Rilzabrutinib

Rilzabrutinib is a small-molecule, covalent, reversible kinase inhibitor targeting Bruton's tyrosine kinase (BTK). Rilzabrutinib mediates its therapeutic effect in ITP through immune modulation including 1) inhibition of B cell activation, and 2) interruption of antibody-coated cell phagocytosis by Fcγ receptor (FcγR) in spleen and liver.

• WAYRILZ is indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. WAYRILZ is a kinase inhibitor indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

• None Nonecontraindicated

See Full Prescribing Information for important recommendations prior to treatment. ( 2.1 , 2.3 ) Recommended dosage: 400 mg orally twice daily; swallow whole with water, with or without food. Do not cut, crush, or chew tablets. ( 2.2 ) 2.1 Recommended Testing Before Initiating WAYRILZ Verify pregnancy status of females of reproductive potential prior to initiating WAYRILZ treatment [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1 , 8.3) ] . 2.2 Recommended Dosage The recommended dosage of WAYRILZ is 400 mg taken orally twice daily. WAYRILZ can be taken at approximately the same time each day with or without food. In patients who experience gastrointestinal symptoms, taking WAYRILZ with food may improve tolerability. Advise patients to swallow tablets whole with a glass of water. Advise patients not to cut, crush or chew the tablets. If a dose is missed, patients should take the missed dose of WAYRILZ as soon as possible on the same day and at least 2 hours apart from the next regular scheduled dose. If taking antacid or histamine H2 receptor antagonist, administer the dose of WAYRILZ at least 2 hours before the antacid or histamine H2 receptor antagonist. 2.3 Monitoring and Dose Modifications for Hepatotoxicity Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with WAYRILZ. For patients who develop abnormal liver tests after WAYRILZ, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If Drug-Induced Liver Injury (DILI) is suspected, withhold WAYRILZ.

Serious Infections: Monitor patients for signs and symptoms of infection, evaluate promptly, and treat. ( 5.1 ) Hepatotoxicity, Including Drug-Induced Liver Injury: Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment. ( 5.2 ) Embryo-Fetal Toxicity: Based on preliminary animal data, WAYRILZ may cause fetal harm. Advise females of reproductive potential of the potential risk and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Serious Infections An increased risk of serious infections (including bacterial, viral, or fungal) can occur in patients treated with Bruton's tyrosine kinase (BTK) inhibitors, including WAYRILZ. In the LUNA-3 trial, fatal pneumonia occurred in one participant in the WAYRILZ group. Other serious infections [one each (0.8%)] included COVID-19 infection, wound infection, and one patient experienced urinary tract infection and kidney abscess. Monitor patients for signs and symptoms of infection and treat appropriately. 5.2 Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, can occur in patients treated with BTK inhibitors. In the clinical trials of WAYRILZ in patients with ITP, elevations of liver transaminases occurred and were generally mild to moderate in severity. Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with WAYRILZ.

The following clinically important adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Hepatotoxicity, Including Drug-Induced Liver Injury [ see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥10%) were diarrhea, nausea, headache, abdominal pain, and COVID-19. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of WAYRILZ was evaluated in a randomized, double-blind (DB), placebo-controlled, parallel-group study (LUNA-3), in which 202 adult patients with persistent or chronic ITP received either WAYRILZ (n=133) or placebo (n=69) [see Clinical Studies (14) ] . During the 24-week DB period, the median duration of WAYRILZ exposure was 98 days (range: 22 to 182). The most common adverse reactions (≥10%) were diarrhea, nausea, headache, abdominal pain, and COVID-19. Adverse reactions resulting in discontinuation of WAYRILZ included erythema nodosum, neutropenia, arthralgia, dyspepsia, headache, pain in extremity, abdominal discomfort, diarrhea, nausea, and pneumonia and occurred in 4.5% of patients. Table 1 presents common adverse reactions from the LUNA-3 Study.

Lactation: Advise not to breastfeed. ( 8.2 ) Hepatic Impairment: Avoid use of WAYRILZ in patients with moderate or severe hepatic impairment. ( 8.6 ) Renal Impairment: Avoid use in patients with severe renal impairment. ( 8.7 ) 8.1 Pregnancy Risk Summary Based on animal data, WAYRILZ may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of rilzabrutinib to pregnant rats and rabbits during organogenesis at exposures 4- to 10-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 400 mg twice daily did not cause adverse developmental effects. However, adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure (based on AUC) at the MRHD ( see Data ). There are no available clinical data on the use of WAYRILZ during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S.

Metabolism

The pharmacokinetics of rilzabrutinib are presented as geometric mean (% coefficient of variation) unless otherwise specified. The C max and AUC of rilzabrutinib increase proportionally following administration of multiple doses of 300 mg to 600 mg.

In the event of overdosage, closely monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

• Aug 29, 2025NDANDA219685Genzyme Corp

1. 1Diarrhoea5829%
2. 2Platelet Count Decreased5226%
3. 3Nausea4523%
4. 4Drug Ineffective2010%
5. 5Fatigue189.0%
6. 6Headache189.0%
7. 7Abdominal Discomfort157.5%
8. 8Vomiting136.5%
9. 9Dizziness115.5%
10. 10Epistaxis105.0%
11. 11Platelet Count Abnormal94.5%
12. 12Asthenia84.0%
13. 13Abdominal Pain Upper73.5%
14. 14Pain73.5%
15. 15Product Use In Unapproved Indication73.5%

The 10 most recently updated of 20 ClinicalTrials.gov registrations naming Rilzabrutinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease
  Recruiting · Phase 2 · Interventional · 84 enrolled · Sanofi
  NCT06500702updated 2026-06-08
• Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA)
  Active not recruiting · Phase 2 · Interventional · 22 enrolled · Sanofi
  NCT05002777updated 2026-06-05
• A Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Oral Rilzabrutinib Compared With Placebo in Participants 18 Years of Age and Older With Warm Autoimmune Hemolytic Anemia
  Recruiting · Phase 3 · Interventional · 90 enrolled · Sanofi
  NCT07086976updated 2026-06-04
• A 52-week Study of Rilzabrutinib Efficacy and Safety Compared to Placebo in Adults Diagnosed With IgG4-related Disease
  Recruiting · Phase 3 · Interventional · 124 enrolled · Sanofi
  NCT07190196updated 2026-06-02
• Study to Evaluate the Efficacy and Safety of Oral Rilzabrutinib in Adults With Immune Thrombocytopenia (ITP) Who Failed First-line Treatment
  Recruiting · Phase 3 · Interventional · 60 enrolled · Sanofi
  NCT07007962updated 2026-05-27
• A Study to Investigate the Efficacy and Safety of Rilzabrutinib in Adult Participants With Graves' Disease
  Recruiting · Phase 2 · Interventional · 30 enrolled · Sanofi
  NCT06984627updated 2026-05-22
• The Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease
  Recruiting · Phase 3 · Interventional · 192 enrolled · Sanofi
  NCT06975865updated 2026-05-01
• A Study of Rilzabrutinib in Adult Patients With Immune Thrombocytopenia (ITP)
  Completed · Phase 2 · Interventional · 86 enrolled · Principia Biopharma, a Sanofi Company
  NCT03395210updated 2026-02-23
• Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
  Active not recruiting · Phase 3 · Interventional · 232 enrolled · Principia Biopharma, a Sanofi Company
  NCT04562766updated 2026-02-23
• Rilzabrutinib for the Adult Participants With Chronic ITP Who Have Completed Phase 3 Study in Japan
  Active not recruiting · Phase 3 · Interventional · 4 enrolled · Sanofi
  NCT07216079updated 2025-11-06

Frequently asked questions

How does Rilzabrutinib work?

Rilzabrutinib is a small-molecule, covalent, reversible kinase inhibitor targeting Bruton's tyrosine kinase (BTK). Rilzabrutinib mediates its therapeutic effect in ITP through immune modulation including 1) inhibition of B cell activation, and 2) interruption of antibody-coated cell phagocytosis by Fcγ receptor (FcγR) in spleen and liver.

What is Rilzabrutinib used for?

According to FDA labeling, Rilzabrutinib carries indications including: WAYRILZ is indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. WAYRILZ is a kinase inhibitor indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Rilzabrutinib?

Rilzabrutinib is classified as Kinase Inhibitor, Bile Salt Export Pump Inhibitors, Breast Cancer Resistance Protein Inhibitors, Bruton's Tyrosine Kinase Inhibitors, Cytochrome P450 3A Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, P-Glycoprotein Inhibitors.

What are the brand names for Rilzabrutinib?

Rilzabrutinib is marketed under brand names including Wayrilz.

What are the contraindications for Rilzabrutinib?

Rilzabrutinib labeling lists contraindications including: None None. Always consult the full prescribing information and a clinician.