Amicus Discontinues Gene Therapy Program for CLN6 Batten Disease

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Amicus Therapeutics announced it will discontinue its investigational gene therapy program of AT-GTX-501 for late infantile neuronal ceroid lipofuscinosis 6 disease, also known as CLN6 Batten disease.

The company is, however, advancing its gene therapy program for juvenile Batten disease, also known as CLN3 disease, according to a press release.

The decision to halt its CLN6 gene therapy program was based on data from a long-term follow-up study (NCT04273243) of CLN6 Batten patients, 1 year and older, that showed AT-GTX-501 failed to stabilize disease progression.

Patients were enrolled in the long-term follow-up (extension) study after completing a Phase 1/2 clinical trial (NCT02725580) where they received a one-time injection of AT-GTX-501 into the spinal canal (intrathecal).

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Interim data collected two years after injection showed that the gene therapy stabilized motor and language function.

Now, the company reports that the following extension study revealed that this stabilization effect was not sustained beyond the two years.

Amicus will conduct further analyses and plans to share the data with key stakeholders in the CLN6 community.

AT-GTX-501 delivers a working version of the CLN6 gene, which is mutated in people with the disease. That causes the toxic buildup of deposits called lipofuscins, especially in cells of the central nervous system (brain and spinal cord).

The gene therapy uses an adeno-associated virus (AAV), a common, naturally occurring virus, which was shown to work as an effective gene therapy delivery vehicle. The virus is modified in the lab to not cause disease.

Amicus has another gene therapy program for juvenile Batten disease. The company plans to advance the program, but with some tweaks, pending further data from the ongoing Phase 1/2 trial (NCT03770572) testing AT-GTX-502 in infants and children, ages 3–10, with juvenile Batten disease and new preclinical data. These data are expected this year.

In that trial, the therapy is administered by an injection directly into the patients’ spinal fluid (intrathecal injection), to ensure it reaches cells of the central nervous system. Early results showed that the gene therapy was well tolerated and has the potential to stabilize early signs of the disease in children and infants.

The new tweaks include using a higher dose, a different promoter (an element that acts like a switch to turn on genes), and a different route of administration — namely, directly in the brain into the cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord.

AT-GTX-502 uses an AAV, called AAV9, to deliver a functional copy of CLN3 — the gene that is faulty in CLN3 disease — to patients’ nerve cells. The therapy is expected to slow the physical and neurodevelopmental decline that characterizes the disease.

“We see further opportunity ahead to impact the lives of those living with rare disease through our genetic medicine business and capabilities,” John F. Crowley, chairman and CEO of Amicus, said. “Amicus is in a stronger position than ever and we remain steadfast on our mission of transforming the lives of people living with rare, life-threatening conditions.”