8-K: Sangamo's Fabry Gene Therapy Shows Positive Clinical Data

Sangamo Therapeutics announced updated positive clinical data from its Phase 1/2 STAAR study for isaralgagene civaparvovec, a gene therapy for Fabry disease, supporting its accelerated approval pathway.

Summary

• Updated clinical data from the registrational Phase 1/2 STAAR study for isaralgagene civaparvovec (ST-920), a gene therapy for Fabry disease, was presented at ICIEM2025.
• The data, with a cutoff date of April 10, 2025, included 33 treated patients, with 32 having at least 52 weeks of follow-up.
• Positive mean annualized eGFR slopes were observed at 52 weeks (1.965 mL/min/1.73m2/year) and 104 weeks (1.747 mL/min/1.73m2/year), comparing favorably to approved Fabry treatments.
• Cardiac function remained stable, and ERT-naive patients showed normal to supraphysiological alpha-galactosidase A (α-Gal A) activity and reduced/stabilized lyso-Gb3 levels.
• All 18 patients initially on ERT were able to safely withdraw from ERT, with one patient off ERT for over three years, though one patient resumed ERT after the data cutoff.
• Significant improvements were reported in disease severity (FOS-MSSI), quality of life (SF-36 scores), and gastrointestinal symptoms (GSRS).
• Immunogenicity improved, with 80% of patients showing undetectable pre-existing antibodies against α-Gal A, and no new antibodies induced in seronegative patients.
• Isaralgagene civaparvovec was generally well-tolerated, with most adverse events (AEs) being mild or moderate, and no study discontinuations or deaths due to AEs.
• Sangamo is preparing a Biologics License Application (BLA) under the Accelerated Approval pathway, with an intended submission as early as Q1 2026, contingent on securing adequate additional funding.

Sentiment

Score: 7

Explanation: The clinical data presented for isaralgagene civaparvovec is overwhelmingly positive, demonstrating favorable efficacy and safety profiles that support an accelerated approval pathway. This represents a significant scientific and clinical milestone. However, the explicit and severe financial risks, including the dependency on securing 'adequate additional funding' for BLA submission and the 'going concern' warning, introduce substantial uncertainty regarding the company's operational continuity and ability to capitalize on these clinical successes.

Positives

• Positive mean annualized eGFR slopes of 1.965 mL/min/1.73m2/year at 52 weeks and 1.747 mL/min/1.73m2/year at 104 weeks were observed, comparing favorably to approved Fabry treatments.
• Stable cardiac function was observed across all patients, including those with up to four years of data, with stable end-diastolic/systolic volume, left ventricular mass, and T1/T2 mapping.
• ERT-naive or pseudo-naive patients (n=15) showed normal to supraphysiological levels of α-Gal A activity for up to 54 months, accompanied by reduction and/or long-term stabilization of lyso-Gb3 levels.
• All 18 patients who began the study on ERT were able to safely withdraw from ERT, with one patient remaining off ERT for over three years.
• Significant improvements in disease severity (69% of patients improved FOS-MSSI score at 12 months) and quality of life (statistically significant improvements in SF-36 scores, exceeding minimally clinically important differences) were observed.
• Significant improvements in GI symptoms were demonstrated by the GSRS, with a mean change from baseline at Week 52 of -0.24 (p=0.0087) and a mean change in Diarrhea score of -0.50 (p=0.0048).
• Pre-existing antibodies against α-Gal A decreased markedly in 9 patients and became undetectable in 8 (80%) of those with measurable titers at baseline, and no new antibodies were induced in seronegative patients.
• Isaralgagene civaparvovec was generally well-tolerated across all dose cohorts without the need for preconditioning, with the majority of AEs being mild (Grade 1) or moderate (Grade 2).
• No AEs led to study discontinuation, and no deaths were reported.

Negatives

• One patient who had withdrawn from ERT decided to resume ERT after the April 10, 2025 data cutoff date, despite maintaining supraphysiological α-Gal A activity and generally stable lyso-Gb3 levels.
• Seven treatment-emergent serious AEs (TESAEs) were reported in five patients, including left arm pain, non-cardiac chest pain, sepsis, shoulder enthesopathy, pain in extremity, cerebrovascular accident, and brain stem stroke, all graded as Grade 2 or 3.

Risks

• Lack of capital resources and need for substantial additional funding to execute the operating plan and continue as a going concern.
• Risk of being unable to obtain substantial additional funding on acceptable terms or at all, or to secure collaboration partners necessary to advance preclinical and clinical programs, particularly for the Fabry disease program.
• Potential requirement to cease operations entirely, liquidate assets, and/or seek protection under the U.S. Bankruptcy Code if adequate funding is not secured.
• Uncertain timing and unpredictable nature of clinical trial results, including the risk that therapeutic effects observed in the STAAR study may not be durable.
• Risk that final clinical trial data from the STAAR study will not validate the safety and efficacy of isaralgagene civaparvovec, or that 104-week data will not verify clinical benefit or support FDA approval.
• Risk that patients withdrawn from ERT may not remain off ERT.
• Effects of macroeconomic factors or financial challenges, including ongoing overseas conflicts, tariffs, geopolitical instability, inflation, and fluctuations in interest rates, on the global business environment and Sangamo's operations.
• Risks associated with the research and development process and the unpredictable regulatory approval process for product candidates across multiple regulatory authorities.
• Reliance on results of early clinical trials, which are not necessarily predictive of future clinical trial results, including those of any registrational trial.
• Potential for technological developments that could obviate technologies used by Sangamo.
• Reliance on collaborators and potential inability to secure additional collaborations.
• Ability to achieve expected future financial performance.

Future Outlook

Sangamo intends to submit a Biologics License Application (BLA) for isaralgagene civaparvovec as early as the first quarter of 2026, contingent on securing adequate additional funding. The company is also actively engaging in business development negotiations for a potential Fabry commercialization agreement.

Management Comments

• Sangamo is advancing Biologics License Application (BLA) preparation activities for isaralgagene civaparvovec under the Accelerated Approval pathway.
• Sangamo is continuing to engage in business development negotiations for a potential Fabry commercialization agreement.
• Sangamo intends to submit a BLA for isaralgagene civaparvovec as early as the first quarter of 2026, subject to its ability to secure adequate additional funding.

Industry Context

The development of gene therapies like isaralgagene civaparvovec represents a significant advancement in the treatment of rare genetic disorders such as Fabry disease, which currently relies on enzyme replacement therapy (ERT). Successful progression through the Accelerated Approval pathway could position Sangamo as a leader in this specialized therapeutic area, offering a potentially transformative, single-dose treatment option that could reduce the burden of chronic ERT infusions and improve patient outcomes. This aligns with broader industry trends towards precision medicine and gene-editing technologies for inherited diseases.

Comparison to Industry Standards

• The observed mean annualized eGFR slopes of 1.965 mL/min/1.73m2/year at 52 weeks and 1.747 mL/min/1.73m2/year at 104 weeks compare favorably to a meta-analysis of publications of approved Fabry treatments, including Fabrazyme, Replagal, and Galafold. The upper confidence limit (UCL) of the 95% CI for the historical comparator was -1.055 mL/min/1.73m2/year, indicating a positive difference for isaralgagene civaparvovec.
• Statistically significant improvements in SF-36 Quality of Life scores, such as a mean change in role-physical score of +14.8, significantly exceed the minimally clinically important difference of 3-5 points, suggesting a substantial positive impact on patient well-being compared to general clinical benchmarks.

Stakeholder Impact

• **Patients with Fabry disease**: The positive clinical data offers significant hope for a new, potentially transformative gene therapy that could provide sustained benefits, reduce or eliminate the need for chronic enzyme replacement therapy (ERT), and substantially improve quality of life.
• **Shareholders**: The strong clinical results are a positive indicator for the company's pipeline and future potential. However, the explicit and severe financial risks, including the need for substantial additional funding and the 'going concern' warning, introduce significant uncertainty and could negatively impact share price if not addressed.
• **Employees**: Continued progress in clinical development and the potential for commercialization could secure jobs and offer future growth opportunities, but the financial risks pose a threat to job security.
• **Regulatory authorities (FDA)**: The data supports the accelerated approval pathway, indicating a potential new, effective treatment option for a rare disease with unmet medical needs, which could expedite regulatory review.
• **Potential Commercialization Partners**: The positive clinical data makes isaralgagene civaparvovec an attractive asset for potential partners, but the company's funding challenges might influence negotiation terms.

Next Steps

• Continue Biologics License Application (BLA) preparation activities for isaralgagene civaparvovec.
• Engage in business development negotiations for a potential Fabry commercialization agreement.
• Submit a BLA for isaralgagene civaparvovec as early as the first quarter of 2026, contingent on securing adequate additional funding.
• Continue the separate long-term follow-up study to monitor treated patients for up to five years following treatment.

Key Dates

Recommendation

While the clinical data for isaralgagene civaparvovec is highly promising and supports an accelerated approval pathway, the explicit and severe financial risks, including the need for substantial additional funding to even submit the BLA and the 'going concern' warning, introduce significant uncertainty. The positive clinical results are largely offset by the capital raise dependency and potential for cessation of operations, making a 'hold' recommendation appropriate until the funding situation becomes clearer and the company's financial viability is more assured. Investors should monitor developments regarding capital raises and commercialization partnerships closely.

Keywords

Fabry disease, gene therapy, isaralgagene civaparvovec, ST-920, rare disease, clinical trial, Phase 1/2 STAAR study, FDA Accelerated Approval, eGFR, alpha-galactosidase A, lyso-Gb3, enzyme replacement therapy, Sangamo Therapeutics