8-K: Sangamo Therapeutics Announces Positive Preliminary Data from Phase 1/2 STAAR Study for Fabry Disease Gene Therapy

Sangamo Therapeutics reports updated clinical data from its Phase 1/2 STAAR study of isaralgagene civaparvovec (ST-920) for Fabry disease, showing sustained benefits and a potential accelerated approval pathway.

Summary

• Sangamo Therapeutics announced updated preliminary clinical data from its Phase 1/2 STAAR study evaluating isaralgagene civaparvovec (ST-920) for Fabry disease.
• The data, as of September 12, 2024, includes 33 patients treated with ST-920.
• The FDA has provided a clear regulatory pathway to Accelerated Approval for ST-920, potentially accelerating approval by approximately three years.
• The FDA agreed that data from the ongoing Phase 1/2 STAAR study can serve as the primary basis for approval under the Accelerated Approval Program, using eGFR slope at 52 weeks as an intermediate clinical endpoint.
• 52-week eGFR slope data is expected in the first half of 2025, with a potential BLA submission anticipated in the second half of 2025.
• ST-920 continues to be generally well-tolerated across all dose cohorts, with most adverse events being mild or moderate.
• All ERT-naive or pseudo-naive patients showed sustained elevated -Gal A activity up to 42 months.
• 17 out of 18 patients were withdrawn from ERT as of the data cutoff, with all 18 remaining off ERT as of February 6, 2025.
• For 23 patients with at least 12 months of follow-up, a mean annualized eGFR slope of 3.061 mL/min/1.73m2/year was observed.
• Significant improvements in disease severity, quality of life, and gastrointestinal symptoms were observed in the 23 patients with at least 12 months of follow-up.
• Following dosing, total Ab or NAb titers decreased markedly in nine patients and became undetectable in seven, or 70% of patients.

Sentiment

Score: 8

Explanation: The document presents positive clinical data and a clear regulatory pathway, suggesting a favorable outlook for ST-920. However, risks related to funding and clinical trial outcomes temper the overall sentiment.

Positives

• The FDA's decision to allow accelerated approval based on Phase 1/2 data significantly shortens the potential time to market for ST-920.
• ST-920 demonstrates a favorable safety profile, with most adverse events being mild or moderate.
• Sustained elevated -Gal A activity was observed in ERT-naive patients for up to 42 months.
• The majority of patients on ERT were able to discontinue therapy and remain off ERT.
• The observed eGFR slope suggests a potential improvement in kidney function.
• Patients experienced improvements in disease severity, quality of life, and gastrointestinal symptoms.
• Antibody levels against -Gal A decreased in a significant portion of patients, potentially reducing immunogenicity issues associated with ERT.

Negatives

• Treatment-emergent serious adverse events were reported in four patients: left arm pain; non-cardiac chest pain, sepsis, stroke and shoulder enthesopathy.
• One patient who began the study on ERT exhibited -Gal A levels below the limit of detection at the time of the data cutoff date.

Risks

• The therapeutic effects observed in the preliminary clinical data may not be durable.
• Final clinical trial data may not validate the safety and efficacy of ST-920.
• The 52-week data may not support a BLA submission, and the 104-week data may not verify the clinical benefit or support FDA approval.
• Sangamo needs substantial additional funding to execute its operating plan and continue as a going concern.
• Macroeconomic factors or financial challenges could impact Sangamo's business and operations.
• The regulatory approval process is unpredictable.
• Technological developments could obviate Sangamo's technologies.
• Sangamo relies on collaborators and may be unable to secure additional collaborations.

Future Outlook

Sangamo anticipates a potential BLA submission in the second half of 2025 and continues to advance business development discussions for a potential ST-920 collaboration agreement.

Industry Context

The development of gene therapies for rare diseases like Fabry disease is a growing area of interest in the pharmaceutical industry, with companies seeking to provide more effective and durable treatments compared to traditional enzyme replacement therapy. Sangamo's progress with ST-920 and the FDA's willingness to consider accelerated approval reflects this trend.

Comparison to Industry Standards

• Other companies developing therapies for Fabry disease include Amicus Therapeutics with Galafold (migalastat), a chaperone therapy, and Takeda with Replagal (agalsidase alfa), an enzyme replacement therapy.
• The observed eGFR slope of 3.061 mL/min/1.73m2/year in Sangamo's study suggests a potential improvement in kidney function, which is a key indicator of disease progression in Fabry disease.
• The ability to withdraw patients from ERT is a significant advantage of gene therapy, as ERT requires frequent infusions and can be associated with immunogenicity issues.
• The long-term follow-up data will be crucial to assess the durability of the treatment effect and the potential for long-term benefits.

Stakeholder Impact

• Shareholders may react positively to the accelerated approval pathway and promising clinical data.
• Patients with Fabry disease could benefit from a new and potentially more effective treatment option.
• Employees of Sangamo may experience increased job security and opportunities for advancement.
• Potential collaboration partners may be more interested in partnering with Sangamo on ST-920.

Next Steps

• Sangamo expects to have 52-week eGFR slope data available in the first half of 2025.
• The company anticipates a potential BLA submission in the second half of 2025.
• Sangamo continues to advance business development discussions for a potential ST-920 collaboration agreement.

Key Dates

Keywords

Fabry disease, Isaralgagene civaparvovec, ST-920, Gene therapy, STAAR study, Sangamo Therapeutics, Accelerated Approval, eGFR, -Gal A activity, Enzyme replacement therapy, ERT, Clinical data