The American Society of Gene and Cell Therapy (ASGCT) held its 27th Annual Meeting from May 7-11, 2024. During the conference, stakeholders in the field of cell therapy come together to discuss the latest scientific research and novel technologies. Biospace shares that this year, clinical-stage biotechnology company Freeline Therapeutics presented clinical data from the ongoing Phase 1/2 GALILEO-1 study. This study is evaluating a gene therapy candidate called FLT201 for Gaucher disease, a rare lysosomal storage disorder.

What is Gaucher Disease?

As described above, Gaucher disease is a rare lysosomal storage disorder and inherited metabolic disorder characterized by low or non-existent beta-glucocerebrosidase. Normally, this enzyme breaks down lipids like glucocerebroside into glucose and ceramide. In Gaucher disease, GBA mutations mean the body does not have enough beta-glucocerebrosidase. Glucocerebroside then begin building up in the body, especially in the bone marrow, liver, and spleen, leading to organ and tissue damage. Gaucher disease can happen in people of all backgrounds but is significantly more common in those of Ashkenazi Jewish descent.

This condition is broken down into multiple subtypes, including a perinatal lethal form. Gaucher disease type I ranges from mild-to-severe. Symptoms may include anemia (low red blood cells), easy bruising, chronic fatigue, thrombocytopenia (low platelet count), an enlarged liver or spleen, lung disease, and bone pain, fracturing, or arthritis. Treatments for Gaucher disease types I and III include enzyme replacement therapies like VPRIV, Elelyso, and Cerezyme, as well as medications like Cerdelga and Zavesca.

In type II, symptoms can include the same symptoms as above, as well as hypotonia (low muscle tone), failure to thrive, strabismus (crossed eyes), muscle spasticity, difficulty feeding, skin abnormalities, seizures, brain damage, and unusual eye movement. This form is typically life-threatening. Many infants with Gaucher disease type II do not survive infancy. There are no available treatments for this subtype.

Gaucher disease type III includes discussed blood and bone abnormalities, as well as ataxia, neurological deterioration, horizontal gaze palsy, and myoclonic seizures. It is also life-threatening but progresses more slowly than type II.

ASGCT Presentations

In the late-breaking presentation on the GALILEO-1 study, researchers discussed the impact of FLT201 on adults with Gaucher disease type I. FLT201 is a gene therapy delivered using adeno-associated viral vectors. It works by delivering, and prompting the body to produce, enough beta-glucocerebrosidase. This one-time treatment could help the body to clear harmful buildup from tissues and organs. Preclinical studies have shown that FLT201 improves beta-glucocerebrosidase expression. Data presented at the conference, based on four adults treated in the GALILEO-1 study, shows that:

• FLT201 improves and maintains hemoglobin levels. The treatment also reduced bone marrow burden and cleared toxic byproducts from the bone marrow.
• When using FLT201, one patient showed significant improvements in fatigue and daily function.
• Beta-glucocerebrosidase levels rose and were sustained in the body following gene therapy administration.
• FLT201 was safe and well-tolerated. While some individuals saw mild ALT elevations, the drug had relatively few side effects.

Outside of the presentation, FLT201 was also granted Priority Medicines designation in Europe and Regenerative Medicine Advanced Therapy designation in the United States.