“The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options,” said director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, Dr Julie Beitz.
“Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”
Batten disease: A progressive, terminal illness
“Take your children home and enjoy the time you had left with them,” Tracy and Jennifer VanHoutan recalled doctors telling them. In 2009, the couple’s eldest son, Noah, was diagnosed with LINCL, a variation of Batten disease. A year later, their daughter Laine was also diagnosed with Batten disease, the CLN2 variant.
Batten disease is a rare genetic disease that causes patients to suffer from devastating and progressive neurological impairment such as seizures, visual impairment and loss of motor skills.
"Seizures start at approximately 3 to 4 years of age. And there is a combination of language delay and seizures and an abnormal EEG, a brain wave study,” explained Dr Emliy de las Reyes, the director of the Batten Disease Center of Excellence at Nationwide Children's Hospital in Ohio. “As the disease progresses, you lose the ability to walk and by about 5 or 6 years of age, they start to lose their vision."
The disease affects each patient differently due to widely varying genetic mutations, but is terminal and often results in early death of children, anywhere from the age of eight to 12 years.
Unhindered by their doctor’s advice, the VanHoutans decided to look at different avenues and founded Noah’s Hope. They worked closely with Batten Disease Support and Research Association (BDRSA) in an effort to raise funds for clinical research that could develop a potential cure or treatment for the debilitating disease.
These efforts eventually lead to the development of Brineura, said executive director of BDSRA, Margie Frazier.
"It's very important to note that these early funds were raised by parents who were very, very hopeful [while] knowing that their children were not going to benefit," Frazie said.
Enzyme replacement therapy to decelerate loss of ambulation
Brineura is an enzyme replacement therapy, which active ingredient, cerliponase alfa, is a recombinant form of TPP1, an enzyme that is deficient in patients with CLN2. In a non-randomized, single-arm dose escalation clinical study involving 22 symptomatic paediatric patients with CLN2 disease and 42 CLN2 patients who were untreated, patients treated with Brineura demonstrated fewer declines in their ability to ambulate.
The new FDA-approved drug is the first and only approved treatment for the disease, and works to decelerate the loss of ambulation specifically in paediatric patients with CLN2 who are aged three years and above. Though it treats only a specific form of Batten disease, Frazie has considered it a “milestone” for the community.
The VanHoutans, too, were elated with the drug’s approval – even though the treatment arrived too late for their children. Noah had passed away in 2016, a few weeks shy of his 12th birthday, while Laine, who is now 11 years old, has progressed too far to benefit from the new treatment.
“Seeing all of that come to fruition in an approved product last Thursday — it was rewarding, and it was bittersweet,” said the VanHoutans.
The safety and efficacy of Brineura has yet to be established in patients below the age of three, but the FDA will require the manufacturer to further evaluate its safety for patients of that age group. A long-term safety study will also monitor and assess CLN2 patients treated with Brineura for at least 10 years. MIMS
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