Giroctocogene fitelparvovec trial meets primary
and key secondary objectives of superiority compared to
prophylaxis
Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine
company, today reported on Pfizer Inc.’s announcement of positive
topline results from the Phase 3 AFFINE trial (NCT04370054)
evaluating giroctocogene fitelparvovec, an investigational gene
therapy that Sangamo is co-developing with and licensing to Pfizer
for the treatment of adults with moderately severe to severe
hemophilia A.
Sangamo is eligible to earn from Pfizer up to $220 million in
milestone payments upon the achievement of certain regulatory and
commercial milestones for giroctocogene fitelparvovec and product
sales royalties of 14% - 20% if giroctocogene fitelparvovec is
approved and commercialized, subject to certain reductions.
Pfizer reported that the AFFINE trial achieved its primary
objective of non-inferiority, as well as superiority, of total
annualized bleeding rate (ABR) from Week 12 through at least 15
months of follow up post-infusion compared with routine Factor VIII
(FVIII) replacement prophylaxis treatment. Following a single 3e13
vg/kg dose, giroctocogene fitelparvovec demonstrated a
statistically significant reduction in mean total ABR compared to
the pre-infusion period (1.24 vs 4.73; one-sided
p-value=0.0040).
Key secondary endpoints as defined by the trial protocol were
met and also demonstrated superiority compared to prophylaxis. 84%
of participants maintained FVIII activity >5% at 15 months
post-infusion (one-sided p-value = 0.0086) with the majority of
participants having FVIII activity ≥15%, and the mean treated ABR
showed a statistically significant 98.3% reduction from 4.08 in the
pre-infusion period to 0.07 post-infusion (from Week 12 up to at
least 15 months [15-44 months]; one-sided p-value < 0.0001).
Throughout the trial, among all dosed participants, one participant
(1.3%) returned to prophylaxis post-infusion.
In the AFFINE trial, giroctocogene fitelparvovec was generally
well tolerated. Transiently elevated FVIII levels ≥150% were
observed in 49.3% of dosed participants, as measured via
chromogenic assay, with no impact on efficacy and safety results.
Serious adverse events were reported in 15 patients (20%),
including 13 events reported by 10 patients (13.3%) assessed as
related to treatment. Treatment-related adverse events generally
resolved in response to clinical management.
“For people living with hemophilia A, the physical and emotional
impact of needing to prevent and treat bleeding episodes through
frequent IV infusions or injections cannot be underestimated,” said
Professor Andrew Leavitt M.D., AFFINE lead investigator,
Departments of Laboratory Medicine and Medicine Division of
Hematology/Oncology Director, Adult Hemophilia Treatment Center,
University of California, San Francisco, CA. “I’m excited by the
strength of these positive results from the AFFINE trial that show
giroctocogene fitelparvovec was generally well tolerated, and
demonstrate the transformative potential of this gene therapy
candidate to provide superior bleed protection compared with
routine FVIII prophylaxis, while helping relieve the treatment
burden for people living with hemophilia A.”
Giroctocogene fitelparvovec is a novel, investigational gene
therapy that contains a bio-engineered AAV6 capsid and a modified
B-domain deleted human coagulation FVIII gene. The goal of this
investigational treatment for people living with hemophilia A is
that a single infusion of giroctocogene fitelparvovec may allow
them to produce FVIII themselves for an extended period of time,
provide bleed protection and reduce the need for routine
prophylaxis with intravenous (IV) infusions or
injections.i,ii,iii,iv
“We are thrilled with the positive topline results from the
Phase 3 AFFINE trial, which demonstrated the potential of
giroctocogene fitelparvovec as a one-time gene therapy for people
with hemophilia A and provide a potential alternative to the
current burden of disease management,” said Nathalie
Dubois-Stringfellow, Ph.D, Chief Development Officer at Sangamo.
“These impressive results further validate the power of our genomic
technologies and take us one step closer towards what could become
Sangamo’s first medicine commercially available to patients. We
greatly appreciate Pfizer’s strong leadership of this important
program and look forward to their discussions of these data with
regulatory authorities.”
In this Phase 3 trial, eligible trial participants were
initially enrolled in a lead-in study (NCT03587116) and upon
successful completion, were enrolled into the AFFINE trial where
they received a one-time 3e13 vg/kg dose of giroctocogene
fitelparvovec by IV infusion. Participants in the AFFINE trial were
screened with a validated assay designed to identify individuals
who test negative for neutralizing antibodies to the gene therapy
vector. Clinical trial participants will be evaluated in AFFINE
over the course of five years, and up to a total of 15 years as
part of a long-term follow-up trial.
Pfizer reported that analyses of the full Phase 3 dataset from
the AFFINE trial are ongoing and additional data will be presented
at upcoming medical meetings. Giroctocogene fitelparvovec has been
granted Fast Track and Regenerative Medicine Advanced Therapy
designations from the U.S. Food and Drug Administration (FDA), as
well as Orphan Drug designations in the U.S. and the European
Union. Pfizer reported that it will discuss these data with
regulatory authorities in the coming months. Pfizer recently
received FDA approval for BEQVEZ™ (fidanocogene elaparvovec), its
hemophilia B gene therapy for eligible patients.
About the AFFINE Trial
The Phase 3 AFFINE (NCT04370054) trial is an open-label,
multicenter, single-arm trial to evaluate the efficacy and safety
of a single infusion of giroctocogene fitelparvovec in adult male
participants (n=75 dosed participants) with moderately severe to
severe hemophilia A. Trial participants included in the assessments
of the key endpoints of the primary efficacy analysis (n=50)
completed a minimum six months of routine FVIII replacement
prophylaxis therapy during the lead-in study (NCT03587116)
providing data to compare with post giroctocogene fitelparvovec
treatment.
The primary endpoint measures the total ABR (spontaneous and
traumatic bleedings, treated and untreated) from Week 12 through at
least 15 months following treatment with giroctocogene
fitelparvovec compared to total ABR on prior FVIII prophylaxis
replacement therapy. For more information, visit
clinicaltrials.gov.
Giroctocogene fitelparvovec is being developed as part of a
collaboration agreement for the global development and
commercialization of gene therapies for hemophilia A between
Sangamo Therapeutics and Pfizer. In late 2019, Sangamo transferred
the manufacturing technology and the Investigational New Drug
application to Pfizer. Under the agreement, Pfizer assumed
responsibility for pivotal studies, any regulatory activities, and
potential global commercialization of giroctocogene
fitelparvovec.
About Hemophilia A
Hemophilia is an inherited, rare bleeding disorder that causes
people to bleed for longer than normal due to a deficiency of a
protein required for normal blood clotting, known as clotting
Factor VIII (FVIII) in hemophilia A. The severity of hemophilia is
determined by the amount of the factor in the blood. The lower the
amount of the factor, the more likely it is that bleeding will
occur, which can lead to serious health problems.v
Hemophilia A occurs in approximately 25 in every 100,000 male
births worldwide.vi Approximately 55-75% of males with hemophilia A
have a moderate to severe form of the disease.vii For people who
live with hemophilia A, there is an increased risk of spontaneous
bleeding as well as bleeding following injuries or surgery.v It is
a lifelong disease that requires constant monitoring and
therapy.viii
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 believes that its zinc finger epigenetic
regulators are ideally suited to potentially address devastating
neurological disorders and that its capsid discovery platform can
potentially expand 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/X.
Forward-Looking Statements
This release contains forward-looking statements regarding
Sangamo's current expectations. These forward-looking statements
include, without limitation, statements regarding, the potential of
giroctocogene fitelparvovec to provide superior bleed protection
compared with routine FVIII replacement therapy, that a single
infusion of giroctocogene fitelparvovec may allow patients to
produce FVIII themselves for an extended period of time, Pfizer’s
continued advancements of the giroctocogene fitelparvovec program,
the potential for Pfizer to complete clinical development,
regulatory interactions, manufacturing and global commercialization
of any resulting products, the potential for Sangamo to receive
development and commercial milestone payments and royalties, 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 in
these forward-looking statements. Factors that could cause actual
results to differ include, but are not limited to, risks and
uncertainties related to: the global business environment,
healthcare systems and the business and operations of Sangamo and
Pfizer,; the research and development process, including the
results of preclinical studies and clinical trials; the 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 and its partners; the potential for Pfizer to breach or
terminate its collaboration agreement with Sangamo; the potential
for Sangamo to fail to realize its expected benefits from the
Pfizer collaboration; and Sangamo’s need for substantial additional
funding to operate as a going concern. There can be no assurance
that Sangamo will earn any milestone or royalty payments under the
Pfizer agreement or obtain regulatory approvals for product
candidates arising from this agreement. Actual results may also
differ from those projected in forward-looking statements due to
risks and uncertainties that exist in Sangamo's and Pfizer’s
operations and businesses. These risks and uncertainties are
described more fully in Sangamo’s Securities and Exchange
Commission, or SEC, filings and reports, including in its Annual
Report on Form 10-K for the year ended December 31, 2023, as
supplemented by its Quarterly Report on Form 10-Q for the quarter
ended March 31, 2024, 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 release are made as of
July 24, 2024, and Sangamo undertakes no duty to update such
information except as required under applicable law.
i Ohmori T, Mizukami H, Ozawa K, et al. New approaches to gene
and cell therapy for hemophilia. J Thromb Haemost. 2015;13(Suppl
1): S133-142. ii Furlan R, Krishnan S, Vietri J. Patient and parent
preferences for characteristics of prophylactic treatment in
hemophilia. Patient Prefer Adherence. 2015; 9:1687-1694. iii
Centers for Disease Control and Prevention. What is hemophilia?
October 2023. Available at:
https://www.cdc.gov/hemophilia/about/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/hemophilia/facts.html.
Last accessed: July 2024. iv Pfrepper, Christian, et al.
"Emicizumab for the Treatment of Acquired Hemophilia A: Consensus
Recommendations from the GTH-AHA Working Group." Hämostaseologie
(2023). v Srivastava A, Santagostino E, Dougall A, et al. WFH
guidelines for the management of hemophilia, 3rd Edition; 2020.
Haemophilia, 26(S6), 1–158. vi Iorio A, Stonebraker JS, Chambost H,
et al. Establishing the Prevalence and Prevalence at Birth of
Hemophilia in Males: A Meta-analytic Approach Using National
Registries. Ann Intern Med 2019;171(8):540-546. vii WFH. World
Federation of Hemophilia Report on the Annual Global Survey 2022.
October 2023.
(https://www1.wfh.org/publications/files/pdf-2399.pdf). viii Brod
M, Bushnell DM, Neergaard JS, et al. Understanding treatment burden
in hemophilia: development and validation of the Hemophilia
Treatment Experience Measure (Hemo-TEM). J Patient Rep Outcomes.
2023;7(1):17.
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Investor Relations & Media Inquiries Louise Wilkie
ir@sangamo.com media@sangamo.com
Sangamo Therapeutics (NASDAQ:SGMO)
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