Sangamo Therapeutics Announces Updated Preliminary Phase 1/2 Data Showing Tolerability and Sustained Elevated α-Gal A Enzyme Activity in Patients With Fabry Disease
- Isaralgagene civaparvovec, or ST-920, continued to be generally well tolerated across three dose cohorts in the five treated patients
- In the first two dose cohorts, all four patients exhibited above normal α-Gal A activity, ranging from 3-fold to 15-fold above mean normal; patients in the first dose cohort have maintained elevated activity for one year and are now in the long-term follow-up study
- In the third dose cohort, the fifth patient exhibited activity within mean normal α-Gal A levels at week 2 and the sixth patient was recently dosed
- Lyso-Gb3 levels remain significantly reduced in the patient who exhibited high baseline levels of this biomarker
“These updated preliminary results demonstrate the potential of isaralgagene civaparvovec gene therapy to address the most challenging symptoms of Fabry disease with a favorable tolerability and safety profile,” said
As of the cutoff date, elevated α-Gal A activity was maintained for the four patients treated in the first two dose cohorts (0.5e13 vg/kg and 1e13 vg/kg) ranging from 3-fold to 15-fold above mean normal at last measurement. For the two patients on enzyme replacement therapy (ERT), α-Gal A activity measured at ERT trough was 15-fold above mean normal at week 52 (Cohort 1) and 10-fold above mean normal at week 25 (Cohort 2). For the two ERT pseudo-naïve patients, α-Gal A activity was 3-fold above mean normal at week 52 (Cohort 1) and 4-fold above mean normal at week 40 (Cohort 2). The two patients in the first dose cohort have now begun the long-term follow-up study. For the first patient in the third dose cohort (3e13 vg/kg), α-Gal A activity has increased into mean normal range at week 2. Withdrawal from ERT has been completed for one patient and is planned for the other patient on ERT, based on the stability of their α-Gal A activity following treatment.
As of the cutoff date, isaralgagene civaparvovec was generally well tolerated across three dose cohorts in the five treated patients. There were no treatment-related adverse events higher than Grade 1 (mild) and no treatment-related serious adverse events. No patients experienced liver enzyme elevations requiring steroid treatment.
“We are very pleased with the updated preliminary results from the Phase 1/2 STAAR study and believe that isaralgagene civaparvovec 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 requires regular and lifelong intravenous treatment, and that in many cases doesn’t adequately address the underlying disease,” said
Improvements in ability to sweat were reported in the first three treated patients. No progression of Fabry cardiomyopathy was observed in the two patients experiencing cardiomyopathy prior to treatment. The one patient with a significant elevation in plasma globotriaosylsphingosine (lyso-Gb3) pre-treatment showed a significant reduction of approximately 40% (from baseline within 10 weeks after dosing, maintained through Week 36) in this biomarker after treatment with isaralgagene civaparvovec. Patients with lower baseline levels of lyso-Gb3 maintained steady levels through the cutoff date.
The sixth patient in the Phase 1/2 STAAR study, who is the second patient in the third dose cohort (3e13 vg/kg), was recently dosed after the cutoff date. Sangamo expects to provide updated results from the STAAR study throughout 2022. Sangamo is currently planning for a Phase 3 clinical trial.
About the STAAR Study
The Phase 1/2 STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate the safety and tolerability of isaralgagene civaparvovec, or ST-920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning. The STAAR study is enrolling patients who are on ERT, are ERT pseudo-naïve (defined as having been off ERT for six or more months), or who are ERT-naïve. The age range of the five patients dosed as of the cutoff date is 22 to 48 years. The
About Fabry Disease
Fabry disease is a lysosomal storage disorder caused by mutations in the galactosidase alpha gene (GLA), which leads to deficient alpha-galactosidase A (α-Gal A) enzyme activity, which is necessary for metabolizing globotriaosylceramide (Gb3). The buildup of Gb3 in the cells can cause serious damage to vital organs, including the kidney, heart, nerves, eyes, gut and skin. Symptoms of Fabry disease can include decreased or absent sweat production, heat intolerance, angiokeratoma (skin blemishes), vision problems, kidney disease, heart failure, gastrointestinal disturbance, mood disorders, neuropathic pain and tingling in the extremities.
This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements relating to the therapeutic potential of isaralgagene civaparvovec (ST-920), including its potential to address the most challenging symptoms of Fabry disease and to become a compelling treatment option for patients with Fabry disease, the potential for the favorable trends exhibited by patients in the first two dose cohorts of the Phase 1/2 STAAR study to continue, Sangamo’s expectation for reporting updated results from the Phase 1/2 STAAR study and the expected timing thereof, plans to discontinue patients on ERT, plans for conducting a Phase 3 clinical trial of isaralgagene civaparvovec, and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to risks and uncertainties that are difficult to predict. Sangamo’s actual results may differ materially and adversely from those expressed. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to: the uncertain timing and unpredictable nature of clinical trials and clinical trial results, including the risks that therapeutic effects observed in preliminary clinical trial results will not be durable in patients and that final Phase 1/2 STAAR study data will not validate the safety and efficacy of isaralgagene civaparvovec; reliance on results of early clinical trials, such as the Phase 1/2 STAAR study, which results are not necessarily predictive of future clinical trial results, including the results of any Phase 3 trial of isaralgagene civaparvovec; the research and development process, including the enrollment, operation and results of clinical trials and the presentation of clinical data; the effects of the evolving COVID-19 pandemic and the impacts of the pandemic on the global business environment, healthcare systems and business and operations of Sangamo, including the initiation and operation of clinical trials; the unpredictable regulatory approval process for product candidates across multiple regulatory authorities; the manufacturing of products and product candidates; the commercialization of approved products; the potential for technological developments that obviate technologies used by Sangamo in isaralgagene civaparvovec and those risks and uncertainties described in Sangamo's filings with the
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