Long-term Data

Important Safety Information

CONTRAINDICATIONS

GENGLYCOS is contraindicated in patients with known severe hepatic fibrosis or cirrhosis.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

• Infusion-related reactions, including hypersensitivity reactions, occurred during GENGLYCOS administration.
• Premedicate with acetaminophen and non-sedating antihistamines and administer GENGLYCOS according to recommended infusion rates. Monitor patients during and after completion of GENGLYCOS infusion as clinically indicated. In the event of an infusion-related reaction, pause the infusion and provide supportive care as needed. If the infusion is paused, restart at half the prior rate after the infusion-related reaction has resolved.

Hepatic Reactions

• Predominantly mild to moderate, transient liver transaminase elevations were observed in clinical studies, most often in the first 15 weeks following GENGLYCOS administration.
• Prior to GENGLYCOS infusion, evaluate liver-related medical history and assess liver function by clinical examination and laboratory testing. Administer corticosteroids to all patients after GENGLYCOS infusion in order to mitigate hepatic reactions. Elevated transaminases may require adjustment of the corticosteroid treatment regimen, including increased dose or prolongation of the corticosteroid taper.
• Monitor transaminase levels for the first 6 months after GENGLYCOS administration. Continue to monitor transaminases in all patients who develop transaminase elevations, until transaminases return to baseline or as clinically indicated. If transaminase elevations are observed, consider all potential causes in the assessment of management for transaminase elevations, including infectious causes, alcohol, drugs, concomitant medication use, including herbal products and nutritional supplements, and worsening of underlying GSDIa, in addition to immune responses to GENGLYCOS.
• The effect of alcohol consumption on the magnitude and duration of the therapeutic effect has not been studied with GENGLYCOS treatment. Patients should be counseled on the potential risks of alcohol consumption following GENGLYCOS infusion.

Malignancy

• The integration of liver-targeting AAV vector DNA into the genome may carry the theoretical risk of tumorigenicity and may also insert into the DNA of other human body cells.
• GSDIa is associated with hepatic adenoma formation which carries a risk of transformation to hepatocellular carcinoma. Therefore, monitor patients with annual liver imaging, in particular patients with additional or other risk factors for hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age). In the event that a malignancy occurs, contact Ultragenyx Pharmaceutical Inc. at 1-888-756-8657.

Adverse Reactions

• The most frequent adverse reactions in clinical studies were transaminases increased (85%) and nausea (29%).

USE IN SPECIFIC POPULATIONS

Contraception

• Women of childbearing potential should use effective contraception for at least 48 weeks after administration of GENGLYCOS.
• For 6 months after administration of GENGLYCOS, men must not donate semen, and men of reproductive potential and their female partners must prevent or postpone pregnancy using an effective form of contraception.

PATIENT COUNSELING INFORMATION

Monitoring Nutritional Intake, Glycemic Control, and Metabolic Control

• Inform patients/caregivers of the importance of continued follow-up with their healthcare provider to monitor and adjust cornstarch and diet after receiving GENGLYCOS. At home, blood glucose should be monitored to avoid hypoglycemia and maintain normal blood glucose levels. Blood tests and dietary assessments may be needed to evaluate the appropriateness of nutritional modifications (cornstarch and diet) and to ensure glycemic and metabolic stability.

Vector Shedding

• As temporary vector shedding of GENGLYCOS occurs primarily via bodily waste, patients and caregivers should be instructed to follow appropriate hygiene precautions when handling patient waste for 3 months following GENGLYCOS infusion.

Report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Ultragenyx Pharmaceutical Inc. at 1-888-756-8657.

Please see the full Prescribing Information for GENGLYCOS.