Assessing Spur Therapeutics’ Gene Therapy FLT201 in Gaucher Disease

Reena Sharma, MD
Credit: Northern Care Alliance NHS Foundation

Spur Therapeutics' FLT201, an adeno-associated virus (AAV) vector-based gene therapy, is currently being evaluated for the treatment of Gaucher disease in the phase 1/2 GALILEO-1 clinical trial (NCT05324943).¹ Results from this study were recently presented by Reena Sharma, MD, an adult metabolic consultant at Salford Royal Hospital, at the 21st Annual WORLDSymposium, held February 3 to 7, 2025, in San Diego, California.²

CGTLive® interviewed Sharma about her presentation during the conference. She explained the design of the gene therapy product and discussed the main findings of the study and their implications.

CGTLive: Can you give some background context about your presentation?

Reena Sharma, MD: What we really presented is about Gaucher disease type 1. People in the healthcare sector do know what Gaucher disease is, it is actually one of the most common lysosomal storage disorders and the first disease where there was a licensed enzyme replacement therapy (ERT). In the current standard of care for these patients, there are choices of ERT and substrate reduction therapy (SRT), as well. These therapies have addressed quite some of the significant health issues with this cohort of patients, but we do know that there are still unmet needs and there is a possibility of exploring something different and something new for this group of patients. That is a kind of a background for Gaucher disease, and what we really looked at in this clinical trial is an adult cohort of Gaucher patients and tried this unique gene therapy to see what was the response to the therapy.

Can you give an overview of the key results that were presented?

As I said, it's an adult clinical trial, and we recruited 6 patients with Gaucher disease type 1 who had disease diagnosed at the age of 3 or 4, and had a duration of standard of care therapy varying from 4 to 24 years. These patients had been on a very stable dose of ERT or SRT for up to 2 years before they were recruited. There were male and female patients and all the patients had their antibodies checked for AAVS3 vector, which is the capsid used in the gene therapy. They also had their baseline measurements for all their current disease burden, in terms of their glucosylsphingosine (lyso-Gb1), their scans, their hemoglobin, their platelet—that was like baseline characterization of all these patients.

Once that was done and once we were satisfied that they met the inclusion criteria, all these patients received this unique product, which is an AAVS3 vector carrying a transgene. Once they received this therapy, they were monitored closely over a significant period, and to date it is about 17 months at the time of data cut-off that they have been monitored and carefully evaluated.

I think before we talk about the results, I think it's important to understand what the product is. FLT201 is the investigational medicinal product, and the product has a capsid of AAVS3. This capsid has got human liver-tropic properties allowing it to take up in the tissues much more easily and more effectively. This capsid carries the transgene GBA85 and this transgene encodes a variant enzyme called GCase85. This variant enzyme is slightly different to the wild type or human GCase by about 2 amino acids. As a result of this variation, it has got very high affinity, stability, and availability in the human blood by about 6 times and the availability in lysosomes at low pH is about 20 times. These were the characteristics of this unique gene therapy. Patients received a single dose of 4.5x10¹¹ vg per kilogram of body weight and as per protocol, from Week 3, they had immunosuppressant therapy, including prednisolone and tacrolimus.

What we really saw in this cohort of patients is a very good response to the rise in the GCases85. Not only that, we also showed a good response to the key clinical markers, or biochemical markers, in this cohort of patients. Within the first 4 weeks of having this therapy, you can see that there was a significant decline in the lyso-Gb1, which is one of the key biochemical markers in this cohort of patients, and that remains steady throughout the follow-up period, till the data cut-off. Not just that, the patients' hemoglobin and platelets also remained stable. Four patients stopped their standard of care therapy within 4 to 11 weeks. What is important to understand is, in spite of stopping their ERT or SRT, they still managed to maintain their lyso-Gb1, as well as hemoglobin and platelet. This is what we really saw in this cohort of patients.

One patient, who had a very small amount of positivity for capsid antibodies, did not show any response or expression of GCase85, so that patient's data has not not been included in the overall efficacy data, but it has been included in the safety data.

In summary, we have got these 5 patients who have got expression of GCase and are showing stability of that, and 4 of these patients have come off their standard of care therapy, which is either ERT or SRT, and have maintained their low lyso-Gb1, as well as normal hemoglobin and platelets, up to 14 months since the stop of their standard of care therapy.

What would you say are the big picture implications of these findings?

I think these results are very promising. If I had to summarize it to my clinical community, I would say the unique characteristics of FLT201, in terms of its liver-specific properties, as well as the variant enzyme GCase85, have shown a good stability, availability, and efficacy in this small cohort of patients and the data looks very promising. There is certainly promise that this product should be investigated further in a bigger trial to explore the efficacy and long-term benefits of this product. It certainly offers a very promising result and makes a case for exploring further as a treatment for this group of patients in the future, which can not only stabilize the condition, but also actually take away some of the disease burden that has not been managed by the current therapy.

This transcript has been edited for clarity.

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REFERENCES
1. Sharma R, Goker-Alpan O, Schwartz I, Giraldo P, Ferrante F, Foulds P. Results from GALILEO-1, a first-in-human clinical trial of FLT201 AAV gene therapy in adult patients with Gaucher Disease Type 1. Presented at: WORLDSymposium, held February 3-7, 2025, in San Diego, California. Poster #318
2. Spur Therapeutics announces positive data from phase 1/2 GALILEO-1 trial of FLT201, its gene therapy candidate for Gaucher disease, at WORLDSymposium. News release. Spur Therapeutics. February 4, 2025. Accessed February 4, 2025. https://www.globenewswire.com/news-release/2025/02/04/3020229/0/en/Spur-Therapeutics-Announces-Positive-Data-from-Phase-1-2-GALILEO-1-Trial-of-FLT201-Its-Gene-Therapy-Candidate-for-Gaucher-Disease-at-WORLDSymposium.html