The US Food and Drug Administration (FDA) has approved cerliponase alfa (Brineura, BioMarin International Ltd) to treat symptomatic children aged 3 years and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a form of Batten disease.
CLN2 is a rare fatal lysosomal storage disorder characterized by a deficiency in enzyme tripeptidyl peptidase-1 (TPP1), which leads to a build-up of protein deposits in the cells, including nerve cells. This damages tissues and leads to progressive degeneration of the brain and retina. Most children with CLN2 lose their ability to walk and talk by the age of 6 years. Often children with CLN2 die between 8 and 12 years of age.
Cerliponase alfa is a recombinant form of TPP1 that replaces the missing enzyme.
Cerliponase alfa had orphan drug and breakthrough therapy designations and received priority review. It's the first drug approved by the FDA to slow loss of walking ability in children with CLN2.
"The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options," Julie Beitz, MD, director, Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research, said in a statement. "Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition."
Cerliponase alfa is administered into the cerebrospinal fluid (CSF) by infusion via an intraventricular access device. The recommended dose is 300 mg given once every other week, followed by an infusion of electrolytes. The complete treatment takes approximately 4.5 hours. Patients should receive antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes before the start of the infusion, the FDA said.
The efficacy of cerliponase alfa was demonstrated in a nonrandomized, single-arm dose-escalation clinical study involving 22 symptomatic children with CLN2 disease and 42 untreated children with CLN2 disease from a natural history cohort.
After taking into account age, baseline walking ability, and genotype, patients treated with cerliponase alfa had fewer declines in walking ability compared with untreated patients, the FDA said.
The most common adverse reactions in patients treated with cerliponase alfa include fever, electrocardiogram (ECG) abnormalities (including bradycardia), hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma, headache, irritability, pleocytosis, device-related infection, feeling jittery, and low blood pressure.
Cerliponase alfa should not be administered if there are signs of acute intraventricular access device–related complications, such as leakage, device failure, or signs of device-related infection (eg, swelling, erythema of the scalp, extravasation of fluid, or bulging of the scalp around or above the intraventricular access device).
If intraventricular access device complications do occur, clinicians should discontinue cerliponase alfa infusion and refer to the device manufacturer's labeling for further instructions, the FDA said.
Clinicians should also routinely test CSF samples to detect device infections. Cerliponase alfa should not be used in patients with ventriculoperitoneal shunts.
In addition, clinicians should monitor vital signs before the infusion starts, periodically during infusion, and after infusion, and they should perform ECG monitoring during infusion in patients with a history of bradycardia, conduction disorder, or structural heart disease, the FDA said.
Hypersensitivity reactions have been reported in cerliponase alfa–treated patients. Because of the potential for anaphylaxis, appropriate medical support should be readily available when the drug is administered. If anaphylaxis occurs, infusion should be immediately discontinued and appropriate treatment should be initiated, the FDA said.
The FDA will require the manufacturer to further evaluate the safety of cerliponase alfa in patients with CLN2 younger than age 2 years. In addition, a long-term safety study will assess cerliponase alfa–treated patients for a minimum of 10 years.
Earlier this month, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of cerliponase alfa for CLN2 disease.
Cite this: FDA Clears Cerliponase Alfa (Brineura) for Form of Batten Disease - Medscape - Apr 27, 2017.