- Sustained elevated expression of alpha-galactosidase A (α-Gal
A) activity maintained for up to three years for the
longest-treated patient as of the data cutoff date.
- All 12 patients withdrawn from enzyme replacement therapy
(ERT) remain off ERT, with sustained elevated α-Gal A activity
observed for up to 19 months as of the data cutoff date.
- Total antibody (Ab) or neutralizing antibody (Nab) titers
against α-Gal A decreased markedly in all seven patients with
antibodies associated with ERT at baseline, and became undetectable
in five.
- In the 13 patients followed for 12 months or more after
treatment, renal function remained stable and significant
improvements in overall disease severity, quality of life (QoL) and
gastrointestinal symptoms compared to baseline were reported.
- Continued favorable safety profile, with no liver function
test (LFT) elevations requiring steroids post-treatment.
- Since the data cutoff date, four additional patients have been
dosed. Enrollment in Phase 1/2 STAAR study is now complete, with
dosing of remaining patients expected in the first half of
2024.
- Productive discussions are continuing with U.S. FDA and other
health authorities on pathways to registration.
Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine
company, today announced updated preliminary data 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. In the largest known clinical gene
therapy program in Fabry disease to date, data from 24 patients
continued to show durable safety and preliminary efficacy data as
of the data cutoff date, which continue to underscore the potential
of isaralgagene civaparvovec as a single-dose treatment option for
Fabry disease.
These data will be shared at the 20th Annual WORLDSymposiumTM in
San Diego, CA on Wednesday, February 7, 2024, via an oral
presentation in the Clinical Applications session from 8:00-9:00
a.m. P.T. and a poster presentation from 3:00-5:00 p.m. P.T.
(Poster Ref: 145). These data will also be available on Sangamo’s
website on the Presentations page.
“Despite the availability of ERT and chaperone therapies, Fabry
disease treatment is burdensome, with some patients still
developing disease progression. To date, ST-920 has been
well-tolerated, and the preliminary data showing sustained
supraphysiologic α-Gal A activity and the ability to discontinue
and remain off ERT are promising,” said Dr. Robert Hopkin, M.D.,
Cincinnati Children’s Hospital Medical Center, and investigator of
the Phase 1/2 STAAR study. “The early improvements reported in
disease severity, quality of life and gastrointestinal symptoms,
together with evidence of reduced immunogenicity, illustrate the
potential of ST-920 as a treatment option for adults with Fabry
disease.”
“We remain encouraged by the emerging safety and efficacy data
supporting the potential durable benefit that ST-920 could offer
patients with Fabry disease as a convenient single-dose treatment
option,” said Lisa Rojkjaer, M.D., Chief Medical Officer of
Sangamo. “We expect to complete dosing of the remaining patients in
the first half of this year as we continue to explore potential
partnerships and other financing options to support the initiation
of a registrational trial.”
Updated Phase 1/2 STAAR Study Results
- As of the September 19, 2023 data cutoff date, 24 patients had
been dosed; as of the treatment date, 13 (54%) were on ERT and 10
(42%) had mild to moderate renal dysfunction at baseline.
Safety:
- Isaralgagene civaparvovec continued to be generally
well-tolerated. The most common adverse events were pyrexia,
headache, COVID-19, fatigue and nasopharyngitis (majority Grade
1/2, with one Grade 3 pyrexia).
- No LFT elevations post-dosing requiring steroids occurred. No
prophylactic steroids or other immunomodulatory agents were
administered, as per protocol.
Efficacy (all dosed patients):
- Patients treated in the dose escalation and dose expansion
phases exhibited sustained, elevated expression of α-Gal A activity
for up to three years in the longest treated patient.
- The ERT naïve or pseudo-naïve patients receiving the highest
dose (2.63 x 1013) showed sustained supraphysiological α-Gal A
activity up to nearly 500 days, with the largest reductions in
plasma globotriaosylsphingosine (lyso-Gb3) levels seen in those
subjects with the highest levels at baseline.
- All 12 patients who began the study on ERT and have
subsequently been withdrawn from ERT, remained off ERT as of the
September 19, 2023 data cutoff date. 11 of these patients continued
to exhibit supraphysiological levels of α-Gal A activity for up to
19 months for the longest treated patient, with one patient
maintaining physiological levels. For the eight ERT-treated
patients receiving the highest dose (2.63 x 1013), plasma lyso-Gb3
levels remained stable following ERT withdrawal for up to one
year.
- Progressive organ impairment linked to immunogenicity remains
an issue with ERT. Seven patients had measurable titers of total
antibodies (Ab) or neutralizing antibodies (Nab) against α-Gal A
associated with ERT at baseline. Following dosing, total Ab or NAb
titers decreased markedly in all seven patients and became
undetectable in five, or 71% of patients. Isaralgagene civaparvovec
did not induce anti-α-Gal A antibodies in seronegative
patients.
Efficacy (13 patients followed for 12
months or more):
- Renal function remained stable, as evidenced by a mean
annualized estimated glomerular filtration rate (eGFR) slope of
-0.915 mL/min/1.73m2/year.
- Statistically significant improvements in disease severity were
reported in the Fabry Outcome Survey adaptation of the Mainz
Severity Score Index (FOS-MSSI) age-adjusted score at week 52
(p=0.0269).
- Four patients improved their overall FOS-MSSI disease category
(e.g., improving from ‘Moderate’ to ‘Mild’ categorization of Fabry
disease compared to their baseline category) at week 52. Three of
these individuals were on ERT at baseline, demonstrating the
potential clinical benefit of isaralgagene civaparvovec over the
currently approved standard of care.
- Significant improvements in the short form-36 (SF-36) QoL
scores were reported, with mean changes in the General Health and
Physical Component scores of 10.5 (p=0.0158) and 4.395 (p=0.0140),
respectively, at week 52. For context, a 3- to 5-point change on
any SF-36 score is the minimally clinically important
difference.
- Significant improvements in the gastrointestinal symptom rating
scale (GSRS) compared to baseline were also reported at week 52
(p=0.0226).
- Collectively, we believe these data support the potential for
isaralgagene civaparvovec to be a promising new treatment option
for previously treated and untreated patients with Fabry
disease.
Since the September 19, 2023 data cutoff date, four additional
patients have been dosed in the expansion phase to achieve a total
of 28 treated patients, and one additional patient has been
withdrawn from ERT. All 13 patients withdrawn from ERT remain off
ERT as of February 5, 2024. Screening and enrollment are complete
in the Phase 1/2 STAAR study and dosing of the remaining enrolled
patients is expected in the first half of 2024. The Company is
deferring additional investments in planning for a registrational
trial until a collaboration partnership or financing is secured.
Productive discussions continue with the U.S. FDA and other health
authorities on pathways to registration.
Additionally, another oral presentation and poster presentation
at WorldSymposiumTM will feature pharmacology and safety data from
the Company’s nonclinical work for isaralgagene civaparvovec. The
data demonstrated supraphysiological plasma and liver α-Gal A
activity in mouse models, supporting Phase 1/2 and potential Phase
3 clinical dosing. The oral presentation will take place at
WORLDSymposiumTM on Thursday, February 8, 2024, in the Contemporary
Forum session from 8:00-9:00 a.m. P.T. and a poster presentation
will be from 3:00-5:00 p.m. P.T. (Poster Ref: 224).
A Current Report on Form 8-K summarizing the updated preliminary
results from the Phase 1/2 STAAR study in more detail will be filed
by Sangamo, and this press release is subject to the further detail
provided in the Form 8-K.
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 enrolled 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 U.S. Food and Drug
Administration has granted Orphan Drug, Fast Track and RMAT
designations to isaralgagene civaparvovec, which has also received
Orphan Medicinal Product designation from the European Medicines
Agency.
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.
About Sangamo Therapeutics
Sangamo Therapeutics is a genomic medicine company dedicated to
translating ground-breaking science into medicines that transform
the lives of patients and families afflicted with serious
neurological diseases who do not have adequate or any treatment
options. Sangamo’s zinc finger epigenetic regulators are ideally
suited to potentially address devastating neurological disorders
and Sangamo’s capsid discovery platform is making progress toward
potentially expanding delivery beyond currently available
intrathecal delivery capsids, including in the central nervous
system. Sangamo’s pipeline also includes multiple partnered
programs and programs with opportunities for partnership and
investment. To learn more, visit www.sangamo.com and connect with
us on LinkedIn and Twitter.
Forward-Looking Statements
This press release contains forward-looking statements regarding
our current expectations. These forward-looking statements include,
without limitation, statements relating to: the safety and efficacy
and therapeutic and commercial potential of isaralgagene
civaparvovec, the anticipated plans and timelines for conducting
our ongoing and potential future clinical trials and presenting
clinical data from our clinical trials, expectations regarding the
conclusion of dosing in our Phase 1/2 STAAR study, the anticipated
advancement of isaralgagene civaparvovec to late-stage development,
including Sangamo’s plans to seek a potential partner or additional
financing to proceed with potential future Phase 3 trials of
isaralgagene civaparvovec and the timing thereof, our plans to
participate in industry and investor conferences, and other
statements that are not historical fact. These statements are not
guarantees of future performance and are subject to certain risks
and uncertainties that are difficult to predict. Factors that could
cause actual results to differ include, but are not limited to,
risks and uncertainties related to our lack of capital resources to
fully develop, obtain regulatory approval for and commercialize our
product candidates, including our ability to secure the funding
required to initiate a potential Phase 3 trial of isaralgagene
civaparvovec in a timely manner or at all; our need for substantial
additional funding to execute our operating plan and to continue to
operate as a going concern; the effects of macroeconomic factors or
financial challenges, including as a result of the ongoing overseas
conflict, current or potential future bank failures, inflation and
rising interest rates, on the global business environment,
healthcare systems and business and operations of Sangamo and our
collaborators, including the operation of clinical trials; the
research and development process, including the operation and
results of clinical trials and the presentation of clinical data;
the impacts of clinical trial delays, pauses and holds on clinical
trial timelines and commercialization of product candidates; the
uncertain timing and unpredictable nature of clinical trial
results, including the risk that the therapeutic effects observed
in the latest preliminary clinical data from the Phase 1/2 STAAR
study will not be durable in patients and that final clinical trial
data from the study will not validate the safety and efficacy of
isaralgagene civaparvovec, and that the patients withdrawn from ERT
will remain off ERT; the unpredictable regulatory approval process
for product candidates across multiple regulatory authorities;
reliance on results of early clinical trials, which results are not
necessarily predictive of future clinical trial results, including
the results of any Phase 3 trial of our product candidates; the
potential for technological developments that obviate technologies
used by Sangamo; our reliance on collaborators and our potential
inability to secure additional collaborations, and our ability to
achieve expected future financial performance.
There can be no assurance that we and our current or potential
future collaborators will be able to develop commercially viable
products. Actual results may differ materially from those projected
in these forward-looking statements due to the risks and
uncertainties described above and other risks and uncertainties
that exist in the operations and business environments of Sangamo
and our collaborators. These risks and uncertainties are described
more fully in our Securities and Exchange Commission, or SEC,
filings and reports, including in our Annual Report on Form 10-K
for the year ended December 31, 2022, as supplemented by our
Quarterly Report on Form 10-Q for the quarter ended September 30,
2023, each filed with the SEC, and future filings and reports that
Sangamo makes from time to time with the SEC. Forward-looking
statements contained in this announcement are made as of this date,
and we undertake no duty to update such information except as
required under applicable law.
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Investor Relations & Media
Inquiries Louise Wilkie ir@sangamo.com media@sangamo.com
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