Spur Therapeutics’ Gaucher Disease Gene Therapy FLT201 Continues to Show Safety and Efficacy in Phase 1/2 Trial
Among the 5 patients in the efficacy set, 4 patients ceased receiving their previous standard of care therapy.
Spur Therapeutics’ (formerly known as Freeline Therapeutics) FLT201, an adeno-associated virus (AAV) vector-based gene therapy, has continued to show safety and efficacy in data from the phase 1/2 GALILEO-1 clinical trial (NCT05324943) evaluating the therapy for the treatment of Gaucher disease.1 The data were presented in a poster at the 21st Annual WORLDSymposium, held February 3 to 7, 2025, in San Diego, California.
The safety set included 6 adult patients treated with the trial’s low dose, 4.5x1011 vg/kg of FLT201, who had been followed for 9 to 17 months posttreatment. All 6 patients experienced at least 1 adverse drug reaction (ADR) while on-study. The most common ADRs deemed related to FLT201 itself included 7 cases of elevated alanine aminotransferase (ALT) reported in 6 patients, 4 cases of fatigue reported in 3 patients, 2 cases of activated partial thromboplastin time prolonged reported in 2 patients, and 2 cases of antiGCase neutralizing antibodies reported in 2 patients. It was noted that all ALT elevations, even those that did not exceed the normal range, were considered adverse events of special interest in GALILEO-1's protocol, and therefore were considered ADRs. Just 2 of the patients experienced ALT elevations above the normal range that were considered related to FLT201. Both of these patients’ cases resolved.
GALILEO-1 includes an immune management regimen that begins 3 weeks after patients are treated with FLT201. Among the 6 patients, 4 received a regimen of prednisone only and 2 received a regimen of prednisone and tacrolimus. The most common ADRs deemed related to prednisone included 3 cases of hyperglycemia in 3 patients, 2 cases of weight increase in 2 patients, and 2 cases of panic attack in 1 patient. The most common ADRs deemed related to tacrolimus included 4 cases of diarrhea in 4 patients.
It was additionally reported that transient antiGCase antibodies appeared in 2 patients, but that these did not affect safety or effect a loss of clinical benefit. Although, GCase expression decreased in these patients. One of these patients experienced a return to preantibody GCase levels after achieving antibody negativity.
“FLT201 is the result of our unwavering focus on developing gene therapies that change people’s lives,” Michael Parini, the CEO of Spur, said in a statement.2 “We purposefully designed FLT201 to overcome the shortcomings of currently approved therapies, engineering a more stable version of the GCase enzyme deficient in people with Gaucher disease and packaging it in a capsid that is highly efficient at transducing cells to produce the enzyme. We are seeing that work translate into benefits beyond what current therapies provide at a low dose that we believe could offer an important safety advantage over other gene therapies in development. We are moving quickly to initiate a Phase 3 study of FLT201.”
The efficacy set included 5 patients, with 1 of the aforementioned patients having been excluded. It was noted that a low antiAAVS3 titer was detected in the excluded patient at prior to treatment with the gene therapy, and that GCase expression has not been observed in this patient after treatment. The patient has continued to received standard of care (SOC) therapy.
Among the 5 patients in the efficacy set, 4 patients ceased receiving their previous SOC therapy, which was either enzyme replacement therapy or substrate reduction therapy, within 4 to 11 weeks of treatment with FLT201. At 38 weeks after treatment with FLT201, the 5 patients showed a mean dried blood spot glucosylsphingosine (DBS lyso-Gb1) level of 49.8 ng/mL (range, 12.0 to 172.0), compared to a baseline mean DBS lyso-Gb1 level of 185.8 ng/mL (range, 10.3 to 486.4). The poster authors additionally reported that levels of hemoglobin and platelets either improved or stayed within the normal range following treatment with the gene therapy. Although, they noted that 1 patients hemoglobin levels lowered because of an iron deficiency; the patient’s hemoglobin levels recovered to normal levels following treatment with iron supplementation. It was also reported that patients’ liver and spleen volumes either improved or were maintained following treatment with FLT201; notably, 1 patient’s spleen, which was enlarged prior to treatment, showed a reduction into the target goal volume by 38 weeks after treatment with FLT201.
“Gaucher disease is a debilitating chronic disorder, and despite treatment with currently approved therapies, many patients continue to have serious symptoms,” Pamela Foulds, MD, the chief medical officer of Spur, added to the statement.2 “Data from our phase 1/2 study being presented at the WORLDSymposium show that a single infusion of FLT201 led to improvements in persistent symptoms and disease involvement in patients who have been on approved therapies for years. These improvements, together with the favorable safety profile and durability of responses, highlight FLT201’s potential to provide better efficacy and dramatically reduce the treatment burden for people with Gaucher disease.”
A phase 3 clinical trial is planned for FLT201. Earlier this month, Spur announced that it had reached an accord with the FDA regarding plans for the design of the trial. The single-arm phase 3 trial, which the company expects will begin dosing patients in the second half of 2025, will evaluate decreases in lyso-Gb1 with the hope of supporting an accelerated approval for FLT201. The trial will also evaluate improvement or maintenance of hemoglobin levels, data from which may be used to support a full approval for the gene therapy. Platelet counts, and organ volume will constitute secondary end points for the trial, and bone health assessments and patient-reported outcomes will constitute exploratory end points.
