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General Information
Fabhalta (iptacopan) is a complement factor B inhibitor.
Fabhalta is specifically indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).
Dosing/Administration
Fabhalta is supplied as capsules for oral administration.
Prior to dosing:
- Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis (serogroups A, C, W, Y and B), and Haemophilus influenzae type B, according to current ACIP recommendations at least 2 weeks prior to initiation of Fabhalta.
- If urgent Fabhalta therapy is indicated in a patient who is not up to date with vaccines for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.
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.
Mechanism of Action
Fabhalta (iptacopan) binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway. In PNH, intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.
Side Effects
Adverse effects associated with the use of Fabhalta may include, but are not limited to, the following:
- headache
- nasopharyngitis
- diarrhea
- abdominal pain
- bacterial infection
- viral infection
- nausea
- rash
The Fabhalta drug label comes with the following Black Box Warning: FABHALTA increases the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B.
- Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of Fabhalta, unless the risks of delaying Fabhalta outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
- Patients receiving Fabhalta are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
- Fabhalta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Fabhalta REMS.
Clinical Trial Results
The FDA approval of Fabhalta was based on the Phase 3 APPLY-PNH trial in patients with residual anemia (hemoglobin < 10 g/dL) despite prior anti-C5 treatment who switched to Fabhalta. The trial demonstrated superiority in hemoglobin improvement in the absence of RBC transfusions and in transfusion avoidance rate over patients who stayed on anti-C5 treatments. Approval was also supported by the Phase 3 APPOINT-PNH study in complement inhibitor-naïve patients. The 24-week core treatment periods in APPLY-PNH and APPOINT-PNH trials respectively showed:
- Patients with sustained increase of hemoglobin levels ≥ 2 g/dLa from baseline in the absence of transfusions: 82.3% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 81.5%); 77.5% of complement inhibitor-naïve patients using Fabhalta achieved this outcome (sensitivity analysis showed 87.5%).
- Patients with sustained hemoglobin level ≥ 12 g/dLa in the absence of transfusions: 67.7% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 66.6%).
- Patients avoiding transfusion: Transfusion avoidance rate 95.2% for anti-C5-experienced Fabhalta patients vs. 45.7% for anti-C5 (difference of 49.5%).