RGX-181 gene therapy seen to reduce child’s seizures by over 80%

No serious side effects for 5-year-old with late infantile Batten disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A child with late infantile Batten disease treated with the gene therapy RGX-181 experienced a more than 80% reduction in seizure frequency over the following six months, without any serious side effects.

That’s according to data from a single-patient study that were announced by RGX-181’s developer, Regenxbio, in a letter to the Batten community.

In this first-in-human, investigator-initiated trial, a 5-year-old child was given a single dose of the experimental gene therapy, the letter stated.

“We are encouraged by the initial results demonstrating that RGX-181 is well tolerated and dramatically reduced the number of seizures in the patient enrolled in this trial,” Steve Pakola, MD, Regenxbio’s chief medical officer, said in a company press release.

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Early data support Regenxbio’s gene therapy program for CLN2 disease

Late infantile Batten disease patient shows fine motor skill gains

Late infantile Batten disease, also called neuronal ceroid lipofuscinosis type 2 (CLN2) disease, is caused by mutations in the gene that provides instructions for making the protein TPP1.

This protein is needed to break down certain types of cellular waste. Without a working version, molecular debris builds up to toxic levels inside cells, especially nerve cells, causing damage that leads to disease symptoms.

The current standard of care for CLN2 disease is enzyme replacement therapy (ERT), in which a version of the TPP1 protein is administered into the brain. While such therapy can ease or eliminate symptoms, it only works temporarily — without lifelong administration of the enzyme, disease symptoms will return.

Gene therapy, on the other hand, is needed just once.

RGX-181 is designed to deliver a healthy copy of the gene encoding TPP1 to cells in the brain, allowing them to make a functional version of this protein to clear the toxic molecular waste. The therapy delivers its genetic payload using an engineered virus, specifically an adeno-associated virus serotype 9 (AAV9). This type of virus is commonly used in gene therapies because it’s easy to genetically manipulate and doesn’t cause serious illness in people.

Researchers at Hospital de Clinicas in Porto Alegre, in Brazil, had launched this clinical trial, in which a single child with CLN2 disease was treated with RGX-181. The therapy was delivered into the brain via a one-time procedure.

Six-month data, collected as of June, show that the gene therapy treatment was overall well-tolerated, with no serious side effects reported. Biomarker data suggest an increase in TPP1 protein levels as designed.

The treatment also led to a substantial decrease in the child’s seizure frequency, by 86%, allowing the youngster to stop taking two anti-seizure medications. The child is still receiving ERT, but the beneficial effects of gene therapy have allowed such infusions to be given less frequently.

Researchers also observed “encouraging improvements in fine motor and expressive language skills,” according to Regenxbio.

The remarkable decrease in seizures, encouraging safety results and reduction in ERT frequency [in this patient] highlight the potential of this gene therapy to provide a meaningful treatment option to the CLN2 patient community

“As someone who treats patients with this devastating disease, I see the limitations of the current standard of care,” said Carolina Fischinger de Souza, MD, PhD, an investigator on the trial at the hospital.

“The remarkable decrease in seizures, encouraging safety results and reduction in ERT frequency highlight the potential of this gene therapy to provide a meaningful treatment option to the CLN2 patient community,” Fischinger said.

Regenxbio also is developing another gene therapy for CLN2 disease, called RGX-381, which is designed to be administered into the eyeballs to address blindness. The first participant in a clinical trial testing RGX-381 was recently dosed.

The U.S. Food and Drug Administration has both granted RGX-181 and RGX-381 orphan drug and rare pediatric disease designations, which are designed to speed and incentivize the development of treatments for rare diseases.