthritis (RA) subjects 50 years and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in subjects treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to and during treatment with LEQSELVI.
Malignancy and Lymphoproliferative Disorders Malignancies were observed in clinical trials of LEQSELVI. In a large, randomized, postmarketing safety trial of another JAK inhibitor in subjects with RA, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in subjects 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 trial, current or past smokers had an additional increased risk of overall malignancies. Non-melanoma skin cancers Non-melanoma skin cancers (NMSCs) have been reported in patients treated with LEQSELVI. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Major Adverse Cardiovascular Events (MACE) In a large, randomized, postmarketing safety trial of another JAK inhibitor in subjects with RA 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. Patients who are current or past smokers are at additional increased risk. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur.
Discontinue LEQSELVI in patients that have experienced a myocardial infarction or stroke.
Thrombosis
Thrombosis, including pulmonary embolism (PE), deep vein thrombosis (DVT) and cerebral venous sinus thrombosis (CVT) have been reported in clinical trials of deuruxolitinib. There was no clear relationship between platelet count elevations and thrombotic events. Thrombosis, including DVT, PE, and arterial thrombosis have been reported in subjects 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 trial of another JAK inhibitor in subjects with RA 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. Avoid LEQSELVI in patients who may be at increased risk of thrombosis.
If symptoms of thrombosis occur, discontinue LEQSELVI and evaluate and treat patients appropriately.
Increased Risk of LEQSELVI-Associated Serious Adverse Reactions in CYP2C9 Poor Metabolizers or with Concomitant Use of Moderate or Strong CYP2C9 Inhibitors Higher plasma concentrations of deuruxolitinib, which may increase the risk of LEQSELVI-associated serious adverse reactions such as thrombosis, may occur when LEQSELVI is used in patients who: Are CYP2C9 poor metabolizers. Are on a concomitant moderate or strong CYP2C9 inhibitor. Prior to LEQSELVI treatment, test patients for CYP2C9 variants to determine if they are poor metabolizers.
An FDA-cleared or -approved test for the detection of CYP2C9 variants to direct the use of LEQSELVI is not currently available. LEQSELVI is contraindicated in patients who are CYP2C9 poor metabolizers or patients who are on concomitant moderate or strong CYP2C9 inhibitors.
Gastrointestinal Perforations
Gastrointestinal perforations have been reported in clinical trials with LEQSELVI. Monitor patients treated with LEQSELVI who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Evaluate promptly patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation.
Hypoglycemia in Patients with Diabetes
Hypoglycemia, including severe hypoglycemia, has been reported following initiation of JAK inhibitors in patients with diabetes. During treatment with LEQSELVI, consider increased monitoring of blood glucose in patients with diabetes. Advise patients with diabetes to contact their healthcare provider(s) if they experience signs or symptoms consistent with hypoglycemia.
Lipid Elevations, Anemia, Neutropenia, and Lymphopenia Perform a CBC prior to and periodically during treatment with LEQSELVI. Lipid Elevations Treatment with LEQSELVI was associated with increases in triglycerides and total cholesterol, including HDL-C and LDL-C. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.
Perform assessment of lipid parameters at baseline and periodically during treatment with LEQSELVI. Manage patients according to clinical guidelines for hyperlipidemia. Anemia Treatment with LEQSELVI was associated with an increased incidence of anemia (hemoglobin less than 8 g/dL) compared to placebo.
Avoid or interrupt LEQSELVI treatment in patients with hemoglobin less than 8 g/dL. Neutropenia Treatment with LEQSELVI was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm 3 ) compared to placebo. Avoid or interrupt LEQSELVI treatment in patients with an ANC less than 1,000 cells/mm 3.
Lymphopenia Treatment with LEQSELVI was associated with an increased incidence of lymphopenia (ALC less than 500 cells/mm 3 ) compared to placebo. Avoid or interrupt LEQSELVI treatment in patients with an ALC less than 500 cells/mm 3.
Immunizations Prior to LEQSELVI treatment, complete all necessary immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in accordance with current immunization guidelines. Avoid use of live vaccines during or immediately prior to LEQSELVI treatment.
Drug Interactions with Leqselvi
- Effect of Other Drugs on LEQSELVI Strong CYP3A and moderate or strong CYP2C9 inducers: Avoid concomitant use of LEQSELVI with strong CYP3A and moderate or strong CYP2C9 inducers. Deuruxolitinib is a CYP2C9 and CYP3A substrate. Concomitant use with a strong CYP3A and moderate or strong CYP2C9 inducer decreases deuruxolitinib exposure (C max and AUC), which may reduce LEQSELVI efficacy.
- Moderate or strong CYP2C9 inhibitors: LEQSELVI is contraindicated in patients taking moderate or strong CYP2C9 inhibitors. Deuruxolitinib is a CYP2C9 substrate. Concomitant use with a moderate or strong CYP2C9 inhibitor is estimated to increase deuruxolitinib exposure (C max and AUC), which may increase the risk of LEQSELVI serious adverse reactions such as thrombosis.
- Moderate or strong CYP2C9 inhibitors: Contraindicated.
Pregnancy Safety for Leqselvi
Pregnancy Risk Summary Based on the findings from animal reproduction studies, deuruxolitinib may cause fetal harm during pregnancy. Available data from pregnancies reported in clinical trials with LEQSELVI are not sufficient to evaluate for a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of deuruxolitinib to pregnant rats during the period of organogenesis at a dose 4.8 times the maximum recommended human dose (MRHD) resulted in reduced fetal weight and increased skeletal malformation.
Oral administration of deuruxolitinib to pregnant rabbits during the period of organogenesis at a dose 0.3 times the MRHD resulted in maternal toxicity, reduced fetal weight, and increased post-implantation loss. Oral administration of deuruxolitinib to pregnant rats during pregnancy and lactation periods at a dose 5 times the MRHD resulted in maternal toxicity, decreased pup survival, and adverse effects on postnatal development (see Data ). Advise pregnant women of the potential risk to a fetus.
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. Data Animal Data In an embryo-fetal development study, deuruxolitinib was administered to pregnant rats during the period of organogenesis at oral doses of 15, 30, and 60 mg/kg/day.
Reduced fetal weight and increased fetal skeletal malformation were noted at 60 mg/kg/day (4.8 times the MRHD based on AUC comparison) with no maternal toxicity. No embryo-fetal toxicity was observed at doses up to 30 mg/kg/day (equivalent to MRHD based on AUC comparison). In another embryo-fetal development study, deuruxolitinib was administered to pregnant rabbits during the period of organogenesis at oral doses of 6, 30, and 60 mg/kg/day.
Reduced fetal weight and increased post-implantation loss were noted at 60 mg/kg/day (0.3 times the MRHD based on AUC comparison), at which maternal toxicity was observed. In a pre- and postnatal development study in rats, deuruxolitinib was administered to pregnant rats during pregnancy and lactation periods at oral doses of 15, 30, and 75 mg/kg/day. Decreases in liveborn pups and pup survival, decreased pup activity and lower pup body weights, and adverse effects on reproductive outcome in the second generation females (decreased corpora lutea, implantation, and number of live embryos, and increased resorption and post-implantation loss) were noted at 75 mg/kg/day (5 times the MRHD based on AUC comparison), at which maternal toxicity was also observed.
No adverse effects on pre- and postnatal development were noted at doses up to 30 mg/kg/day (0.8 times the MRHD based on AUC comparison).
Pediatric Use of Leqselvi
Pediatric Use The safety and effectiveness of LEQSELVI have not been established in pediatric patients.
Contraindications for Leqselvi
LEQSELVI is contraindicated in patients who: Are CYP2C9 poor metabolizers. Are on concomitant moderate or strong CYP2C9 inhibitors. Using moderate or strong CYP2C9 inhibitors.
Overdosage Information for Leqselvi
There is no experience regarding human overdose with LEQSELVI. There is no specific antidote for overdose with LEQSELVI. Treatment should be symptomatic and supportive and monitor patients for signs and symptoms of adverse reactions.
In case of overdose, consider contacting the Poison Center at 1-800-222-1222 for latest recommendations.
Clinical Studies of Leqselvi
Two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials (AA-1 and AA-2 ), evaluated a total of 1,209 adult subjects with alopecia areata (AA), who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT) for more than six months. In both trials, subjects received LEQSELVI 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo twice daily for 24 weeks. Deuruxolitinib 12 mg is not approved.
The trial population ranged from 18 to 65 years of age. At baseline, subjects had average current episode of hair loss of approximately 4 years, with 59% of subjects having complete or near complete scalp hair loss (defined as ≥ 95% scalp hair loss). Approximately 73% of subjects had eyebrow hair involvement and 70% of subjects had eyelash hair involvement.
The primary endpoint for both trials assessed the proportion of subjects who achieved at least 80% scalp hair coverage (SALT score of ≤ 20) at Week 24. Key secondary outcomes included the percentage of responders (defined as “satisfied” or “very satisfied”) at Week 24 on the Satisfaction of Hair Patient-Reported Outcome (SPRO) and the percentage of subjects achieving an absolute SALT score of ≤ 20 at Week Upon completion of the 24-week trials, subjects were eligible to enroll in a long-term extension trial. Clinical Response Assessment of scalp hair loss was based on the SALT score.
Table 3: Clinical Response at Week 24 in Adult Subjects with Severe AA in Table 4: Evaluation of Patient Satisfaction with Scalp Hair Coverage at Weeks 24 in Adult Subjects with Severe AA in Figure 1: Clinical Response over Time in Adult Subjects with Severe AA in Trials AA- 1 and AA-2 The efficacy of LEQSELVI was generally comparable across multiple subgroups including age, gender, and body weight among these subgroups. The results for SALT score ≤ 20 at Week 24 by baseline scalp hair loss severity are presented in Table 5.
| Trial AA-1 | Trial AA-2 | |||
|---|---|---|---|---|
| a Not adjusted for multiplicity. | ||||
| Placebo (N=140) | LEQSELVI 8 mg twice daily (N=351) | Placebo (N=127) | LEQSELVI 8 mg twice daily (N=249) | |
| SALT scores ≤ 20 Common risk difference from Placebo (95% CI) | 1% | 29% 28% (23%, 33%) | 1% | 32% 31% (25%, 37%) |
| SALT scores ≤ 10 Common risk difference from Placebo (95% CI) | 0% a | 20% 21% (16%, 25%) a | 0% a | 24% 24% (19%, 30%) a |
| Trial AA-1 | Trial AA-2 | |||
|---|---|---|---|---|
| a In Trial AA-1, the proportion of responders (defined as subjects who were “satisfied” or “very satisfied”) on LEQSELVI was 42% compared to 5% on placebo. In Trial AA-2, the proportion of responders on LEQSELVI was 46% compared to 2% on placebo. | ||||
| Placebo (N=140) | LEQSELVI 8 mg twice daily (N=351) | Placebo (N=127) | LEQSELVI 8 mg twice daily (N=249) | |
| “Very Satisfied” a | 2% | 19% | 0% | 18% |
| “Satisfied” a | 3% | 23% | 2% | 28% |
| “Neither Satisfied nor Dissatisfied” | 16% | 19% | 13% | 15% |
| “Dissatisfied” | 25% | 18% | 18% | 16% |
| “Very Dissatisfied” | 54% | 21% | 67% | 23% |
| Trials AA-1 and AA-2 | ||
|---|---|---|
| Placebo | LEQSELVI 8 mg BID | |
| 50% to 94% Scalp Hair Loss | ||
| N SALT ≤ 20 | 110 2% | 248 46% |
| 95% to 100% Scalp Hair Loss | ||
| N SALT ≤ 20 | 157 0% | 352 20% |
| BID = twice-daily | ||
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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