FDA Approves New Treatment for Rare Disease
Cerliponase alfa (Brineura) is the first treatment approved to treat a form of Batten disease.
The FDA recently approved cerliponase alfa (Brineura) to treat a form of Batten disease. This makes cerliponase alfa the first and only approved drug to treat the loss of walking ability in children aged 3 and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) — also known as tripeptidyl peptidase-1 (TPP1) deficiency, according to a press release.
CLN2 belongs to a group of conditions called neuronal ceroid lipofuscinoses, which are referred to as Batten disease. CLN2 is a rare disease affecting the nervous system that typically presents between ages 2 and 4.
Patients with CLN2 may experience seizures, problems coordinating movements, muscle twitching, and vision loss. CLN2 also affects motor skills, including sitting and walking. Many patients require the use of a wheelchair and generally do not survive past their teens, according to the FDA.
Cerliponase alfa is an enzyme replacement therapy that is composed of a recombinant form of human TPP1, which is deficient in patients with the condition.
Cerliponase alfa is an infusion drug administered into the cerebrospinal fluid through a reservoir and catheter surgically implanted in the head. The FDA warns that the drug must be administered in sterile conditions to reduce the risk of infection. Cerliponase alfa should be managed by a healthcare provider who is familiar with the method of administration, according to the release.
The FDA has indicated cerliponase alfa is 300-mg for patients aged 3 and older administered every other week followed by an infusion of electrolytes. The treatment lasts approximately 4.5 hours. Approximately 30 to 60 minutes prior to treatment, the FDA recommends that patients be treated with antihistamines or corticosteroids.
The efficacy of cerliponase alfa was established in a clinical trial including 22 pediatric patients with CLN2 treated with the drug and 42 untreated patients with CLN2. After accounting for several factors, the investigators found that patients treated with cerliponase alfa had a smaller decline in walking ability compared with untreated patients, the FDA reported.
The safety of the drug was assessed among 24 patients with the condition aged 3 to 8. Common adverse events included fever, ECG abnormalities, hypersensitivity, decrease/increase in CSF protein, vomiting, seizures, hematoma, headache, irritability, increased CSF white blood cell count, device-related infection, jittery feeling, and low blood pressure, according to the release.
The FDA warns that patients should not receive treatment with cerliponase alfa if there are signs of device-related complications. If these complications are suspected, healthcare providers should stop infusion and refer to the manufacturing label. Additionally, cerliponase alfa should not be used in patients with ventriculoperitoneal shunts.
Healthcare providers should test CSF samples to detect infections. Providers should also monitor vital signs both during and after infusion. During the treatment, providers should use ECG monitoring for patients with a history of slow heart rate, conduction disorder, or structural heart disease, since some patients with CLN2 may develop conduction disorders or heart disease, according to the release.
Patients treated with cerliponase alfa have also reported anaphylaxis, so the FDA advises that appropriate treatment should be available during infusion. If anaphylaxis occurs, infusion should be stopped.
The FDA requires that the manufacturer evaluate the safety of cerliponase alfa in patients with CLN2 who are younger than age 2, in addition to a long-term safety study.
Cerliponase alfa was previously granted priority review and breakthrough therapy designation. It was also granted orphan drug designation.
“The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”