LUXTURNA is first gene therapy for a genetic
disease approved in both the U.S. and EU
Spark Therapeutics (NASDAQ:ONCE), a fully integrated, commercial
gene therapy company dedicated to challenging the inevitability of
genetic disease, today announced that the European Commission has
granted marketing authorization for LUXTURNA® (voretigene
neparvovec), a one-time gene therapy for the treatment of adult and
pediatric patients with vision loss due to inherited retinal
dystrophy caused by confirmed biallelic RPE65 mutations and who
have sufficient viable retinal cells. RPE65-mediated inherited
retinal disease (IRD) is a progressive condition leading to total
blindness in most patients. This authorization is valid in all
28-member states of the EU, as well as Iceland, Liechtenstein and
Norway. LUXTURNA is the first gene therapy for a genetic disease
that has received regulatory approval in both the U.S. and EU.
“The historic approval of LUXTURNA in Europe furthers our
mission to challenge the inevitability of genetic disease around
the world. Following the launch of LUXTURNA in the United States
earlier this year, this decision makes LUXTURNA the first gene
therapy for a genetic disease approved in both the U.S. and EU, a
promising milestone for the many people living with genetic disease
around the world,” said Ron Philip, chief commercial officer at
Spark Therapeutics. “Having worked closely with the global IRD
community on the development of LUXTURNA, we are proud to be able
to share the first gene therapy treatment option for an inherited
retinal disease (IRD) with appropriate patients in Europe, in
collaboration with Novartis.”
In January 2018, Spark Therapeutics entered into a licensing
agreement with Novartis to commercialize LUXTURNA when approved in
Europe and all other markets outside the U.S. Under the licensing
agreement, Novartis has exclusive rights to pursue development,
registration and commercialization in all countries outside the
U.S. Upon the transfer of the marketing authorization from Spark
Therapeutics to Novartis, Novartis can commercialize LUXTURNA in
the EU/European Economic Area (EEA). Spark Therapeutics entered
into a separate agreement with Novartis to manufacture and supply
LUXTURNA to Novartis.
“Today’s approval is momentous for patients given that there
have been no pharmacological treatment options to date,” said
Christina Fasser, president of Retina International, an umbrella
organization of more than 43 patient organizations worldwide
promoting research to find treatments for inherited retinal
degenerative diseases. “Access to this treatment has the potential
to reduce the substantial physical, emotional and financial burden
this disease has on patients and their families.”
In September 2018, the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines
Agency (EMA) adopted a positive opinion recommending approval
of LUXTURNA. This decision was based on data from a Phase 1
clinical trial, its follow-up trial and a Phase 3 trial that
together enrolled 43 participants with inherited retinal disease
caused by mutations in both copies of the RPE65 gene. The Phase 3
trial was the first randomized, controlled gene therapy trial for a
genetic disease. LUXTURNA is designated as an orphan medicinal
product for the treatment of inherited retinal dystrophies.
LUXTURNA was approved by the U.S. Food & Drug Administration
(FDA) in December 2017.
Clinical Trial Overview of
LUXTURNA® (voretigene neparvovec)The
safety and efficacy of LUXTURNA were assessed in one open-label,
dose-exploration Phase 1 safety study (n=12), a second open-label
Phase 1 follow-on study to assess the safety of injection of the
contralateral eye (n=11) and an 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 disease 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 cross over to receive
LUXTURNA after one year of observation. All participants in these
studies planned 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, have been previously reported in The
Lancet.
The efficacy of LUXTURNA in the Phase 3 study was established
based on the binocular 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, both
averaged over both eyes.
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 mean binocular MLMT
score change (intervention minus control group difference of 1.6;
95% CI, 0.72, 2.41; p=0.001). After crossing over to receive
LUXTURNA, participants in the control group showed a similar
response to those in the intervention group. This score change has
been sustained for at least three years for the original
intervention group and at least two years in the crossover group of
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 averaged over both eyes
(p<0.001) and first assigned eye MLMT change score (p=0.001)
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.
Three ocular serious adverse events (SAEs) were
reported in the clinical program. One SAE related to the surgical
procedure in one eye of a Phase 3 participant, in which there was
foveal thinning that resulted in unresolved loss of foveal
function. One additional Phase 3 participant who continued into the
long-term follow-up study reported an SAE of retinal detachment 4
years after vector administration assessed as related to the
administration procedure. The third 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 5 percent or greater of the combined Phase 1 and Phase
3 trial participants included 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).
Indication and Important Safety Information for LUXTURNA
in the United States LUXTURNA 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. In clinical studies, the interval between
the subretinal injections into the two eyes ranged from 7 to 14
days and 1.7 to 4.6 years. 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.
About Inherited Retinal Disease (IRD) Caused by
Confirmed Biallelic RPE65 MutationsInherited 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.
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.
About Gene TherapyGene 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, commercial company committed to
discovering, developing and delivering gene therapies, we
challenge the inevitability of genetic
diseases, including blindness, hemophilia, lysosomal
storage disorders 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.
Spark Therapeutics 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). 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 the improvements in functional vision demonstrated by LUXTURNA
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
Relations Contact:Ryan AsayRyan.asay@sparktx.com(215)
239-6424 |
Media
Contact:Monique da
Silvacommunications@sparktx.com (215) 282-7470 |
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