Novel Enzyme Replacement Therapy ISU303 Shows Promise in Small Trial

ISU Abxis therapy shows efficacy, good safety profile in patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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ISU303, an experimental enzyme replacement therapy for Fabry disease, showed a good safety profile and some promising signs of efficacy in a small clinical trial in Asia, according to researchers.

The “results suggest that ISU303 is safe and effective and [may be an] alternative ERT for [Fabry disease],” the researchers wrote.

The study, titled “A phase II, multicenter, open-label trial to evaluate the safety and efficacy of ISU303 (Agalsidase beta) in patients with Fabry disease,” was published in the journal Medicine.

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Enzyme replacement therapy for Fabry

Fabry disease is caused by genetic mutations in the gene that provides instructions for making the alpha-galactosidase A (Gal A) enzyme. Lack of functional Gal A leads to the toxic buildup of certain fatty molecules — particularly globotriaosylceramide (Gb3) — inside cells, ultimately damaging tissues.

Enzyme replacement therapy, or ERT, is a treatment strategy that involves delivering a functional version of the missing enzyme to patients.

In the U.S., the only approved ERT is Fabrazyme (agalsidase beta), sold by Sanofi Genzyme. Another ERT called Replagal (agalsidase alfa), sold by Takeda, is approved in many other countries but not in the U.S.

ISU303 is a novel agalsidase beta form of ERT that is being developed by the Korean company ISU Abxis. It is produced using a Chinese hamster ovary cell line, in a similar manner to Fabrazyme.

This clinical trial enrolled 10 people with Fabry disease at centers in South Korea. Among the patients, seven were men, three were women, and the average age was 33. Eight patients had received previous ERT with Fabrazyme, while the other two were newly diagnosed and had not been on enzyme replacement therapy before.

The participants were treated with ISU303 for six months. The therapy was administered via infusions every other week, with each infusion lasting 4–6 hours. Nine patients completed the study; one withdrew early due to an unexpected pregnancy.

At the start of the study, the average level of Gb3 in participants’ blood was 8.1 micrograms per milliliter (ug/mL). After 22 weeks (about 5.5 months) of treatment with ISU303, the level decreased significantly to 4.09 ug/mL. Gb3 levels below 9.9 ug/mL are considered normal.

Average levels of Gb3 in urine also decreased significantly following ISU303 treatment. Levels of a related molecule called lyso-Gb3 did not change significantly in blood or urine.

Measures of heart function and life quality were mostly unchanged over the course of the study. Measures of kidney function and patient-reported assessments of pain showed trends toward improvement, though the differences did not reach statistical significance.

Overall, ISU303 was well-tolerated during the study, with no serious side effects reported. Common side effects related to treatment included fever, chills, dizziness, and drowsiness.

“Treatment with ISU303 significantly reduced plasma Gb3 and had tolerable adverse events during the observation period. In addition, it stabilized the disease progression regarding renal and cardiac dysfunction and pain severity,” the researchers concluded.

Based on these findings, “we anticipate that ISU303 will be comparable to original agalsidase beta [Fabrazyme] and a treatment option for patients” with Fabry disease, the researchers said.