The FDA has approved cerliponase alfa to curb the loss of ambulation among patients aged 3 years and older diagnosed with late infantile neuronal ceroid lipofuscinosis type 2, an extremely rare and fatal autosomal recessive neurodegenerative disorder, also known as Batten disease.
One of a group of disorders known as neuronal ceroid lipofuscinoses, collectively referred to as Batten disease, ceroid lipofuscinosis type 2 (CLN2) primarily affects the nervous system, with initial symptoms including language delays, epilepsy and ataxia, as well as later symptoms of myoclonus and vision loss. In the late infantile form of the disease, signs and symptoms typically manifest between ages 2 and 4 years.
Children who inherit this condition often require the use of a wheelchair by late childhood and typically do not survive beyond their teenage years. Despite its severity, Batten disease is relatively rare, affecting less than one in one million U.S. residents, many of whom remain undiagnosed.
“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 of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, said in the FDA press release. “Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”
Intended to curtail the loss of walking ability in patients with CLN2, cerliponase alfa (Brineura, BioMarin) is an enzyme replacement therapy — a recombinant form of human tripeptidyl peptidase-1 — administered into the cerebrospinal fluid through infusion via an intraventricular access device.
According to the FDA, the recommended dose is 300 mg for patients aged 3 years and older, administered once every other week and followed by an infusion of electrolytes. Additionally, patients should be administered antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes before the start of the infusion, the FDA noted.
“We thank the FDA for recognizing Brineura’s potential to alter the course of CLN2 disease and its urgency in delivering this treatment to children as quickly and safely as possible. Brineura was approved in under 4 years from starting the first clinical trial to today, a significant achievement for a condition that progresses so rapidly,” Jean-Jacques Bienaimé, chairman and CEO of BioMarin, said in a release. “Treating children with CLN2 disease requires an extraordinary amount of collaboration between families, hospitals, advocates and physicians. We are grateful for the partnership of all those involved and look forward to continuing to work together to make Brineura accessible to children who may benefit.”
The FDA based its approval on safety and efficacy data assessed over 96 weeks in a non-randomized, single-arm dose escalation clinical study of 22 symptomatic patients with CLN2 disease vs. 42 untreated patients with CLN2 disease from a natural history cohort who were at least 3 years old and exhibited motor or language symptoms.
After considering age, baseline walking ability and genotype, the researchers noted that patients treated with cerliponase alfa exhibited fewer declines in walking ability compared with untreated patients in the natural history cohort. Although the safety of cerliponase alfa was examined in 24 patients with CLN2 disease aged 3 to 8 years who received at least one dose of cerliponase alfa, safety and effectiveness have not been established in patients younger than 3 years of age.
The most common adverse reactions among patients treated with cerliponase alfa included fever, ECG abnormalities including bradycardia, hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma, headache, irritability, pleocytosis, device-related infection and low blood pressure.
“The approval of Brineura is an extraordinary medical breakthrough for the CLN2 Batten community who have been waiting for this moment for more than a century when the condition was first described,” Margie Frazier, PhD, LISW-S, executive director of Batten Disease Support and Research Association, said in the release. “We appreciate BioMarin’s commitment and partnership to the CLN2 Batten community and investing the resources needed to bring this pivotal treatment to families.”