RegenXBio adds another CNS program to gene therapy plans

RegenXBio CEO Ken Mills (RegenXBio)

Fresh from its latest $175 million fundraising, gene therapy specialist RegenXBio has added another program to its pipeline, its third in neurodegenerative diseases.

The Maryland biotech says it is planning to start clinical trials in the U.S. and Europe next year of the new candidate, RGX-181, to treat late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease. CLN2 is one of the most common forms of Batten disease caused by mutations in the tripeptidyl peptidase 1 (TPP1) gene.

Last year, the FDA approved BioMarin Pharmaceutical’s TPP1 replacement therapy Brineura (cerliponase alfa) as the first specific treatment for neuronal ceroid lipofuscinosis disorders—with a princely price tag of around $486,000 per year.

A gene therapy approach offers the possibility of a one-shot therapy for the devastating disease, and RGX-181 aims to achieve this by using an adeno-associated virus (AAV) vector to deliver the TPP1 gene directly to the central nervous system in the hope that it can induce sustained levels of the TPP1 enzyme.

Batten disease is a fatal disease of the nervous system that typically begins in childhood, often between ages five and 10, and is linked to about 400 mutations across 13 different genes. It’s an autosomal recessive disease, meaning it generally occurs when both parents of a child are carriers of an abnormal gene, and affects fewer than one in 1 million children, roughly 22 a year, in the U.S.

The mutations disable the molecular systems for clearing waste from cells and lead to a catastrophic set of symptoms, including loss of speech, seizures, blindness, impaired mobility, and death—typically around the age of 12. CLN2 is a form of the disease that typically occurs in late infancy.

“CLN2 is a rapidly progressing, fatal disease with limited treatment options and no cure,” says Olivier Danos, Ph.D., RegenXBio’s chief scientific officer.

“Pharmacology studies conducted in an animal model of CLN2 disease demonstrated that a single administration of RGX-181 resulted in widespread distribution and sustained expression of the TPP1 enzyme in the CNS with significant improvements in neurobehavioral function and survival of the animals,” according to the company's statement.

RegenXBio now has three gene therapies for neurodegenerative diseases to go along with its RGX-314 candidate for wet age-related macular degeneration—which recently generated positive phase 1 results—and RGX-501 in phase 1/2 for homozygous familial hypercholesterolemia, a severe genetic disorder that causes elevated blood cholesterol and early-onset coronary artery disease.

The company's other neurodegenerative disease therapies, both in early-stage clinical development, are RGX-111 for mucopolysaccharidosis (MPS) type I and RGX-121 for MPS type II, both rare diseases caused by enzyme deficiencies. Meanwhile, licensees are also advancing gene therapies based on RegenXBio’s AAV platform, including Novartis, which is using one of its vectors for a spinal muscular atrophy type 1 gene therapy acquired as part of its $8.9 billion AveXis buyout earlier this year.

“As we prepare to initiate dosing in our clinical trials of RGX-111 for MPS I and RGX-121 for MPS II, adding RGX-181 to our research pipeline furthers our commitment to finding potential cures for children affected by these extremely serious and life-threatening neurodegenerative conditions,” says RegenXBio’s CEO Ken Mills.