Although Brineura (cerliponase alfa) is now approved both in Europe and the U.S. to treat CLN2 type Batten disease, its clinical trial path is far from over.
As the approval rested on a small Phase 1/2 trial, an ongoing extension study (NCT02485899) is gathering additional safety and efficacy data. Meanwhile, the U.S. Food and Drug Administration (FDA) has requested a new study in children under the age of two.
The discussions that followed Brineura’s U.S. approval, however, did not focus so much on its safety profile or effectiveness in slowing disease progression. Rather, it was its hefty price tag that drew attention. Brineura’s developer BioMarin has set a list price of $27,000 for each biweekly infusion, or about $702,000 a year, landing the company in the midst of ongoing criticism of exaggerated drug prices.
According to Bloomberg, the price — that may end up at $486,000 a year after mandatory government discounts for those on Medicaid — is among the highest drug prices in the world.
BioMarin reported $304 million in revenues for the first quarter of 2017 — a 28 percent increase compared to the same period in 2016. The June introduction of Brineura on the U.S. market is likely to further boost the company which, despite high revenues, did not report substantial profits. In fact, BioMarin reported a GAAP (generally accepted accounting principles) net loss of $16 million, a marked improvement over the GAAP net loss of $83 million reported for the first quarter of 2016.
“The recent FDA approval and positive CHMP opinion of Brineura marks a significant regulatory accomplishment for the Company and more importantly, a turning point for families living with CLN2 disease who now have an approved treatment option,” BioMarin’s CEO and Chairman Jean-Jacques Bienaimé said in the report.
“The speed with which global health authorities reviewed our applications both in the U.S. and Europe speaks to the value our innovative medicines provide patients,” he added.
A new drug for a devastating disease
Brineura is the only approved treatment for CLN2, or late infantile neuronal ceroid lipofuscinosis type 2. The disease, which typically leads to the death of affected children by their teenage years, ravages the brain.
The method of drug administration is a sign of the severity of the condition. Brineura is given as an infusion into the fluid bathing the brain and spinal cord. This is accomplished with the help of a catheter surgically implanted in the head.
Because of the high risk of infections — not to mention the devastating effects of getting foreign microbes into the brain — the drug is given under sterile conditions.
The infusion, given every two weeks, replenishes a patient’s defective TPP1 enzyme — the cause of the disease.
Former, current, and future trials
Given the severity of the condition and the lack of treatment options, the U.S. Food and Drug Administration (FDA) approved Brineura based on data of a yearlong Phase 1/2 trial (NCT01907087) in 24 children with CLN2 disease.
The study did not include a control group. The impact of treatment was, instead, assessed by comparing trial participants’ decline to that of children going through to the natural course of the disease — observed in earlier studies.
But 23 of the 24 children were recruited into a long-term trial that continues gathering data on the safety and effectiveness of the treatment. The study will gather data through December 2021 and will also reveal how the treatment impact specific developmental milestones among the children, and how it impacts their quality of life.
In addition, the FDA requested another trial to be made. CLN2 symptoms typically emerge when children are between two and four years old. But the original trial included only children aged three and above. BioMarin, therefore, needs to gather data of the drug’s safety and efficacy also in children younger than two.
A Phase 2 clinical trial (NCT02678689), that plans to recruit 10 patients aged 17 and below is ongoing, but it is not clear whether BioMarin will launch another trial that focuses exclusively on children below the age of two.
The June 1 approval of Brineura by the European Commision was a signal to the Batten community that regulatory authorities indeed considered their unmet medical need an urgent one. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval of the drug on April 21.
The approval was met by enthusiasm among researchers involved in the studies.
“Today represents several important milestones for the medical and patient communities, and also for me, both professionally and personally,” Angela Schulz, with Children’s Hospital at the University Medical Center Hamburg-Eppendorf and principal investigator of the Brineura studies, said in a press release.
“For the first time since entering this field nearly 15 years ago, I can now tell families affected by CLN2 disease that there is a meaningful treatment that may help their child, and provide hope,” she added.
In the release, Bienaimé spoke about the company’s efforts to launch a molecular diagnostics aid to enable earlier diagnosis of the disease, which is often misdiagnosed as epilepsy.
“With a treatment now available, accelerating early diagnosis will be critical,” said Bienaimé.