RARE Daily

Freeline Reports Positive Clinical Data from First Cohort of Phase 1/2 Gene Therapy Candidate for Gaucher Disease

October 4, 2023

Rare Daily Staff

Freeline Therapeutics reported positive initial safety, tolerability, and enzyme activity data from the ongoing phase 1/2 trial evaluating its experimental gene therapy candidate for the rare, lysosomal storage disorder Gaucher disease.

In addition to demonstrating a favorable safety and tolerability profile, data from the first two patients in GALILEO-1 show that a single infusion of FLT201 led to several hundred-fold increases in GCase activity in plasma and normalization of GCase activity in leukocytes.

Gaucher disease is caused by a mutation in the GBA1 gene that results in abnormally low levels of glucocerebrosidase (GCase), an enzyme needed to metabolize a certain type of lipid. As a result, harmful substrates glucosylceramide (Gb-1) and glucosylsphingosine (lyso-Gb1) build up in cells that then accumulate in various organs, causing inflammation and dysfunction. Gaucher disease is hereditary and presents in various subtypes.

Freeline is currently focused on Gaucher disease Type 1, the most common form of the disease, which affects the health of the spleen, liver, bone and lung. Despite treatment with existing therapies, many people with Gaucher disease continue to experience symptoms and disease progression. Gaucher disease affects approximately 18,000 people in the United States, United Kingdom, France, Germany, Spain, Italy, and Israel.

FLT201 is an adeno-associated virus gene therapy candidate that is designed to generate durable increases in glucocerebrosidase (GCase) and reduce the accumulation of harmful substrates, with the aim of providing a one-time treatment that can stop disease progression, improve outcomes, and free people from lifelong treatment. FLT201 uses Freeline’s proprietary AAVS3 capsid to introduce a novel transgene into liver cells to produce a rationally engineered GCase variant.

In preclinical studies, the GCase variant has demonstrated a greater than 20-fold increase in half-life at lysosomal pH conditions compared to wildtype human GCase. Preclinically, FLT201 has shown robust GCase expression, leading to significant GCase uptake and substrate reduction in key tissues.

“FLT201 is a highly differentiated gene therapy candidate for Gaucher disease with the opportunity to provide better outcomes for patients, while dramatically reducing the burden that comes with existing therapies,” said Pamela Foulds, Freeline’s chief medical officer. “The magnitude of the increases in plasma GCase activity in the first two patients treated with FLT201, together with the normalization of GCase activity in cells, further strengthens our belief in its therapeutic potential. Given the strong response and clean safety and tolerability to date, we have decided to treat a third patient at this dose rather than a higher dose as initially planned.”

Photo: Pamela Foulds, chief medical officer of Freeline Therapeutics

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