Freeline touts biomarker, clinical wins for FLT201 Gaucher gene therapy
09 May 2024
Clinical ResultGene TherapyASH
Roughly a year after Freeline Therapeutics halted work on its Fabry disease programme and axed nearly a third of its staff, the company provided evidence that its other experimental gene therapy could mark a significant advance in patients with Gaucher disease. On Thursday, it reported that FLT201 led to substantial reductions in a key biomarker predictive of positive outcomes as well as early signs of clinical benefit.
Ozlem Goker-Alpan, an investigator on the Phase I/II GALILEO-1 trial, said "a gene therapy that could deliver the same or better efficacy than currently available treatments, while freeing people from an ongoing treatment burden, would mark a significant advance in the treatment paradigm."
Freeline reported positive results from the study's first participant last October. The new data, unveiled at the American Society of Gene and Cell Therapy (ASGCT) annual meeting, are derived from the first four patients treated in the study. FLT201 consists of an adeno-associated virus vector designed to deliver a longer-lasting glucocerebrosidase (GCase) enzyme to clear harmful buildup of lipid substrates in cells and organs throughout the body, including hard-to-reach tissue such as bone.
Early efficacy signals
Freeline said the patients, who received a single intravenous dose of 4 of 4.5x1011 vg/kg, achieved "robust and continuous" GCase expression after infusion. Those who entered the study with persistently high levels of glucosylsphingosine (lyso-Gb1), despite years of treatment with standard enzyme replacement (ERT) or substrate reduction therapies (SRT), saw "substantial reductions" in this key Gaucher biomarker highly correlated with clinical response.
Moreover, in addition to maintaining haemoglobin and platelet levels post-withdrawal of ERT or SRT, the data also showed reductions in bone marrow burden, indicating substrate clearance from this difficult-to-treat area afflicted in Gaucher and reappearance of healthy fatty marrow. One patient also experienced "clinically meaningful" improvement in fatigue levels – scoring a 21-point gain on the FACIT fatigue scale that translated into improved daily functioning and abilities.
Safetywise, there were no infusion reactions or serious adverse events. The company said "modest" ALT increases in some patients were managed with immune therapy, with no impact to efficacy.
During ASGCT, Freeline also shared promising preclinical data supporting its strategy of extending the therapeutic potential of its GCase85 enzyme into a genetically linked subset of Parkinson's disease patients with GBA1 mutations. It said early research demonstrates "an order of magnitude higher" GCase activity with GCase85 compared to wildtype enzyme, in both in vitro and in vivo models, as well as stronger expression and broader GCase distribution in the brain than a wildtype AAV9-GBA1 construct when directly injected into the brain in mice.
The company has been trying to bounce back from a challenging 2023, which saw it drop its Fabry disease programme FLT190 in order to concentrate on its Gaucher disease candidate, and lay off 30% of its workforce. Majority shareholder Syncona later stepped in by offering to take the struggling biotech private, a move that Freeline shareholders approved this past February.
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