CHMP Backs Two Orphan Drugs for Neurodegenerative Disorders

Megan Brooks


April 21, 2017

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval for two orphan drugs given accelerated review that is designed to facilitate access to medicines meeting an unmet medical need.

At its April meeting, CHMP recommended approval for cerliponase alfa (Brineura, BioMarin International Ltd) for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare, fatal neurodegenerative disorder in children.

At this meeting, the CHMP also recommended approval of nusinersen (Spinraza, Biogen Idec Ltd) for spinal muscular atrophy (SMA). This drug was approved for the treatment of SMA on December 23, 2016, by the US Food and Drug Administration.

Cerliponase Alfa for CLN2

CLN2 is a lysosomal storage disorder characterized by a deficiency in enzyme tripeptidyl peptidase 1 (TPP1), which leads to a build-up of protein deposits in the cells, including nerve cells. This damages tissues and leads to progressive degeneration of the brain and retina. Most children with CLN2 lose their ability to walk and talk by the age of 6 years. Often children with CLN2 die between 8 and 12 years of age.

Cerliponase alfa is a recombinant form of TPP1 that replaces the missing enzyme.

The safety and efficacy of this agent were assessed in a single-arm, open-label phase 1/2 study involving 24 children 3 to 8 years old.

"In the study, 20 of the 23 patients treated (and who could take part in the efficacy analyses) experienced either a slower than expected progression of the disease, a stabilization of the progression of the disease or some improvement in their motor and language abilities. This was considered a significant therapeutic effect," the EMA said in a news release.  

In an extension study, the slowdown in the progression of the disease was observed for more than 1 year and occurred even when the disease was already advanced.

The most common side effects were fever, vomiting, hypersensitivity, seizures, and upper respiratory tract infections.

The CHMP has asked the company to complete an ongoing study of cerliponase alfa that is part of the pediatric investigation plan to further assess its safety, efficacy, and tolerability, with a particular focus on children younger than age 2 years. The company will also monitor the long-term safety of the medicine through a patient registry.

The product will be available as a solution for intracerebroventricular infusion (150 mg) and should  be administered only by a trained healthcare professional knowledgeable in intracerebroventricular administration, the EMA said.

Nusinersen for SMA

The CHMP also recommended approval of nusinersen for treatment of 5q SMA, a rare autosomal-recessive disorder characterized by progressive weakness of motor neurons that typically begins between 6 and 12 months of age.

The product is an antisense oligonucleotide that makes the SMN2 gene produce adequate levels of full-length SMN protein, thus improving neuronal survival, the EMA said in a news release.

"The benefits with Spinraza are its ability to allow achievement of motor milestones and improvement in muscle function which is not observed during the natural course of the disease. The most common side effects are related to its administration via lumbar puncture," the EMA said.

Recommendation for approval was based on the CHMP's assessment of two pivotal controlled studies, ENDEAR in infantile-onset SMA and CHERISH, a trial including patients with later-onset SMA, "which both demonstrated the clinically meaningful efficacy and favorable safety profile," Biogen reported in a news release.

The drug will be available as a 2.4-mg/mL solution for injection and should be initiated only by a physician with experience in the management of SMA, the EMA said.

Detailed recommendations for the use of cerliponase alfa and nusinersen will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the European Commission grants marketing authorization.

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