Pegzilarginase (Loargys)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Loargys be reimbursed by public drug plans for the treatment of hyperargininemia in adults and pediatric patients aged 2 years or older with arginase 1 deficiency (ARG1-D), in conjunction with dietary protein restriction, if certain conditions are met.
• The Canadian Drug Expert Committee (CDEC) determined that it is uncertain whether Loargys demonstrates acceptable clinical value compared with placebo plus individualized disease management in adults and pediatric patients aged 2 years or older with ARG1-D, in conjunction with dietary protein restriction.
• Evidence from 1 clinical trial showed that 24 weeks of treatment with Loargys resulted in a clinically meaningful reduction in plasma arginine levels compared with placebo in adults and pediatric patients aged 2 years or older with ARG1-D who were receiving stable, individualized disease management. Although there is uncertainty in whether arginine reduction translates into improved clinical outcomes, CDEC indicated that arginine levels may be an acceptable measure of treatment benefit, given the potential challenges with evidence generation in rare diseases. The trial also suggested that Loargys likely results in a clinically important improvement in health-related quality of life (HRQoL) but may result in little to no difference in clinical outcomes, including neurologic, motor, and cognitive functioning, as well as adaptive behaviour, when compared with placebo. Results from the long-term extension phase of the trial suggested potential benefits in clinical outcomes over time with Loargys treatment; however, the evidence is uncertain because the extension study did not include a comparison group.
• CDEC established that there was a significant unmet clinical need due to the rarity and severity of hyperargininemia. Patients and caregivers highlighted a significant need for disease-modifying therapies that prevent neurologic deterioration; stabilize or improve mobility, cognitive function, and overall daily functioning; reduce symptoms; and lessen reliance on restrictive dietary management. CDEC concluded that treatment with Loargys may address a significant unmet clinical need with an acceptable level of certainty in the clinical value.
• Based on the preceding considerations, CDEC recommended that Loargys be reimbursed.
• Loargys should only be covered for adult and pediatric patients aged 2 years or older with a confirmed diagnosis of ARG1-D and plasma arginine levels of 250 µmol/L or above.
• Loargys should only be reimbursed if it is prescribed by a specialist with experience managing ARG1-D or managing patients with inherited metabolic diseases, and if the cost of Loargys is reduced. The duration of initial authorization is 24 weeks. For the first renewal after initial authorization, the physician must provide proof of clinical response, defined as a reduction of plasma arginine concentrations within the normal range. Subsequent renewals may be conducted every 12 months, and the clinical response achieved after the initial authorization must be maintained as assessed by the treating physician.