Giroctocogene fitelparvovec study meets primary
and key secondary objectives of superiority compared to
prophylaxis
Pfizer Inc. (NYSE: PFE) today announced positive topline results
from the Phase 3 AFFINE study (NCT04370054) evaluating
giroctocogene fitelparvovec, an investigational gene therapy for
the treatment of adults with moderately severe to severe hemophilia
A.
The AFFINE study 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 study, among all dosed participants, one participant
(1.3%) returned to prophylaxis post-infusion.
In the AFFINE study, giroctocogene fitelparvovec was generally
well tolerated. Transient 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,
providing bleed protection and reducing the need for routine
prophylaxis with intravenous (IV) infusions or
injections.1,2,3,4
“We are very pleased with these positive results from the Phase
3 AFFINE study demonstrating the safety and efficacy of our
one-time gene therapy candidate for people with hemophilia A,” said
James Rusnak, M.D., Ph.D., Senior Vice President, Chief Development
Officer, Internal Medicine and Infectious Diseases, Research and
Development, Pfizer. “We look forward to advancing this latest
innovation to help address the medical and treatment burden
associated with frequent and time-consuming IV infusions or
injections, building on Pfizer’s more than 40-year effort to
advance hemophilia treatment.”
In this Phase 3 study, eligible study participants were
initially enrolled in a lead-in study (NCT03587116) and upon
successful completion, were enrolled into the AFFINE study where
they received a one-time 3e13 vg/kg dose of giroctocogene
fitelparvovec by IV infusion. Participants in the AFFINE study were
screened with a validated assay designed to identify individuals
who test negative for neutralizing antibodies to the gene therapy
vector. Clinical study 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 study.
Analyses of the full Phase 3 dataset from the AFFINE study 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 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. BEQVEZ is also
approved in Canada and is awaiting a decision from the European
Medicines Agency (EMA) following a positive opinion from the EMA’s
Committee for Medicinal Products for Human Use in May 2024.
Additionally, regulatory submissions for marstacimab are currently
under review by the FDA and the EMA. Marstacimab is a potential
novel subcutaneous therapy being studied for the treatment of
people with hemophilia A and B with and without inhibitors. Pfizer
announced the acceptance of the regulatory filings for the without
inhibitors cohort in December 2023.
About the AFFINE Study
The Phase 3 AFFINE (NCT04370054) study is an open-label,
multicenter, single-arm study 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. Study 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 annualized bleeding rate
(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 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.5
Hemophilia A occurs in approximately 25 in every 100,000 male
births worldwide.6 Approximately 55-75% of males with hemophilia A
have a moderate to severe form of the disease.7 For people who live
with hemophilia A, there is an increased risk of spontaneous
bleeding as well as bleeding following injuries or surgery.5 It is
a lifelong disease that requires constant monitoring and
therapy.8
About Pfizer: Breakthroughs that Change Patients’
Lives
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value
in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
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Disclosure Notice
The information contained in this release is as of July 24,
2024. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new
information or future events or developments.
This release contains forward-looking information about
giroctocogene fitelparvovec, an investigational gene therapy for
hemophilia A, including its potential benefits and topline results
from a Phase 3 study, and Pfizer’s hemophilia portfolio, that
involve substantial risks and uncertainties that could cause actual
results to differ materially from those expressed or implied by
such statements. Risks and uncertainties include, among other
things, the uncertainties inherent in research and development,
including the ability to meet anticipated clinical endpoints,
commencement and/or completion dates for our clinical trials,
regulatory submission dates, regulatory approval dates and/or
launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data,
including results from the AFFINE study and the long-term follow-up
study; the risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when drug
applications may be filed in any jurisdictions for any potential
indication for giroctocogene fitelparvovec or any other hemophilia
product candidates; whether and when any such applications that may
be pending or filed may be approved by regulatory authorities,
which will depend on myriad factors, including making a
determination as to whether the product's benefits outweigh its
known risks and determination of the product's efficacy and, if
approved, whether giroctocogene fitelparvovec or any such other
product candidates will be commercially successful; decisions by
regulatory authorities impacting labeling, manufacturing processes,
safety and/or other matters that could affect the availability or
commercial potential of giroctocogene fitelparvovec or any such
other product candidates; uncertainties regarding the commercial
success of Pfizer’s hemophilia products; uncertainties regarding
the impact of COVID-19 on our business, operations and financial
results; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2023, and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
_________________________
1 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.
2 Furlan R, Krishnan S, Vietri J. Patient
and parent preferences for characteristics of prophylactic
treatment in hemophilia. Patient Prefer Adherence. 2015;
9:1687-1694.
3 Centers for Disease Control and
Prevention. What is hemophilia? October 2023. Available at:
https://www.cdc.gov/ncbddd/hemophilia/facts.html#:~:text=Hemophilia%20is%20usually%20an%20inherited,can%20help%20to%20stop%20bleeding.
Last accessed: July 2024.
4 Pfrepper, Christian, et al. "Emicizumab
for the Treatment of Acquired Hemophilia A: Consensus
Recommendations from the GTH-AHA Working Group." Hämostaseologie
(2023).
5 Srivastava A, Santagostino E, Dougall A,
et al. WFH guidelines for the management of hemophilia, 3rd
Edition; 2020. Haemophilia, 26(S6), 1–158.
6 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.
7 WFH. World Federation of Hemophilia
Report on the Annual Global Survey 2022. October 2023.
(https://www1.wfh.org/publications/files/pdf-2399.pdf).
8 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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