ST-920 Gene Therapy Continues to Show Safety, Efficacy in Trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Updated findings in an ongoing Phase 1/2 clinical trial of Sangamo Therapeutics‘ gene therapy ST-920 (isaralgagene civaparvovec) shows the treatment continues to be well tolerated and effective in adults with Fabry disease.

As of the Nov. 19 data cutoff date, all five treated patients enrolled showed normalized levels of alpha-GalA — the enzyme lacking in those with Fabry — and has been sustained for at least a year in the longest treated patients.

The trial, called STAAR, is still recruiting (NCT04046224) up to 48 adults, ages 18 and older, at sites in the U.S. and U.K. Contact information is available here.

“These updated preliminary results demonstrate the potential of [ST-920] gene therapy to address the most challenging symptoms of Fabry disease with a favorable tolerability and safety profile,” Jaya Ganesh, MD, one of the study’s investigators and a professor of genetics at the Icahn School of Medicine at Mount Sinai, said in a press release.

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Fabry is caused by mutations in the GLA gene that lead to production of a faulty alpha-GalA enzyme. When the enzyme can no longer perform its job of breaking down the fatty molecules Gb3 and lyso-Gb3, they accumulate in cells and lead to a range of  disease symptoms.

Enzyme replacement therapy (ERT) provides a functional alpha-GalA enzyme and is a standard Fabry treatment, but it requires lifelong infusions to maintain enzyme levels.

ST-920 is designed to deliver, through a one-time infusion, a healthy version of the GLA gene to the liver, allowing a fully functional alpha-GalA enzyme (a protein that acts as a catalyst) to be continuously produced.

The STAAR study is enrolling Fabry patients who are on ERT, have stopped ERT for at least six months, or who never used this treatment (ERT-naïve).

Previous study results, announced last year, found four patients treated at the lowest two doses — 5 trillion vector genomes per kg of body weight (vg/kg) and 10 trillion vg/kg — showed normal alpha-GalA activity after treatment. At that time, a fifth patient was recently given a third and higher dose of 30 trillion vg/kg.

In its update, Sangamo reports this person had normalized alpha-GalA activity two weeks after treatment. A sixth adult was also treated at this higher dose shortly after the data cutoff date.

“Now with two patients dosed in the third cohort, we are eager to see if the favorable trends exhibited by patients in the first two dose cohorts continue as we … learn more about the emerging profile of this potential treatment,” Ganesh said.

Monitoring of the study’s initial four patients continues, with the two treated at the lowest dose more than a year ago now in long-term follow-up.

Two of the four are continuing to use ERT. At ERT trough, one in the lowest-dosing group showed alpha-GalA levels 15 times above mean normal one year post-treatment, and the other, in the second dosing group, levels 10-fold higher than mean normal at 25 weeks (almost six months) after treatment. A trough is the lowest concentration a therapy reaches before a next dosing.

Among the other two patients, who had stopped ERT use, one treated at lowest dose had levels three-fold above mean normal at one year, and the other (second dose) levels four times higher at 40 weeks post-treatment.

“Withdrawal from ERT has been completed for one patient and is planned for the other patient on ERT, based on the stability of their [alpha]-Gal A activity following treatment,” Sangamo stated in its release.

Across all three doses, ST-920 remains well-tolerated, with few adverse effects reported. Side effects related to treatment were considered mild, with none of the five patients showing a rise in liver enzymes that required steroid treatment.

The gene therapy’s use is also reported to have led to improvements in sweating ability in the first three treated patients, and no progression of heart disease in two patients with cardiomyopathy prior to treatment.

Lyso-Gb3 levels in one patient also significantly dropped, by about 40%  from pre-treatment levels, within 10 weeks of dosing and have been maintained up to 36 weeks, the release stated.

These findings were presented at the 18th Annual WORLDSymposium, and can be viewed on a company webpage.

“We are very pleased with the updated preliminary results from the Phase 1/2 STAAR study and believe that [ST-920] gene therapy has the potential to be a compelling treatment option for patients with Fabry disease, who currently have a burdensome standard of care that … in many cases doesn’t adequately address the underlying disease,” said Rob Schott, MD, Sangamo’s head of development.

Additional STAAR trial  updates are expected through the year, and Sangamo is planning to launch a Phase 3 trial.

“Our focus is completing the Phase 1/2 study and preparing for Phase 3 so that we can evaluate what we hope will be an important therapy in a broader Fabry patient population,” Schott said.