Sangamo Therapeutics (SGMO) Announces Evidence of Clinical Benefit in Phase 1/2 STAAR Study in Fabry Disease
Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary data as of October 20, 2022 from the Phase 1/2 STAAR clinical study evaluating isaralgagene civaparvovec, or ST-920. , a proprietary gene therapy product candidate for the treatment of Fabry disease. These data, presenting 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 supplemental cut-off date of November 15, 2022, 13 patients in the dose escalation and expansion phases exhibited supraphysiologic levels of α-Gal A activity, sustained for more than two years for the patient with follow-up. longer. All five patients who began the dose escalation phase in ERT had been successfully withdrawn from ERT and continued to exhibit supraphysiologic levels of α-Gal A activity after discontinuation. No patient has required resumption of ERT treatment to date.
Importantly, there is evidence of a significant reduction in Gb3 substrate at six months in one of the first kidney biopsies taken from this study, along with a significant reduction in urinary podocyte loss. In addition, the study observed a clinically significant and statistically significant increase in mean general health scores, as measured by the SF-36 general health survey.
These updated data will be shared in the 19th annual edition of WORLDSymposium on Friday, February 24, 2023 via an oral presentation in session from 8:00 am to 9:00 am ET, and a poster presentation from 3:00 am to 4:00 pm ET (Poster Ref: 169). These data will also be available on the Sangamo website at Presentations page.
“Fabry is a debilitating disease with a lifelong impact,” said Robert Hopkin, MD, MD, Cincinnati Children’s Hospital Medical Center and investigator of the Phase 1/2 study. “The combination of the results of the first kidney biopsy and the associated urine podocyte data are very encouraging and convincing. Taken together, this exciting data set shows that ST-920 has the potential to improve the lives of patients without the need for cumbersome ERT treatment.”
As of the supplemental cut-off date of November 15, 2022, the nine patients treated in the dose escalation phase in 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 levels ranging from nearly 4-fold to 68-fold mean normal, sustained for more than two years for the patient with the longest follow-up, at the last measurement date . ERT withdrawal was completed for all five patients who began the study on ERT, with continued supraphysiologic levels of α-Gal A activity after ERT withdrawal. All five patients remain without ERT as of February 22, 2023. For naïve and pseudonaïve patients in the dose escalation phase, patients in the highest dose cohort exhibited significantly higher levels of α-Gal activity. A compared with patients in the lower dose cohorts.
As of the supplemental cut-off date of November 15, 2022, the first three patients dosed in the expansion phase at the highest dose level exhibited a rapid increase in α-Gal A activity, sustained until 14 weeks for the patient with the longest follow-up. above, on the last measurement date. The fourth patient had increased within the normal range at four weeks of dosing. The first female patient dosed in the study demonstrated a similar response profile to the male as of the supplemental cut-off date.
Gb3 is a fatty substrate that accumulates in the cells of Fabry disease patients and can cause damage to multiple organs, including the kidneys, heart, and central nervous system. As of the deadline of October 20, 2022, renal biopsy of patient 9 in the dose escalation phase, which demonstrated a large number of Gb3 inclusions and high levels of globotriaosylsphingosine (lyso-Gb3) in plasma at beginning of the study, exhibited a remarkable clearance of 78%. 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 evaluation was performed by two blinded pathologists who independently scored digital images of the kidney sectioned from baseline and 6-month biopsies, adjudicated by a third independent pathologist. Additionally, this patient exhibited a 77% reduction in urinary podocyte loss after 6 months. The significant decrease in renal Gb3 inclusions and the reduction in urinary podocyte loss support a potentially favorable impact on the progression of Fabry nephropathy.
As of the cut-off date of October 20, 2022, the kidney biopsy of patient 8, who exhibited fewer Gb3 inclusions and lower plasma lyso-Gb3 levels at baseline, demonstrated PTC inclusions. stable 6 months after dosing. This patient exhibited a remarkable 97% reduction in urinary podocyte loss after 6 months which, together with the significant increase in α-Gal A activity along with the reduction in lyso-Gb3 after dosing, provides evidence of a potentially favorable effect on Fabry nephropathy.
In addition, changes in patients’ general health scores in the dose escalation phase from baseline at week 52 were statistically significant with an increased mean general health score of 19.6, further demonstrating the potential clinical benefit of isaralgagene civaparvovec. For context, a 3 to 5 point change in any SF-36 score is the minimal clinically important difference.
“We are delighted 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, improvements in kidney biopsy, and the 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 the disease. Fabry,” said Nathalie Dubois-Stringfellow. , Ph.D, Senior Vice President and Chief Development Officer at Sangamo. “We believe we have a best-in-class gene therapy potential and are excited to advance this program to a Phase 3 clinical trial as the next step in our mission to bring an important potential treatment to patients as quickly as possible.”
For naïve and pseudonaïve patients in the dose escalation and expansion phases, where lyso-Gb3 levels started high at baseline (>80 ng/mL), patients experienced a 40-65% reduction in levels after of treatment from October 20. , 2022 cut-off date. For the first time, and at the highest dose level, a 54% reduction in plasma lyso-Gb3 levels was observed when starting levels started below 25 ng/mL. For patients in the dose escalation and dose expansion phases who began the study with ERT, plasma lyso-Gb3 levels after ERT discontinuation remained within the range of levels and variability normally seen in patients. treated with ERT on the cut-off date. In these patients, α-Gal A activity remained elevated and no patient has experienced symptoms requiring resumption of ERT to date.
As of the cut-off date of October 20, 2022, isaralgagene civaparvovec was generally well tolerated in all 13 treated patients in four dose cohorts and expansion groups. No treatment-related adverse events greater than Grade 2 were reported and there were no treatment-related serious adverse events. Prophylactic corticosteroids or other immunomodulatory agents were not administered.
As of the cut-off date of October 20, 2022, an additional four patients have been dosed in the expansion phase for 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 enrolling. We expect dosing to be complete by the end of 2023. Preparations for a potential Phase 3 trial are actively advancing, with an anticipated trial start in late 2023, depending on regulatory interactions. Dosing of the first patient in the Phase 3 trial could begin as early as 2024.
Sangamo will submit our annual report on Form 10-K, which summarizes the updated preliminary results from the Phase 1/2 STAAR clinical study in more detail, and this news release is subject to the additional details provided on the Form 10-K.