LUXTURNA is first gene therapy for a genetic disease, first and only
pharmacologic treatment for an inherited retinal disease (IRD) and first
adeno-associated virus (AAV) vector gene therapy approved in U.S.
Children and adults living with IRD caused by biallelic RPE65 gene mutations
nearly all progress to complete blindness
Spark Therapeutics to offer comprehensive patient support services for eligible
patients in U.S.; will share details on access and price in early January
PHILADELPHIA, Dec. 19, 2017 (GLOBE NEWSWIRE) -- Spark Therapeutics
(NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging
the inevitability of genetic disease, announced today that the U.S. Food and
Drug Administration (FDA) has approved LUXTURNA (voretigene neparvovec-rzyl),
a one-time gene therapy product indicated for the treatment of patients with
confirmed biallelic RPE65 mutation-associated retinal dystrophy. LUXTURNA
should only be administered to patients with mutations on both copies of the
RPE65 gene who have sufficient viable retinal cells as determined by their
treating physicians.
LUXTURNA is the first FDA-approved gene therapy for a genetic disease, the
first and only pharmacologic treatment for an inherited retinal disease (IRD)
and the first adeno-associated virus (AAV) vector gene therapy approved in the
U.S.
"Today's landmark approval of LUXTURNA is a moment decades in the making for
the field of gene therapy, the inherited retinal disease (IRD) community, and
most importantly, patients with biallelic RPE65mutation associated retinal
dystrophy who now have the option to seek treatment," said Jeffrey D. Marrazzo,
chief executive officer at Spark Therapeutics. "This one-time gene therapy for
an inherited disease represents a first-of-its-kind breakthrough that may lay
the groundwork for the development of gene therapies for other conditions that
are not adequately addressed today. We offer our sincere gratitude to the
patients and their families as well as the expert investigators who continue to
participate in LUXTURNA's clinical development program."
"FDA approval of LUXTURNA represents a true paradigm shift for physicians
caring for patients with hereditary retinal disease caused by biallelic RPE65
mutations, who up until now have had no pharmacologic treatment options," said
Alex V. Levin, M.D., MHSc, pediatric ophthalmologist and chief of the Wills Eye
Pediatric Ophthalmology and Ocular Genetics Service in Philadelphia. "Now is
the time for patients who have hereditary retinal disease, but lack a confirmed
genetic diagnosis, to undergo genetic testing to determine, where appropriate,
if mutations in the RPE65 gene are responsible for their disease, and whether
LUXTURNA may be an appropriate treatment option."
The U.S. Prescribing Information for LUXTURNA includes the following Warnings
and Precautions: endophthalmitis; permanent decline in visual acuity; retinal
abnormalities; increased intraocular pressure; expansion of intraocular air
bubbles; and cataract. LUXTURNA is not recommended for patients younger than 12
months of age because the retina is still growing, which may affect how
LUXTURNA works. LUXTURNA is administered by subretinal injection to each eye on
separate days within a close interval, but no fewer than 6 days apart. Please
see the Indication and Important Safety Information section below for more
information regarding risks associated with LUXTURNA.
LUXTURNA will be manufactured at Spark Therapeutics' manufacturing facility
located in West Philadelphia, which is the first licensed manufacturing
facility in the U.S. for a gene therapy treating an inherited disease. The gene
therapy will be administered at selected treatment centers in the U.S. by
leading retinal surgeons, who will receive surgical training provided by Spark
Therapeutics on the administration procedure. LUXTURNA is expected to be
available for administration in these treatment centers late in the first
quarter of 2018. Spark Therapeutics is committed to ensuring eligible patients
have access to LUXTURNA. More details on the company's patient support
programs, its commitment to access, and the price of the product will be shared
in early January.
"During the more than 12 years of innovative research with dedicated
collaborators near and far, I've witnessed the dramatic improvement in vision
in many patients who would have otherwise lost their sight," said Jean Bennett,
the F.M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at
the University of Pennsylvania and Penn's Scheie Eye Institute. "I believe that
the success of the LUXTURNA clinical development program will pave the way for
the development of other gene therapies, that may help the millions of patients
with genetic diseases who currently have limited or no treatment options."
"This approval is a watershed milestone," said Benjamin Yerxa, Ph.D., chief
executive officer at the Foundation Fighting Blindness (FFB), a nonprofit
organization focused on research for preventing and treating blindness caused
by IRDs. "For people with an inherited retinal disease and for other patient
communities, this decision may create important momentum for investigational
gene therapies. The Foundation is very pleased that our early investments in
research have helped lead to the approval of LUXTURNA. And we encourage
patients to get genetic testing so they can help advance the research and
possibly benefit from this treatment or other gene treatments as they emerge."
LUXTURNA was approved by FDA under Priority Review and previously received
orphan drug and breakthrough therapy designations from FDA. With the approval
of LUXTURNA, FDA will issue to Spark Therapeutics a Rare Pediatric Disease
Priority Review Voucher for a Priority Review of a subsequent marketing
application for a different product. Spark Therapeutics' Marketing
Authorization Application (MAA) for LUXTURNA is currently under review with the
European Medicines Agency (EMA). LUXTURNA also has received orphan product
designations from EMA.
Genetic Testing and Obtaining a Genetic Diagnosis for Biallelic RPE65
Mutation-associated Retinal Dystrophy
A genetic test is the only way to verify the gene mutation(s) that is the
underlying cause of an inherited retinal disease (IRD), including those
associated with biallelic RPE65 mutations.
For people with IRDs, Spark Therapeutics will offer access to genetic testing
designed to identify biallelic RPE65 mutations. More information about the
program and eligibility requirements will be available at www.luxturna.com.
Genetic testing is also available through a variety of other channels,
including as a covered service through a patient's insurance, through
non-profit organizations, as well as through various commercial labs.
Patient Support for Accessing LUXTURNA
Spark Therapeutics is committed to helping ensure that appropriate patients in
the U.S. with a confirmed genetic diagnosis of biallelic RPE65
mutation-associated retinal dystrophy have access to LUXTURNA. Spark has
established Spark Therapeutics Generation Patient Services(SM) to support
appropriate patients, their families and providers in the U.S. through the
LUXTURNA treatment experience. The team at Spark Therapeutics Generation
Patient Services will assist eligible and enrolled patients navigate the
insurance process and provide options to support travel and logistics to and
from treatment centers.
For patients who are underinsured or are insured through government programs
like Medicare and Medicaid, Spark plans to support independent Patient
Assistance Programs that may help cover their drug and treatment costs.
More information will be available for patients and healthcare providers in the
U.S. at www.mysparkgeneration.com or by calling 1-833-SPARK-PS (833-772-7577).
Indication and Important Safety Information
LUXTURNA (voretigene neparvovec-rzyl) is an adeno-associated virus vector-based
gene therapy indicated for the treatment of patients with confirmed biallelic
RPE65 mutation-associated retinal dystrophy.
Patients must have viable retinal cells as determined by the treating
physicians.
Warnings and Precautions
· Endophthalmitis may occur following any intraocular surgical
procedure or injection. Use proper aseptic injection technique when
administering LUXTURNA, and monitor for and advise patients to report any signs
or symptoms of infection or inflammation to permit early treatment of any
infection.
· Permanent decline in visual acuity may occur following subretinal
injection of LUXTURNA. Monitor patients for visual disturbances.
· Retinal abnormalities may occur during or following the subretinal
injection of LUXTURNA, including macular holes, foveal thinning, loss of foveal
function, foveal dehiscence, and retinal hemorrhage. Monitor and manage these
retinal abnormalities appropriately. Do not administer LUXTURNA in the
immediate vicinity of the fovea. Retinal abnormalities may occur during or
following vitrectomy, including retinal tears, epiretinal membrane, or retinal
detachment. Monitor patients during and following the injection to permit early
treatment of these retinal abnormalities. Advise patients to report any signs
or symptoms of retinal tears and/or detachment without delay.
· Increased intraocular pressure may occur after subretinal injection
of LUXTURNA. Monitor and manage intraocular pressure appropriately.
· Expansion of intraocular air bubbles Instruct patients to avoid air
travel, travel to high elevations or scuba diving until the air bubble formed
following administration of LUXTURNA has completely dissipated from the eye. It
may take one week or more following injection for the air bubble to dissipate.
A change in altitude while the air bubble is still present can result in
irreversible vision loss. Verify the dissipation of the air bubble through
ophthalmic examination.
· Cataract Subretinal injection of LUXTURNA, especially vitrectomy
surgery, is associated with an increased incidence of cataract development
and/or progression.
Adverse Reactions
· In clinical studies, ocular adverse reactions occurred in 66% of
study participants (57% of injected eyes), and may have been related to
LUXTURNA, the subretinal injection procedure, the concomitant use of
corticosteroids, or a combination of these procedures and products.
· The most common adverse reactions (incidence = 5% of study
participants) were conjunctival hyperemia (22%), cataract (20%), increased
intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal
stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation
(5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the
surface of the macula) (5%).
Immunogenicity
Immune reactions and extra-ocular exposure to LUXTURNA in clinical studies were
mild. No clinically significant cytotoxic T-cell response to either AAV2 or
RPE65 has been observed. Study participants received systemic corticosteroids
before and after subretinal injection of LUXTURNA to each eye, which may have
decreased the potential immune reaction to either AAV2 or RPE65.
Pediatric Use
Treatment with LUXTURNA is not recommended for patients younger than 12 months
of age, because the retinal cells are still undergoing cell proliferation, and
LUXTURNA would potentially be diluted or lost during the cell proliferation.
The safety and efficacy of LUXTURNA have been established in pediatric
patients. There were no significant differences in safety between the different
age subgroups.
Please see the full U.S. Prescribing Information for LUXTURNA here.
Clinical Trial Overview of LUXTURNA (voretigene neparvovec-rzyl)
The safety and efficacy of LUXTURNA were assessed in one open-label,
dose-exploration Phase 1 safety study (n=12) and one open-label, randomized,
controlled Phase 3 efficacy and safety study (n=31) in pediatric and adult
participants (range 4 to 44 years) with biallelic RPE65 mutation-associated
retinal dystrophy and sufficient viable retinal cells.
Of the 31 participants enrolled in the Phase 3 study, 21 were randomized to
receive subretinal injection of LUXTURNA and 10 were randomized to the control
(non-intervention) group. One participant in the intervention group
discontinued from the study prior to treatment and one participant in the
control group withdrew consent and was discontinued from the study. All nine
participants randomized to the control group elected to crossover and receive
LUXTURNA after one year of observation. All participants in these studies
continue to be followed for long-term safety and efficacy. LUXTURNA Phase 3
clinical trial data, including data from the intervention group of all
randomized participants through the one-year time point has been previously
reported in (The Lancet).
The efficacy of LUXTURNA in the Phase 3 study was established based on the
multi-luminance mobility test (MLMT) score change from baseline to one year.
MLMT was designed to measure changes in functional vision as assessed by the
ability of a participant to navigate a course accurately and at a reasonable
pace at seven different levels of illumination, ranging from 400 lux
(corresponding to a brightly lit office) to one lux (corresponding to a
moonless summer night). Each light level was assigned a score ranging from zero
to six, with a higher score indicating that a participant could pass MLMT at a
lower light level. A score of negative one was assigned to participants who
could not pass MLMT at a light level of 400 lux. MLMT score change was defined
as the difference between the score at baseline and the score at one year with
a positive score change indicating that a participant was able to complete MLMT
at a lower light level. Additional clinical outcomes included white light
full-field light sensitivity threshold (FST) testing and visual acuity.
LUXTURNA Phase 3 clinical study results showed a statistically significant
difference between the intervention group (n=21) and control participants
(n=10) at one year in median bilateral MLMT score change (intervention minus
control group difference of 2; p=0.001) and median first-treated eye MLMT score
change (intervention minus control group difference of 2; p=0.003). After
crossing over to receive LUXTURNA, participants in the control group showed a
similar response to those in the intervention group. The median bilateral MLMT
score change of two was observed for the intervention group at the 30-day
timepoint. This change score has been sustained for at least three years for
the original intervention group and at least two years in the crossover group
in the Phase 3 clinical study. In addition, participants who received LUXTURNA
showed a statistically significant improvement from baseline to one year in
white light FST in the intervention group compared to the control group. The
change in visual acuity from baseline to one year was not significantly
different between the intervention and control participants.
The U.S. Prescribing Information for LUXTURNA includes the following Warnings
and Precautions: endophthalmitis; permanent decline in visual acuity; retinal
abnormalities; increased intraocular pressure; expansion of intraocular air
bubbles; and cataract. The most common adverse reactions (incidence = 5%) were
conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear,
dellen (thinning of the corneal stroma), macular hole, subretinal deposits, eye
inflammation, eye irritation, eye pain and maculopathy (wrinkling on the
surface of the macula).
About RPE65 Mutation-associated 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. Based on
Spark Therapeutics' assessment of available epidemiology data, the prevalent
population in the U.S., Europe and select additional markets in the Americas
and Asia/Pacific is up to approximately 6,000 individuals, in total, with
biallelic RPE65 mutations. It is estimated that between 1,000-2,000 people in
the U.S. have vision loss due to these biallelic RPE65 mutations. In addition,
an expected 10-20 new patients a year are born with RPE65 mutations in the U.S.
People living with IRD due to biallelic RPE65 gene mutations nearly all
progress to complete blindness. They 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 Therapy
Gene therapy is an 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/or 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 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 in the first FDA-approved
gene therapy in the U.S. for a genetic disease, and currently have three
programs in clinical trials, including 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 LUXTURNA (voretigene neparvovec-rzyl). 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 MAA submitted for LUXTURNA may not be approved by EMA; (ii)
the data from our Phase 3 clinical trial of LUXTURNA may not support EU
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 Relations Contact:
Ryan Asay
Ryan.asay@sparktx.com
(215) 239-6424
Media Contact:
Monique da Silva
communications@sparktx.com
(215) 282-7470
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