Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy
company dedicated to challenging the inevitability of genetic
disease, today announced new three-year follow-up data from the
continuing Phase 3 trial of LUXTURNA™ (voretigene neparvovec), an
investigational, potential one-time gene therapy for the treatment
of patients with vision loss due to confirmed
biallelic RPE65-mediated inherited retinal disease (IRD).
These data were presented at the American Academy of Ophthalmology
(AAO) Retina Subspecialty Day by Albert M. Maguire, M.D., a
principal investigator of the Phase 3 clinical trial, professor of
ophthalmology at the Scheie Eye Institute at the
University of Pennsylvania’s Perelman School of
Medicine and attending physician in the Division of
Pediatric Ophthalmology at Children's
Hospital of Philadelphia.
“These data provide additional support information on the
efficacy, durability and safety of investigational LUXTURNA,
showing no statistically significant change in the primary endpoint
from the initial gain in functional vision at the three-year time
point for the original intervention group and at the two-year time
point for the original control group after crossover,”
said Katherine High, M.D., president and head of Research and
Development at Spark Therapeutics. “We believe the data from these
participants further support the positive benefit-risk profile of
investigational LUXTURNA for patients with vision loss due to
confirmed biallelic RPE65-mediated IRD.”
Functional vision is considered a key component in a person’s
ability to perform daily living tasks and can be assessed through
orientation and mobility testing and other measurements.
Three years after the one-time administration of investigational
LUXTURNA to both eyes, the cohort of 20 participants in the
modified intent-to-treat (mITT) intervention group maintained the
average improvement demonstrated at one year, as measured by
multi-luminance mobility test (MLMT) score change, the primary
endpoint, and full-field light sensitivity threshold (FST) testing,
a secondary endpoint. The mean MLMT improvement measured 1.8 lux
levels at three years, compared to 1.9 lux levels at one year. The
more than 100-fold average improvement in FST testing observed in
the intervention group at one year similarly was maintained through
at least three years. Additionally, the increase in visual acuity
(VA) averaged over both eyes, a secondary endpoint which was not
statistically significant at one year, has been stable for at least
three years for participants in the intervention cohort, at an
eight-letter improvement using standardized AV testing.
The mean change from baseline in Goldmann III4e test stimulus, a
pre-specified exploratory measure of visual field (VF), was 282.2
sum total degrees averaged over both eyes for participants in the
intervention group at the three-year time point, compared to a mean
change of 302.1 sum total degrees at one year.
Likewise, all participants in the control group (n=9), who after
one year of undergoing observation with the same retinal and visual
function testing as the original intervention group elected to
cross over and receive LUXTURNA in both eyes, maintained the same
mean MLMT score change of 2.1 lux levels one year following the
one-time injection through two years after administration. The more
than 100-fold average improvement in FST testing observed in the
crossover group at one year similarly was maintained through at
least two years. Similarly, in the crossover group, the
increase in VA averaged over both eyes, was not statistically
significant at one year, but has remained improved compared to
baseline for at least two years.
The mean change from baseline in Goldmann VF was 182.6 sum total
degrees averaged over both eyes for participants in the crossover
group at the two-year time point, compared to a mean change of
194.3 sum total degrees at one year.
No new serious adverse events (SAEs) associated with LUXTURNA or
deleterious immune responses were observed. Most ocular adverse
events (AEs) were mild in severity, with the most common being
cataract, elevated intraocular pressure, retinal deposits and
retinal tears. One participant in the crossover group experienced
an SAE related to the surgical procedure in which there was foveal
thinning and a sustained reduction in VA. Three participants in the
intervention group had SAEs unrelated to study participation.
LUXTURNA is under Priority Review with the U.S. Food and Drug
Administration (FDA), with an assigned Prescription Drug User Fee
Act (PDUFA) date of Jan. 12, 2018. In October 2017, FDA’s Cellular,
Tissue and Gene Therapies Advisory Committee unanimously
recommended (16-0) approval of LUXTURNA. The advisory committee’s
recommendation is non-binding, but FDA generally considers such
recommendations when reviewing a Biologics License Application
(BLA). LUXTURNA has received orphan drug, breakthrough therapy and
rare pediatric disease designations from FDA.
In August 2017, Spark Therapeutics’ Marketing Authorization
Application (MAA) for LUXTURNA was validated by European Medicines
Agency (EMA). LUXTURNA also has received orphan product
designations from EMA.
Clinical Trial Overview of
LUXTURNA™ (voretigene
neparvovec)The safety and efficacy of LUXTURNA were
assessed in two open-label Phase 1 trials, which continue to follow
participants who received LUXTURNA between 2007 and 2012, and one
open-label, randomized, controlled Phase 3 trial. The LUXTURNA
clinical program overall includes up to four years of efficacy data
from a single dose. The overall safety profile has not
changed over the period of observation, and has been previously
reported (The Lancet 2016; The Lancet 2017).
Following the one-year control period of the Phase 3 study, all
control participants elected to cross over and received LUXTURNA;
long-term safety and efficacy continue to be assessed in the Phase
3 participants who received LUXTURNA between 2013 and 2015. The
clinical trial program included 41 participants with vision loss
ranging from mild to advanced, and included individuals from age
four to 44 years at the time of first administration. Confirmed
biallelic RPE65 mutations and the presence of sufficient viable
retinal cells were established in all participants.
LUXTURNA Phase 3 clinical trial data, including data from the
intent-to-treat population of all randomized participants through
the one-year time point, were published in The Lancet. Results
included in the BLA submission 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) score change (difference of 1.6; 95% CI, 0.72, 2.41;
p=0.001). In addition, participants who received LUXTURNA showed a
marked difference compared to control participants across the first
two secondary endpoints: full-field light sensitivity threshold
(FST) testing averaged over both eyes (p=0.001) and the mobility
test score change for the first injected eye (p=0.001). A third
secondary endpoint, the change in visual acuity (VA) averaged over
both eyes, was not statistically significant between intervention
and control participants (p=0.17).
On average, participants in the original Phase 3 intervention
group maintained functional gains observed by the day-30 visit
through their last annual follow-up visit, as measured by MLMT and
FST, with observation ongoing. Average improvement in FST testing
observed in the original intervention group at one year was more
than 100-fold (or greater than two log units).
In continuation of the trial to include crossover of the control
group to receive LUXTURNA, 93 percent (27 of 29) of all treated
Phase 3 trial participants saw a gain of functional vision as
assessed by bilateral MLMT over the follow-up period of at least
one year from administration of LUXTURNA to each eye. Additionally,
72 percent (21 of 29) of all Phase 3 trial participants receiving
LUXTURNA successfully completed MLMT at the lowest light level
evaluated (1 lux) at one year.
Data from a cohort of the Phase 1 clinical trial, in which
investigational LUXTURNA was administered to the contralateral, or
second previously uninjected eye, showed mean improvements in
functional vision and visual function. This cohort of participants
(n=11) received the same dose of LUXTURNA that was administered in
the Phase 3 trial and would have met the Phase 3 eligibility
criteria. See the publication of the three-year Phase 1 data in The
Lancet (2016).
Two ocular SAEs were reported in the clinical program. There was
one SAE related to the surgical procedure in one eye of a Phase 3
participant, in which there was foveal thinning and a sustained
reduction in VA. One additional ocular SAE was reported in one eye
of a Phase 1 participant in which the treatment for bacterial
endophthalmitis led to elevated intraocular pressure and subsequent
optic atrophy. There were three non-serious AEs of retinal deposits
(subretinal precipitate) in three participants (three eyes) that
were considered to be related to LUXTURNA. All three of these
events were mild in intensity, transient in nature and resolved
without consequences. No deleterious immune responses have been
observed. The most common adverse reactions related to LUXTURNA
reported in 10 percent or greater of the combined Phase 1 and Phase
3 trial participants included conjunctival hyperemia, cataract,
increased intraocular pressure and retinal tear.
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,
often disproportionally affecting children and young adults. 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 IRD due
to biallelic RPE65 gene mutations.
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 Therapeutics At Spark Therapeutics,
a fully integrated company committed to discovering, developing and
delivering gene therapies, we challenge the inevitability of
genetic diseases, including blindness, hemophilia and
neurodegenerative diseases. We have successfully applied our
technology directed to the retina and liver, and currently have
four programs in clinical trials or under regulatory review,
including the first potential gene therapy for a genetic disease in
the United States and product candidates that have shown promising
early results in patients with hemophilia. At Spark, we see
the path to a world where no life is limited by genetic disease.
For more information, visit www.sparktx.com, and follow us on
Twitter and LinkedIn.
Cautionary note on forward-looking statements
This release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements regarding the company's product candidate
LUXTURNA™ (voretigene neparvovec). The words ‘‘anticipate,’’
‘‘believe,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’
‘‘predict,’’ ‘‘will,’’ ‘‘would,’’ ‘‘could,’’ ‘‘should,’’
‘‘continue’’ and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. We may not actually
achieve the plans, intentions or expectations disclosed in our
forward-looking statements, and you should not place undue reliance
on our forward-looking statements. 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 or MAA submitted for LUXTURNA may not be approved
by FDA or EMA, respectively; (ii) the data from our Phase 3
clinical trial of LUXTURNA may not support US labeling for all
biallelic RPE65 mutations other than Leber congenital amaurosis
(LCA) or retinitis pigmentosa (RP); (iii) the improvements in
functional vision demonstrated by LUXTURNA in our clinical trials
may not be sustained over extended periods of time; and (iv) any
one or more of our product candidates in preclinical or clinical
development will not successfully be developed and commercialized.
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 |
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Media Contact:Monique da
SilvaMonique.dasilva@sparktx.com (215) 282-7470 |
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