Sangamo's shares fall on mixed early data from study of gene therapy SB-913 for Hunter syndrome

Shares in Sangamo Therapeutics declined as much as 24 percent Wednesday after the drugmaker unveiled interim Phase I/II study results for SB-913 for the treatment of mucopolysaccharidosis (MPS) type II disease, also known as Hunter syndrome. Despite data suggesting that the experimental gene therapy had an effect on urinary glycosaminoglycans (GAGs), a key biomarker of the condition, increases in the deficient enzyme iduronate-2-sulfatase (IDS) were not able to be detected.

In the CHAMPIONS study, two patients with MPS type II were enrolled into each of three dose cohorts, receiving treatment with a low, medium or high dose of SB-913, all in combination with weekly enzyme replacement therapy. SB-913 is designed to treat MPS type II by using Sangamo's zinc finger nuclease genome editing technology to insert a new copy of the IDS gene into liver cells.

Results were presented at the annual symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) for the first two dose cohorts 16 weeks post-dosing. While results for the low-dose group showed no reductions in levels of GAGs and dermatan sulphate, in the mid-dose cohort, reductions of 50.8 percent and 31.8 percent, respectively, were observed. Meanwhile, decreases in heparan sulphate levels of 23.5 percent and 61.5 percent were seen in the low- and mid-dose cohorts, respectively.

However, Sangamo noted in cohort two, IDS activity "was below the level of quantification of the current assay." The company suggested that an increase in IDS may have not been detected because any that was being produced was rapidly used by cells rather than getting into the bloodstream.

Commenting on the findings, principal investigator Joseph Muenzer said the reductions in key biomarkers were "encouraging," adding "I cannot absolutely say it's a treatment effect." Muenzer continued "this is not proof that this is a successful therapy yet, that these patients had enough gene editing to now supply them with the enzyme they need for the rest of their life." Sangamo's president Sandy Macrae suggested that tests in about five months will reveal more, remarking "the most rational explanation for this is that what we hoped was going to happen has happened."

Meanwhile, Sangamo noted that SB-913 was well tolerated in all dose groups in the study, with no serious adverse events related to the therapy. The drugmaker said that most adverse events were mild and resolved without treatment, while no dose dependence was seen.  

According to Sangamo, two patients in the high-dose cohort have recently been infused, while Muenzer said "we hope to understand the clinical relevance of these changes by conducting a controlled withdrawal of enzyme replacement therapy in patients enrolled in the study soon." The company plans to present longer-term safety and efficacy results from the CHAMPIONS Study in February next year. "We need to see sustained levels for this to be practical. If this only works for six months, that's not very beneficial," Muenzer remarked.

For related analysis, see ViewPoints: CRISPR/Cas9 finally off to the races, with zinc fingers waiting in the wings.

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