LUXTURNA would be
first gene therapy for a genetic disease approved in both U.S. and
EU
LUXTURNA would be
first and only gene therapy approved in EU to treat patients with
vision loss due to inherited retinal dystrophy caused by confirmed
biallelic RPE65 mutations and who
have sufficient viable retinal cells, a condition leading to total
blindness in most patients
Positive opinion
based on robust data package supporting safety, efficacy and
durability of response for up to three years after one-time
treatment with LUXTURNA
PHILADELPHIA, Sept. 21, 2018 (GLOBE NEWSWIRE) --
Spark Therapeutics (NASDAQ: ONCE), a fully integrated, commercial
gene therapy company dedicated to challenging the inevitability of
genetic disease today announced that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) adopted a positive opinion recommending approval of 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.
"We are encouraged by today's
decision, which further affirms our pioneering clinical program and
brings LUXTURNA one step closer to patients with inherited retinal
disease (IRD) caused by mutations in both copies of
the RPE65 gene in the European
Union," said Katherine A. High, M.D., president and head of
research & development at Spark Therapeutics. "Along with
Novartis, we look forward to continuing our productive, ongoing
dialogue with EMA toward potential marketing authorization to make
LUXTURNA the first and only treatment for appropriate patients with
this inherited retinal disease (IRD) in the European Union."
The positive CHMP opinion is 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 on both
copies of the RPE65 gene. The
Phase 3 trial was the first randomized, controlled Phase 3 gene
therapy trial for a genetic disease. Spark Therapeutics has
received orphan product designation for LUXTURNA from EMA for the
treatment of inherited retinal dystrophies.
"Inherited retinal diseases are a heterogenous
group of degenerative conditions that represent the major cause of
blindness in childhood and active working life. This opinion
represents a hopeful milestone for current and future patients who
may ultimately benefit from gene therapy," 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.
A marketing authorization decision
from the European Commission is anticipated approximately within
two months. If approved, the authorization will be valid in all
28-member states of the European Union, as well as Iceland,
Liechtenstein and Norway. In January 2018, Spark Therapeutics
entered into a licensing and supply agreement with Novartis to
commercialize LUXTURNA when and if approved in Europe and all
markets outside the U.S.
LUXTURNA (voretigene
neparvovec-rzyl) 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 safety 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 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, 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. Secondary endpoints included white light
full-field light sensitivity threshold (FST) testing averaged over
both eyes, first assigned eye MLMT 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 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 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 (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 and a sustained
reduction in VA. One additional Phase 3 participant 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 U.S.
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
greater than or equal to 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 Mutations
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.
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 the
Novartis and Spark Therapeutics Licensing and Supply
Agreement
In January 2018, Spark Therapeutics entered into a licensing and
supply agreement with Novartis covering development, registration
and commercialization rights to LUXTURNA in markets outside the
U.S. Commercialization rights will be transferred to Novartis upon
successful completion of registration and issuance of marketing
authorization. Novartis has exclusive rights to pursue development,
registration and commercialization in all other countries outside
the U.S., and Spark Therapeutics would supply the gene therapy to
Novartis.
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(TM) (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
when expected, or at all; and (ii) 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: |
|
|
Media Contact: |
Ryan
Asay |
|
|
Monique da Silva |
Ryan.asay@sparktx.com |
|
|
communications@sparktx.com |
(215)
239-6424 |
|
|
(215)
282-7470 |
This
announcement is distributed by Nasdaq Corporate Solutions on behalf
of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: Spark Therapeutics, Inc. via Globenewswire
Onconetix (NASDAQ:ONCE)
Historical Stock Chart
From Mar 2024 to Apr 2024
Onconetix (NASDAQ:ONCE)
Historical Stock Chart
From Apr 2023 to Apr 2024