Biomarin Pharmaceutical Inc. has won FDA approval for Brineura (cerliponase alfa), the first therapy for children with the rare and fatal neurodegenerative condition ceroid lipofuscinosis type 2 (CLN2). The enzyme replacement therapy was approved to slow the loss of walking ability in symptomatic children, 3 years and older, with the late infantile form of the condition.

The new therapy will list for $702,000 per year, or $27,000 per carton — a price that Biomarin Chairman and CEO Jean-Jacques Bienaimé hinted on a call last week as being "at the high end for an ultra-rare indication." Patients will require a carton every other week.

Biomarin's chief commercial officer, Jeff Ajer, said the average annual cost of therapy is expected to be about $486,000 per patient after discounts associated with Medicaid or the 340B drug pricing program. The therapy is expected to be available in the U.S. by early June.

The FDA conducted a priority review for Brineura, which won breakthrough therapy and orphan drug status from the agency, though the approval arrived three months later than originally expected after the FDA requested an updated efficacy data cut from an extension study.

With Thursday's approval, San Rafael, Calif.-based Biomarin also secured a rare pediatric disease priority review voucher (PRV), the 10th voucher issued by the agency since the program's start and a valuable additional prize. Biomarin sold an earlier PRV it secured to Sanofi SA for $67.5 million. The company has not yet decided what to do with its latest voucher, Bienaimé said during a conference call held Thursday. (See BioWorld Today, Aug. 1, 2014.)

The approval follows a positive opinion from the EMA's Committee for Medicinal Products for Human Use, which on April 21 recommended approval for Brineura, which was reviewed under the EMA's accelerated assessment program. During last week's conference call Bienaimé said he saw "a very high likelihood" that the European Commission will support approval of Brineura later this quarter.

To potentially expand usage of Brineura to patients with CLN2 to younger children — a tiny group now, given that patients so young are rarely diagnosed — the FDA will require Biomarin to further evaluate the safety of Brineura in CLN2 patients below the age of 2, including device-related adverse events and complications with routine use. By contrast, European approval is expected to allow use of the therapy in patients of all ages, due to the potential benefits of the treatment.

A long-term safety study will be conducted to assess Brineura-treated CLN2 patients for a minimum of 10 years.

Initial revenues from the new therapy are expected to be modest as Biomarin works to ramp up awareness and early diagnosis of the disease, but Bienaimé estimated the therapy will be an important contributor toward the company's goal of 15 percent revenue growth through the end of the decade and will be essential to diversification of its portfolio.

CLN2, a pediatric brain disorder and a form of the rare lysosomal storage disorder Batten disease, is sometimes called Jansky-Bielschowsky disease. It's an autosomal recessive neurodegenerative disorder caused by mutations in the tripeptidyl-peptidase 1, or TPP1/CLN2, gene resulting in deficient activity of the enzyme tripeptidyl peptidase 1.

Biomarin estimates the incidence of CLN2 disease is about one in 200,000, with approximately 1,200 to 1,600 children in the company's commercial territories. In the U.S., about 20 children are born with CLN2 disease each year.

"Given the predictable and rapid course of CLN2, the commercial strategy of Brineura is more nuanced than previous Biomarin products, like Naglazyme or Vimizim for example," said Bienaimé. Rather than existing patient identification, the company's primary focus will be raising awareness of the disease to more physicians, both geneticists and pediatric neurologists, so as to facilitate early diagnosis, he said. "The goal is to have patients screened and diagnosed early while they retain a good level of function, as these will be the best candidates to benefit from Brineura."

Children with the disease are unable to produce enough TPP1 enzyme, which plays a role in breaking down certain proteins inside the cells. That causes the buildup of protein deposits in the cells, including nerve cells, which damage tissues and lead to progressive degeneration of the brain and retina. Most children with CLN2 lose their ability to walk and talk by the age of 6. Between the ages of 8 and 12, most die.

Cerliponase alfa is a recombinant human TPP1, designed to replace the missing enzyme, and is thereby expected to improve some of the symptoms experienced by the young patients. It is administered into the cerebrospinal fluid by infusion via a specific surgically implanted reservoir and catheter in the head, and a complete Brineura infusion, including the required infusion of intraventricular electrolytes, lasts about 4.5 hours.

Brineura's efficacy was established in a nonrandomized, single-arm, dose-escalation study in 22 children with CLN2, with data compared to 42 untreated patients with CLN2 disease from an independent historical control group who were at least 3 years old and had motor or language symptoms of the disease. Taking into account age, baseline walking ability and genotype, Brineura-treated patients demonstrated fewer declines in walking ability compared to untreated patients in the natural history cohort. (See BioWorld Today, March 4, 2016.)

The most common side effects in patients treated with Brineura have included fever, ECG abnormalities including slow heart rate, hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma, headache, irritability, increased CSF white blood cell count, device-related infection, feeling jittery and low blood pressure.

Shares of Biomarin (NASDAQ:BMRN) rose 19 cents to close at $96.26 on Thursday, the highest close for the company's shares year to date.

Biomarin licensed cerliponase alfa from the University of Medicine and Dentistry of New Jersey. Other teams working on CLN2 therapies include Spark Therapeutics Inc., which is developing SPK-TPP1, an investigational gene therapy for the condition, and Cornell University, which at last report was investigating a recombinant adeno-associated virus 10 vector-based gene therapy for CLN2 using Regenxbio Inc.'s NAV vector technology platform.