Fabhalta

     Paroxysmal Nocturnal Hemoglobinuria

FABHALTA is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

     Immunoglobulin A Nephropathy

FABHALTA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g.

This indication is approved under accelerated approval based on reduction of proteinuria. It has not been established whether FABHALTA slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

     Complement 3 Glomerulopathy

FABHALTA is indicated for the treatment of adults with complement 3 glomerulopathy (C3G), to reduce proteinuria.

     Recommended Vaccination and Prophylaxis for Encapsulated Bacterial Infections

Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis (serogroups A, C, W, Y and B), according to current ACIP recommendations at least 2 weeks prior to initiation of FABHALTA [see Warnings and Precautions (5.1)].

If urgent FABHALTA therapy is indicated in a patient who is not up to date with vaccines for Streptococcus pneumoniae and Neisseria meningitidis according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible [see Warnings and Precautions (5.1)].

Healthcare providers who prescribe FABHALTA must enroll in the FABHALTA REMS [see Warnings and Precautions (5.2)].

     Recommended Dosage

The recommended dosage of FABHALTA is 200 mg orally twice daily without regard to food.

Swallow capsules whole. Do not open, break, or chew capsules.

If a dose or doses are missed, advise the patient to take one dose of FABHALTA as soon as possible (even if it is soon before the next scheduled dose) and then to resume the regular dosing schedule.

     PNH Patients Switching From Anti-C5 (eculizumab, ravulizumab) to FABHALTA

To reduce the potential risk of hemolysis with abrupt discontinuation of other PNH therapies:

• For patients switching from eculizumab, initiate FABHALTA no later than 1 week after the last dose of eculizumab.
• For patients switching from ravulizumab, initiate FABHALTA no later than 6 weeks after the last dose of ravulizumab.

There is no available information regarding the timeframe for initiation of FABHALTA after other PNH therapies.

     Pregnancy

Risk Summary

Available data from clinical trials with FABHALTA use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH, IgAN, or C3G in pregnancy (see Clinical Considerations). The use of FABHALTA in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits.

In animal reproduction studies, oral administration of iptacopan to pregnant rats and rabbits during organogenesis at exposures 4- to 6-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 200 mg twice daily did not induce embryo or fetal toxicity (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombosis, infections, bleeding, miscarriages, increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery.

IgAN in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight.

C3G in pregnancy may be associated with adverse maternal outcomes, in particular preeclampsia and miscarriage, as well as adverse fetal outcomes including prematurity and low birth weight.

Data

Animal Data

In an embryo-fetal development study in rats, oral administration of iptacopan during organogenesis did not cause embryo-fetal toxicity when given up to the highest dose of 1,000 mg/kg/day, which corresponds to 4-times the MRHD based on AUC.

In an embryo-fetal development study in rabbits, oral administration of iptacopan during organogenesis did not cause embryo-fetal toxicity when given up to the highest dose of 450 mg/kg/day, which corresponds to 6-times the MRHD based on AUC.

In a pre- and postnatal development study in rats, oral administration of iptacopan during gestation, parturition, and lactation did not cause adverse effects in offspring when given up to the highest dose of 1,000 mg/kg/day, which corresponds to 4-times the MRHD based on AUC.

     Lactation

Risk Summary

There are no data on the presence of iptacopan or its metabolites in either human or animal milk, the effects on the breastfed child or on milk production. Since many medicinal products are secreted into human milk, and because of the potential for serious adverse reactions in a breastfed child, breastfeeding should be discontinued during treatment and for 5 days after the final dose.

     Pediatric Use

Safety and effectiveness in pediatric patients with PNH, IgAN, or C3G have not been established.

     Geriatric Use

There were 29 PNH patients 65 years of age and older in APPLY-PNH and APPOINT-PNH [see Clinical Studies (14)]. Of the total number of FABHALTA-treated patients during the 24-week treatment period in these studies, 21 (20.6%) were 65 years of age and older, while 7 (6.9%) were 75 years of age and older. There were 8 IgAN patients 65 years of age and older in APPLAUSE-IgAN [see Clinical Studies (14)]. Of the total number of FABHALTA-treated patients, 3 (2.4%) were 65 years of age and older. Clinical studies of FABHALTA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.

     Hepatic Impairment

The use of FABHALTA is not recommended in patients with severe hepatic impairment (Child-Pugh class C). No dose adjustment is required for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment [see Clinical Pharmacology (12.3)].