Rare Disease Report

FDA Approves BioMarin's Batten Disease Drug. Cost Per Year is $702,000

APRIL 27, 2017
James Radke
UPDATE 04/28/2017
 Following the FDA approval of Brineura (cerliponase alfa), BioMarin announced the enzyme replacement therapy will cost $27,000 per biweekly infusion. That comes out to be a record breaking $702,000 a year to treat children with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2).

BioMarin noted that most patients who have CLN2 are on federal assistance programs such as Medicaid and the price after mandatory government discounts will be $486,000 for those patients.

Original Story posted 4/27/2017
The FDA has approved BioMarin’s Brineura (cerliponase alfa) to treat a form of Batten Disease.
More specifically, the orphan drug is approved to "slow loss of walking ability (ambulation) in symptomatic pediatric patients ages 3 years and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency."
The enzyme replacement therapy is a recombinant form of human TPP1, the enzyme deficient in CLN2 disease.
According to the FDA, the recommended dose of Brineura is 300 mg administered into the ventricles every 2 weeks. The procedure that takes about 4.5 hours. THE FDA recommends "pre-treatment of patients with antihistamines with or without antipyretics (drugs for prevention or treatment of fever) or corticosteroids is recommended 30 to 60 minutes prior to the start of the infusion."


The efficacy of Brineura was established in a clinical study involving 22 pediatric patients with CLN2 disease and the data was compared to 42 untreated patients with CLN2 disease from a natural history cohort.

Last fall, we reported on the data at 5th International Conference on Neuronal Ceroid Lipfuscinosis (Batten Disease) held in Boston, MA. During that meeting, Angela Schulz, MD, PhD, of the University Medical Center Hamburg-Eppendorf showed the latest data from the phase 1/2 open-label dose-escalation study and extension study examining the effects of cerliponase alfa in patients with CLN2 disease.
In the initial 48-week study, 24 children were enrolled with an average age of 4.3 years and an average CLN2 score of 3.6. Subjects were administered a stable dose of cerliponase alfa (300 mg by ICV infusion every 14 days) for at least 48 weeks.  After 48 weeks, all subjects were enrolled into an extension study which remains ongoing.
Of the 24, 23 completed the study. One withdrew from the study due to an extreme fear of needles that could not be overcome.
In the 48-week study, the primary endpoint (change in CLN2 score from baseline) was very encouraging.
Of the 23 patients:
·       13 patients showed no change in CLN2 score
·       2 patients showed an improvement of 1 point in the CLN2 score
·       5 patients showed a decrease of 1 point in the CLN2 score
·       3 patients showed a decrease of 2 points in the CLN2 score
In addition to the 48-week data, Dr. Schulz showed the most recent efficacy data in which the children have been receiving the drug for 81 weeks and overall, the data is even more impressive than at 48 weeks. After 81 weeks of treatment, the mean CLN2 score had remained stable. In contrast, data from a natural history cohort had a decrease of 3 CLN2 points over that time period. 


The most common adverse reactions in patients treated with Brineura include fever, ECG abnormalities including slow heart rate (bradycardia), hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma (abnormal collection of blood outside of a blood vessel), headache, irritability, increased CSF white blood cell count (pleocytosis), device-related infection, feeling jittery and low blood pressure.

Medical Professionals Needed to Monitor ERT Administration

The FDA noted some key points that medical professionals need to monitor for during treatment. These include:
  • Brineura should not be administered to patients if there are signs of acute intraventricular access device-related complications. In case of intraventricular access device complications, health care providers should discontinue infusion and refer to the device manufacturer’s labeling for further instructions.
  • Health care providers should routinely test patient CSF samples to detect device infections.
  • Brineura should also not be used in patients with ventriculoperitoneal shunts.
  • Health care providers should also monitor vital signs (blood pressure, heart rate, etc.) before the infusion starts, periodically during infusion and post-infusion in a health care setting.
  • Health care providers should perform electrocardiogram (ECG) monitoring during infusion in patients with a history of slow heart rate (bradycardia), conduction disorder (impaired progression of electrical impulses through the heart) or structural heart disease (defect or abnormality of the heart), as some patients with CLN2 disease can develop conduction disorders or heart disease.
  • Hypersensitivity reactions have also been reported in Brineura-treated patients. Due to the potential for anaphylaxis, appropriate medical support should be readily available when Brineura is administered. If anaphylaxis occurs, infusion should be immediately discontinued and appropriate treatment should be initiated.

More Studies Required

The FDA will require BioMarin to further evaluate the safety of Brineura in CLN2 patients below the age of 2 years, including device related adverse events and complications with routine use.
In addition, a long-term safety study will assess Brineura treated CLN2 patients for a minimum of 10 years. 

Priority Review Voucher

With the approval of the drug, BioMarin received a Rare Pediatric Disease Priority Review Voucher which they can use on ANY future drug or sell it to another company. In the past, these vouchers have sold for as high as $350 million but the prices have dropped a bit recently with Sarepta selling their’s for $125 million. Given that BioMarin is a rare disease company, they will likely sell their voucher to a company in need of beating the competition for a more common ailment.

Stay informed on the latest rare disease news and developments by signing up for our newsletter.
Copyright © RareDR 2013-2019 Rare Disease Communications. All Rights Reserved.