Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy
company dedicated to challenging the inevitability of genetic
disease, today announced The Lancet, a highly ranked peer-reviewed
journal, has published Phase 3 clinical trial data of voretigene
neparvovec, an investigational, potential one-time gene therapy
candidate for the treatment of patients with vision loss due to
confirmed biallelic RPE65-mediated inherited retinal disease (IRD).
In the trial, investigational voretigene neparvovec improved
functional vision, light sensitivity and visual field in study
participants with RPE65-mediated IRD. A natural history study has
shown that people with this IRD eventually progress to complete
blindness.
Functional vision refers to a person's ability to perform, on
his or her own, visually dependent activities of daily living. This
is typically measured per person rather than per eye, and may be
thought of as the performance output of various aspects of visual
function. Visual function is measured by tests performed on each
eye individually, such as light sensitivity, visual acuity
(determined by the smallest letters one can read on a standardized
eye chart from a specified distance), and visual field (which
refers to the area in which objects can be detected in the
periphery while the eye is focused on a central point). This
clinical trial evaluated both functional vision and various aspects
of visual function.
The publication presents the results of the Phase 3 trial,
including the intent-to-treat population of all randomized
subjects, through the one-year timepoint. Results showed a
statistically significant and clinically meaningful difference
between intervention (n=21) and control participants (n=10) at one
year, per the clinical trial’s primary endpoint, mean bilateral
multi-luminance mobility testing (MLMT) change score (difference of
1.6; 95% CI, 0.72, 2.41; p=0.0013). Participants maintained
functional gains observed 30 days post-administration at the
one-year primary endpoint. MLMT evaluates functional vision by
documenting the participants' ability to navigate a mobility course
under a variety of specified light levels ranging from one lux
(equivalent to, for example, a moonless summer night) to 400 lux
(equivalent to, for example, an office environment).
Improvements seen in MLMT were accompanied by statistically
significant improvements in two secondary endpoints, including
full-field light sensitivity threshold (FST) testing averaged over
both eyes (p=0.0004). A third secondary endpoint, the change in
visual acuity averaged over both eyes, was not statistically
significant between intervention and control participants (p=0.17).
An additional protocol-specified endpoint using the Goldmann III4e
test stimulus to measure the visual field area of the original
intervention group showed significant improvement (p=0.0059),
nearly doubling at year one, while a slight decrease was observed
in the control group over the same time period.
No serious adverse events (SAEs) associated with voretigene
neparvovec or deleterious immune responses were observed. Most
ocular events were mild in severity with the most common ocular
adverse events (AEs) being transient mild ocular inflammation,
transient elevated intraocular pressure, cataracts and
intraoperative retinal tears. Two participants in the intervention
group, one with a pre-existing complex seizure disorder and another
who experienced complications from oral surgery, had SAEs unrelated
to study participation.
Please refer to the paper, “Efficacy and safety of voretigene
neparvovec (AAV2-hRPE65v2) in subjects with RPE65-mediated
inherited retinal dystrophy: a randomised, controlled, open-label
Phase 3 trial,” for additional results from the pivotal phase of
this study.
“These data from the first randomized, controlled Phase 3 gene
therapy clinical trial ever conducted for a genetic disease are
supportive of the potential role that investigational voretigene
neparvovec may play in the treatment of IRD caused by biallelic
mutations in the RPE65 gene,” said Stephen R. Russell, M.D.,
of the Stephen A. Wynn Institute for Vision Research at the
University of Iowa, who was a principal investigator for the Phase
3 trial. “The data show clinically meaningful and statistically
significant improvements in ability to navigate independently in
low to moderate light conditions, as well as marked improvements in
full-field light sensitivity and peripheral vision. As a treating
physician, it’s exciting to see these types of results in a disease
area where no approved pharmacologic treatment options currently
exist.”
In May 2017, Spark Therapeutics completed the rolling submission
of a Biologics License Application (BLA) with the U.S. Food and
Drug Administration (FDA) for voretigene neparvovec for the
treatment of patients with vision loss due to confirmed biallelic
RPE65 mutation-associated retinal disease. FDA has 60 days to
review the submission to determine if it is complete. If deemed
complete, the application will be considered filed and the review
period will begin. Voretigene neparvovec has received breakthrough
therapy designation from FDA, given to drugs when preliminary
clinical evidence indicates that the drug may demonstrate
substantial improvement over existing therapies based on one or
more clinically significant endpoints, and orphan product
designations from FDA and European Medicines Agency (EMA), granted
to drugs that treat a rare disease or condition.
About RPE65-mediated
Inherited Retinal Disease (IRD)Inherited retinal diseases
(also known as inherited retinal dystrophies) are a group of rare
blinding conditions caused by one of more than 220 different genes.
People living with IRD due to biallelic RPE65 gene mutations often
experience night blindness (nyctalopia) due to decreased light
sensitivity in childhood or early adulthood and involuntary
back-and-forth eye movements (nystagmus). As the disease
progresses, individuals may experience loss in their peripheral
vision, developing tunnel vision, and eventually, they may lose
their central vision as well, resulting in total blindness.
Independent navigation becomes severely limited, and
vision-dependent activities of daily living are impaired. There are
currently no approved pharmacologic treatment options for this
disease.
About Gene TherapyGene therapy is an
investigational approach to treat or prevent genetic disease by
seeking to augment, replace or suppress one or more mutated genes
with functional copies. It addresses the root cause of an inherited
disease by enabling the body to produce a protein or proteins
necessary to restore health or to stop making a harmful protein or
proteins, with the potential of bringing back function in the
diseased cells and slowing disease progression. To deliver the
functional gene into the cell, a vector is used to transport the
desired gene and is delivered either intravenously (IV) or injected
into specific tissue. The goal is to enable, through the one-time
administration of gene therapy, a lasting therapeutic effect.
About Spark TherapeuticsSpark Therapeutics, a
fully integrated company, strives to challenge the inevitability of
genetic disease by discovering, developing, and delivering gene
therapies that address inherited retinal diseases (IRDs),
neurodegenerative diseases, as well as diseases that can be
addressed by targeting the liver. Our validated platform
successfully has delivered proof-of-concept data with
investigational gene therapies in the retina and liver. Our most
advanced investigational candidate, voretigene neparvovec, in
development for the treatment of biallelic RPE65-mediated IRD, has
received orphan designations in the U.S. and European Union, and
breakthrough therapy designation in the U.S. The pipeline also
includes SPK-7001 in a Phase 1/2 trial for choroideremia, and two
hemophilia development programs: SPK-9001 (which also has received
both breakthrough therapy and orphan product designations by the
FDA, and access to the PRIority MEdicines (PRIME) Program by the
EMA) in a Phase 1/2 trial for hemophilia B being developed in
collaboration with Pfizer, and SPK-8011, in a Phase 1/2 trial for
hemophilia A to which Spark Therapeutics retains global
commercialization rights. To learn more about us and our growing
pipeline, visit www.sparktx.com.
Cautionary note on forward-looking
statementsThis release contains "forward-looking
statements" within the meaning of the Private Securities Litigation
Reform Act of 1995, including statements regarding the
company's product candidates, including voretigene neparvovec,
SPK-7001, SPK-9001 and SPK-8011. Any forward-looking statements are
based on management's current expectations of future events and are
subject to a number of risks and uncertainties that could cause
actual results to differ materially and adversely from those set
forth in, or implied by, such forward-looking statements. These
risks and uncertainties include, but are not limited to, the risk
that: (i) our BLA submitted to the FDA may not be accepted, or, if
accepted, may not be approved; (ii) the data from our Phase 3
clinical trial of voretigene neparvovec may not support labeling
for all biallelic RPE65 mutations other than Leber congenital
amaurosis (LCA); and (iii) the improvements in functional vision
demonstrated by voretigene neparvovec in our clinical trials may
not be sustained over extended periods of time. For a discussion of
other risks and uncertainties, and other important factors, any of
which could cause our actual results to differ from those contained
in the forward-looking statements, see the "Risk Factors" section,
as well as discussions of potential risks, uncertainties and other
important factors, in our Annual Report on Form 10-K, our Quarterly
Reports on Form 10-Q and other filings we make with
the Securities and Exchange Commission. All information in
this press release is as of the date of the release, and Spark
undertakes no duty to update this information unless required by
law.
Investor Contact:
Ryan Asay
Ryan.asay@sparktx.com
(215) 239-6424
Media Contact:
Monique da Silva
Monique.dasilva@sparktx.com
(215) 282-7470
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