Improving Quality of Life in Patients With Fabry With Gene Therapy


Robert Hopkin, MD, Cincinnati Children’s Hospital Medical Center, discussed unmet needs and patient-reported outcomes from the STAAR trial.

Robert Hopkin, MD

Robert Hopkin, MD

The FDA has aligned with Sangamo Therapeutics on an abbreviated pathway to approval of its gene therapy ST-920 (isaralgagene civaparvovec) for treating Fabry disease.1 The FDA advised, in a Type D meeting, that a single study of ST-290 in 25 patients with Fabry without a control arm or head-to-head with enzyme replacement therapy (ERT), in combination with confirmatory evidence, may be an acceptable pathway to a Biologics License Application (BLA). Sangamo is seeking a collaboration partner to advance the therapy through potential registration and commercialization.

The company recently released data demonstrating disease improvements after treatment from the phase 1/2 STAAR trial (NCT04046224) from 24 participants dosed, which were presented by investigator Robert Hopkin, MD, Cincinnati Children’s Hospital Medical Center, at the 2024 WORLDSymposium, held February 4-9, in San Diego, California. In 13 participants with at least 12 months of follow-up, Fabry outcome survey Mainz Severity Score Index improved (P = .0269), including 38% of participants on ERT. Renal function remained stable, and investigators observed statistically significant improvements on quality-of-life scores, General Health and Physical Component score, and gastrointestinal symptoms (all P <.03.).2

What are unmet needs with current standard of care ERT?

Robert Hopkin, MD: Fabry disease is a rare, X-linked lysosomal storage disorder, and it affects multiple parts of the body. Some of the major complications are very high risk for heart failure, kidney failure and stroke. There's also severe chronic pain, gastrointestinal symptoms like diarrhea and constipation, that are sometimes severe enough to interfere with work. Current treatment requires a great deal of commitment from the patients and only partially addresses these needs. Patients will often lose up to half a day of their life every 2 weeks for enzyme infusions, or they have to take pills on a regular schedule, including fasting before and after taking the medicine. So that's a big burden on the patients. There’s a need to completely address the symptoms and the damage to the organs and trying to simplify the treatment, so it's less of a burden on the patients.

Can you talk about the importance of patient-reported outcomes?

Hopkin: One of the big questions is how does this help the patients, do they feel better? There are now some tools that we use, so we used 3 different patient reported assays that look at severity of Fabry disease symptoms. One of them is called the MSSI. And it's a scale that was developed to rate the severity of Fabry disease in a given patient prior to initiation of treatment. The next one that we used as the SF36, which is a general health related quality of life scale, that is not specific to Fabry disease, but has previously been used in studies of Fabry disease, and then a gastrointestinal symptoms scale. They were developed for very different reasons, very different backgrounds.

Each of them showed significant improvement in the patients treated with this gene therapy, which I think is pretty compelling. If you had improvement in just 1 of those, or you just used 1 scale, how much of that is a placebo effect? These are all subjective things like pain, energy levels, how reliable is this? But when we met measured it from 3 different perspectives, 3 different questionnaires, validated and measured independently, they all came to the same conclusion. And that was sustained over the length of time since treatment, which in these data had to be at least 1 year and out as long as 3 years. That's pretty remarkable. So, we are quite pleased with that.

What are the main takeaways from the STAAR trial?

Hopkin: Bottom line for the STAAR trial, this treatment of Fabry disease has an excellent safety record with no major complications and evidence of improvement in biomarkers, proof of improvement in the health-related quality of life and stable function in the major organ involvement that we've looked at.

The next steps for this trial would be to go to a phase 3 clinical trial looking at a bigger variety of presentations with Fabry disease, and we hope to be able to get that up and running sometime in the near future.

This transcript has been edited for clarity.

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