Sangamo Therapeutics Announces Evidence of Clinical Benefit in Phase 1/2 STAAR Study in Fabry Disease By Investing.com

Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary data as of the October 20, 2022 cutoff date from the Phase 1/2 STAAR clinical study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned gene therapy product candidate for the treatment of Fabry disease. These data, which present new biomarker data and results from the first kidney biopsies in this study, indicate evidence of clinical benefit for isaralgagene civaparvovec in Fabry disease.

As of the November 15, 2022 supplemental cutoff date, 13 patients across the dose escalation and expansion phases exhibited supraphysiological levels of α-Gal A activity, sustained for over two years for the patient with the longest follow-up. All five patients who began the dose escalation phase on ERT had been successfully withdrawn from ERT and continued to exhibit supraphysiological levels of α-Gal A activity following withdrawal. No patient has required the resumption of ERT treatment to date.

Importantly, there is evidence of significant Gb3 substrate reduction at six months in one of the first kidney biopsies taken from this study, along with a significant reduction in urine podocyte loss. In addition, the study observed a clinically meaningful and statistically significant increase in mean general health scores, as measured by the SF-36 General Health survey.

These updated data will be shared at the 19th Annual WORLDSymposium on Friday, February 24, 2023 via an oral presentation in the session from 8:00-9:00am Eastern Time and a poster presentation from 3:00-4:00pm Eastern Time (Poster Ref: 169). These data will also be available on Sangamo’s website on the Presentations page.

“Fabry is a debilitating disease with life-long impact,” said Dr. Robert Hopkin, MD, Cincinnati Children’s Hospital Medical Center, and investigator of the Phase 1/2 study. “The combination of the first kidney biopsy results and the associated urine podocyte data are highly encouraging and compelling. As a whole, this exciting dataset shows that ST-920 has the potential to improve the lives of patients without the need for burdensome ERT treatment.”

As of the November 15, 2022 supplemental cutoff date, all nine patients treated in the dose escalation phase across the four dose cohorts (0.5×1013 vg/kg, 1×1013 vg/kg, 3×1013 vg/kg and 5×1013 vg/kg) exhibited elevated α-Gal A activity ranging from nearly 4-fold to 68-fold of mean normal, sustained for over two years for the patient with the longest follow-up, at the last date of measurement. ERT withdrawal was completed for all five patients who began the study on ERT, with continued supraphysiological levels of α-Gal A activity following ERT withdrawal. All five patients remain off ERT as of February 22, 2023. For naïve and pseudo-naïve patients in the dose escalation phase, patients in the highest dose cohort exhibited significantly higher levels of α-Gal A activity compared to those patients in lower dose cohorts.

As of the November 15, 2022 supplemental cutoff date, the first three patients dosed in the expansion phase at the highest dose level exhibited a rapid increase in α-Gal A activity, sustained for up to 14 weeks for the patient with the longest follow-up, at the last date of measurement. The fourth patient had increased to within normal range at four weeks of dosing. The first female patient dosed in the study demonstrated a similar response profile to males as of the supplemental cutoff date.

Gb3 is a fatty substrate that accumulates in the cells of Fabry disease patients and can result in damage to multiple organs, including the kidneys, heart and central nervous system. As of the October 20, 2022 cutoff date, the kidney biopsy for patient 9 in the dose escalation phase – who demonstrated a high number of Gb3 inclusions and high levels of plasma globotriaosylsphingosine (lyso-Gb3) at baseline – exhibited a notable 78% clearance in Gb3 inclusions per peritubular capillary (or PTC) from an average of 8.7 inclusions per PTC at baseline to 1.9 inclusions per PTC, 6 months after dosing. This assessment was made by two blinded pathologists who independently scored digital images of the sectioned kidney from baseline and 6-month biopsies, adjudicated by a third independent pathologist. In addition, this patient exhibited a 77% reduction in urinary podocyte loss after 6 months. The significant decrease in renal Gb3 inclusions and the reduction in urine podocyte loss supports a potentially favorable impact on progression of Fabry nephropathy.

As of the October 20, 2022 cutoff date, the kidney biopsy for patient 8 – who exhibited a lower number of Gb3 inclusions and lower levels of plasma lyso-Gb3 at baseline – demonstrated stable PTC inclusions 6-months post dosing. This patient exhibited a notable 97% reduction in urinary podocyte loss after 6-months which, coupled with the significant increase in a-Gal A activity along with reduction in lyso-Gb3 after dosing, provides evidence of a potentially favorable effect on Fabry nephropathy.

In addition, changes in General Health Scores for patients in the dose escalation phase from baseline at Week 52 were statistically significant with a mean increased General Health Score of 19.6, further demonstrating the potential clinical benefit of isaralgagene civaparvovec. For context, a 3- to 5-point change on any SF-36 score is the minimally clinically important difference.

“We are thrilled with these data, which we believe demonstrate the importance of ST-920 as a potential gene therapy to treat the underlying pathology of Fabry disease. Taken together, the updated biomarker data, kidney biopsy improvements and SF-36 results suggest a promising path forward in our efforts to develop a gene therapy that has the potential to transform the lives of patients living with Fabry disease,” said Nathalie Dubois-Stringfellow, Ph.D, Sangamo’s Senior Vice President, Chief Development Officer. “We believe that we have a potential best-in-class gene therapy and are excited to advance this program into a Phase 3 clinical trial as the next step in our mission to deliver an important potential treatment to patients as quickly as possible.”

For naïve and pseudo-naïve patients in the dose escalation and expansion phases, where levels of lyso-Gb3 started high at baseline (>80 ng/mL), patients experienced a 40-65% reduction in levels following treatment as of the October 20, 2022 cutoff date. For the first time, and at the highest dose level, a 54% reduction in plasma lyso-Gb3 levels was observed where baseline levels started below 25 ng/mL. For patients in the dose escalation and expansion phases who began the study on ERT, plasma lyso-Gb3 levels following ERT withdrawal remained within the range of levels and variability normally observed in patients treated with ERT as of the cutoff date. In these patients, α-Gal A activity remained elevated, and no patient experienced symptoms requiring the resumption of ERT to date.

As of the October 20, 2022 cutoff date, isaralgagene civaparvovec was generally well tolerated in the 13 treated patients across four dose cohorts and the expansion groups. No treatment-related adverse events greater than a Grade 2 were reported and there were no treatment-related serious adverse events. No prophylactic corticosteroids or other immune modulating agents were administered.

Since the October 20, 2022 cutoff date, a further four patients have been dosed in the expansion phase to achieve a total of 17, and an additional two patients have been withdrawn from ERT. Dosing of the remaining patients in the expansion phase of the Phase 1/2 STAAR study is ongoing, with a total of 20 sites active and recruiting. We expect dosing to conclude by the end of 2023. Preparations for a potential Phase 3 trial actively progress, with a trial start anticipated by the end of 2023, depending on regulatory interactions. Dosing of the first patient in the Phase 3 trial could begin as early as the first part of 2024.

Our Annual Report on Form 10-K summarizing the updated preliminary results from the Phase 1/2 STAAR clinical study in more detail will be filed by Sangamo, and this press release is subject to the further detail provided in the Form 10-K.