Iptacopan (Fabhalta)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Fabhalta be reimbursed by public drug plans for adult patients with C3 glomerulopathy (C3G) to reduce proteinuria, if certain conditions are met.
• The Canadian Drug Expert Committee (CDEC) determined that it is uncertain whether Fabhalta demonstrates acceptable clinical value versus placebo in adult patients with C3G. Evidence from 1 clinical trial showed that Fabhalta reduced protein in the urine after 6 months of treatment, compared to placebo. The clinical impact of this reduction on patient health is uncertain. Fabhalta may decrease glomerular C3 deposit, which is associated with the pathologic mechanism of the disease. However, the evidence for Fabhalta is uncertain because the study was small and did not show whether the treatment improves kidney function or improves important long-term outcomes like kidney failure, heart problems, need for dialysis or kidney transplant, and survival.
• Due to the uncertainty in the evidence regarding Fabhalta, CDEC was unable to base its recommendation solely on clinical value. Therefore, the committee also considered whether Fabhalta addresses a significant unmet clinical need. C3G is a rare, serious kidney disease that leads to kidney failure in half of patients. Currently available therapies do not address the underlying disease and are mostly ineffective at stopping disease progression, and they often cause substantial side effects. Patients and caregivers report major impacts on daily functioning, emotional well-being, and financial stability. CDEC concluded that Fabhalta, a treatment option for adults with C3G that targets the underlying complement dysregulation, may address this unmet need to a degree that justifies a positive recommendation despite the uncertainty in the clinical value, considering the rarity and severity of the disease despite available treatments.
• There are significant unmet nonclinical needs and equity considerations due to the rarity of C3G. Patients face multiple types of treatment burdens, and this is especially the case for those who live far from specialized centres. Caregiver burdens include time away from work, income loss, and stress. Fabhalta is the first treatment for C3G that can be taken orally. CDEC concluded that this may reduce the burden of treatment and make it easier for patients, as it avoids the challenges that come with injections.
• Based on all of the preceding considerations, CDEC recommended that Fabhalta be reimbursed.
• Fabhalta should only be covered for patients aged 18 years or older with a confirmed diagnosis of C3G based on kidney biopsy, who have an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m² and a proteinuria level of at least 1 g/g. Fabhalta should not be used in patients with previous transplant other than kidney, nor in patients who have a rapidly progressive disease or severe chronic kidney injury (e.g., when most of the kidney tissue is scarred or damaged, based on a kidney biopsy); in these patients, it is unknown whether Fabhalta would show a similar level of benefit.
• Fabhalta should only be reimbursed if prescribed by a kidney specialist experienced in managing C3G, and if the cost of Fabhalta is reduced. Fabhalta should be initially covered for 6 months and may be continued if the patient shows a meaningful response (such as reduced protein in the urine with stable kidney function, or clear removal of C3 build-up in the kidneys, as seen on a follow-up kidney biopsy). Reassessment should be conducted at least every year.
• Important budget impact considerations must be addressed for health systems to be able to adopt Fabhalta.