In April 2017, cerliponase alfa (Brineura™), developed by BioMarin Pharmaceutical, received its first global approval in the US to slow the loss of ambulation in symptomatic pediatric patients at least 3 years of age with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency, which is a specific and very rare form of Batten disease. Cerliponase alfa is a proenzyme form of a recombinant human (rh) TTP1 that is administered as an intracerebroventricular infusion via a surgically implanted catheter and reservoir. After administration the proenzyme is activated, subsequent to lysosome uptake, into a proteolytic form of rhTPP1 that cleaves proteins into tri-peptides from the N-terminus.
CLN2 is an ultra-rare form of disease with an estimated worldwide prevalence of approximately 0.7 per million and an incidence of 0.46 per 100,000 live births, according to one source. It has been reported in over 300 cases globally, and in the US the number is said to be growing by approximately 20 cases per year. The onset of the CLN2 form of Batten’s disease is commonly late infantile (2-4 years) and Juvenile (5-10 years) with respective life expectancies of approximately 10 and 20 years.
Cerliponase alfa is the first drug to be approved for use in patients with CLN2. Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin thanked the US FDA for its “urgency in delivering this treatment to children,” explaining that cerliponase alfa was approved within four years of initiating the first clinical trial, which he described as “a significant achievement for a condition that progresses so rapidly.”
The recognition for the need for speed was confirmed by Julie Beitz, M.D., director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research when she stated that, “The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options … Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”
Cerliponase alfa has been granted Orphan Drug and Breakthrough Therapy designations and was approved via the Priority Review pathway; additionally BioMarin Pharmaceuticals was given a Rare Pediatric Disease Priority Review Voucher by the FDA.
In late May, cerliponase alfa was also approved in Europe for the same indication in children from birth.
Prescribing information warnings and precautions primarily relate to complications associated with the intraventricular access device, cardiovascular and hypersensitivity reactions. The FDA requires Biomarin Pharmaceuticals to further evaluate the safety of cerliponase alfa, including the delivery device, in children under 2 years, and separately assess long-term safety for a minimum of 10 years.
For further information related to the first approval of cerliponase alfa please visit Drugs or to learn more about the overall development of cerliponase alfa across all indications visit AdisInsight.