Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision
genetic medicine for rare diseases, today announced that the U.S.
Food and Drug Administration (FDA) has approved VYONDYS 53™
(golodirsen). VYONDYS 53 is an antisense oligonucleotide from
Sarepta’s phosphorodiamidate morpholino oligomer (PMO) platform,
indicated for the treatment of Duchenne muscular dystrophy (DMD) in
patients with a confirmed mutation amenable to exon 53 skipping.
This indication is based on a statistically significant increase in
dystrophin production in skeletal muscle observed in patients
treated with VYONDYS 53, which is reasonably likely to predict
clinical benefit for those patients who are exon 53 amenable.
Consistent with the accelerated approval pathway, the continued
approval of VYONDYS 53 may be contingent on confirmation of a
clinical benefit in this post-marketing confirmatory trial.
Sarepta’s placebo-controlled, post-marketing
confirmatory trial to support the VYONDYS 53 accelerated approval –
titled ESSENCE – is currently enrolling and expected to conclude by
2024.
Hypersensitivity reactions, including rash,
pyrexia (fever), pruritis, urticaria (hives), dermatitis, and skin
exfoliation have occurred in patients who were treated with VYONDYS
53. Renal toxicity was observed in animal studies. Although not
observed in the clinical studies with VYONDYS 53, renal toxicity,
including potentially fatal glomerulonephritis, has been observed
after administration of some antisense oligonucleotides. The most
common adverse reactions that occurred in at least 20% of VYONDYS
53-treated patients and more frequently than in placebo-treated
patients were headache (41%), pyrexia (41%), fall (29%), abdominal
pain (27%), nasopharyngitis (27%), cough (27%), vomiting (27%), and
nausea (20%).
Following a New Drug Application (NDA)
submission to and review by the Division of Neurology Products (the
Review Division) for VYONDYS 53, which the Review Division
recommended for approval, the Office of Drug Evaluation 1 issued a
complete response letter (CRL) in August of 2019. Thereafter,
Sarepta made a formal dispute resolution request as outlined in
relevant FDA Guidance. With the support of the Review Division, the
matters raised in the CRL were rapidly evaluated and resolved by
Dr. Peter Stein, Director of the Office of New Drugs (OND). OND
granted the Company’s appeal and Sarepta re-submitted its NDA to
the Review Division, which worked expeditiously to review and
approve VYONDYS 53.
“Today is monumental for Sarepta and, more
importantly, for the DMD community,” said Doug Ingram, president
and chief executive officer, Sarepta. “VYONDYS 53, our second
approved exon-skipping RNA therapy for DMD, may treat up to 8% of
the DMD community, representing those patients who have a confirmed
exon 53 amenable mutation. Along with EXONDYS 51®
(eteplirsen), we now offer treatment options for approximately 20%
of those with DMD in the U.S.”
Ingram continued, “In the span of four months,
we commenced and completed the formal dispute resolution process
culminating in the grant of our appeal, resubmitted our NDA and
obtained an approval – a great benefit to DMD patients awaiting
treatment. This unprecedented timing could not have been achieved
without the commitment of the Review Division under the leadership
of Dr. Billy Dunn, and the Office of New Drugs, which expeditiously
heard and granted our appeal. Along with the DMD community,
we owe our gratitude to both the Review Division and the OND for
their objective, evidence-based approach to this review, for their
fairness, and for the sense of urgency with which they addressed
and resolved the CRL and granted this approval.”
“With the approval of VYONDYS 53, up to another
8% of Duchenne families will have a therapy to treat this
devastating disease,” said Pat Furlong, founding president and
chief executive officer, Parent Project Muscular Dystrophy (PPMD).
“For 25 years, PPMD has been working with researchers, clinicians,
industry, and the Duchenne community to find treatments for all
people living with Duchenne. And while we need to ensure that these
approved therapies are accessible for patients, today we celebrate
this approval and thank Sarepta for their continued leadership in
the fight to end Duchenne.”
VYONDYS 53 is priced at parity to EXONDYS 51,
the price of which has not increased since its launch in 2016.
Patients and physicians can access more information at
www.SareptAssist.com or by calling 1-888-727-3782.
About VYONDYS 53 VYONDYS 53 is
an antisense oligonucleotide indicated for the treatment of
Duchenne muscular dystrophy in patients who have a confirmed
mutation of the DMD gene that is amenable to exon 53 skipping.
VYONDYS 53 uses Sarepta’s proprietary phosphorodiamidate morpholino
oligomer (PMO) chemistry and exon-skipping technology to bind to
exon 53 of dystrophin pre-mRNA, resulting in exclusion, or
“skipping,” of this exon during mRNA processing in patients with
genetic mutations that are amenable to exon 53 skipping. Exon
skipping is intended to allow for production of an internally
truncated dystrophin protein.
VYONDYS 53 is approved under accelerated review
based on an increase in dystrophin production in skeletal muscle of
patients amenable to exon 53 skipping. Continued approval may be
contingent upon verification of a clinical benefit in confirmatory
trials.
VYONDYS 53 has met the full statutory standards
for safety and effectiveness and as such is not considered
investigational or experimental.
Important Safety Information for VYONDYS
53Hypersensitivity reactions, including rash, pyrexia,
pruritus, urticaria, dermatitis, and skin exfoliation have occurred
in VYONDYS 53-treated patients, some requiring treatment. If
a hypersensitivity reaction occurs, institute appropriate medical
treatment and consider slowing the infusion or interrupting the
VYONDYS 53 therapy.
Renal toxicity was observed in animals who
received golodirsen. Although renal toxicity was not observed in
the clinical studies with VYONDYS 53, renal toxicity, including
potentially fatal glomerulonephritis, has been observed after
administration of some antisense oligonucleotides. Renal function
should be monitored in patients taking VYONDYS 53. Because of the
effect of reduced skeletal muscle mass on creatinine measurements,
creatinine may not be a reliable measure of renal function in DMD
patients. Measurement of glomerular filtration rate (GFR) by
24-hour urine collection prior to initiation of therapy is
recommended. Monthly monitoring for proteinuria by dipstick
urinalysis and monitoring of serum cystatin C every three months is
recommended. In the case of a confirmed dipstick proteinuria of 2+
or greater or elevated serum cystatin C, a 24-hour urine collection
to quantify proteinuria and assess GFR should be performed.
Adverse reactions observed in at least 20% of
treated patients and greater than placebo were (VYONDYS 53,
placebo): headache (41%, 10%), pyrexia (41%, 14%), fall (29%,
19%), abdominal pain (27%, 10%), nasopharyngitis (27%, 14%), cough
(27%, 19%), vomiting (27%, 19%), and nausea (20%, 10%).
Other adverse reactions that occurred at a
frequency greater than 5% of VYONDYS 53-treated patients and
at a greater frequency than placebo were administration site pain,
back pain, pain, diarrhea, dizziness, ligament sprain, contusion,
influenza, oropharyngeal pain, rhinitis, skin abrasion, ear
infection, seasonal allergy, tachycardia, catheter site related
reaction, constipation, and fracture.
For further information, please see the full
Prescribing Information.
About EXONDYS 51
EXONDYS 51 uses Sarepta’s proprietary
phosphorodiamidate morpholino oligomer (PMO) chemistry and
exon-skipping technology to skip exon 51 of the dystrophin gene.
EXONDYS 51 is designed to bind to exon 51 of dystrophin pre-mRNA,
resulting in exclusion of this exon during mRNA processing in
patients with genetic mutations that are amenable to exon 51
skipping. Exon skipping is intended to allow for production of an
internally truncated dystrophin protein.
Important Safety Information About
EXONDYS 51
Hypersensitivity reactions, including rash and
urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, and
hypotension, have occurred in patients who were treated with
EXONDYS 51. If a hypersensitivity reaction occurs, institute
appropriate medical treatment and consider slowing the infusion or
interrupting the EXONDYS 51 therapy.
Adverse reactions in DMD patients (N=8) treated
with EXONDYS 51 30 mg or 50 mg/kg/week by intravenous (IV) infusion
with an incidence of at least 25% more than placebo (N=4) (Study 1,
24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%),
vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most
common adverse reactions were balance disorder and vomiting.
Because of the small numbers of patients, these represent crude
frequencies that may not reflect the frequencies observed in
practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is
not recommended.
In the 88 patients who received ≥30 mg/kg/week
of EXONDYS 51 for up to 208 weeks in clinical studies, the
following events were reported in ≥10% of patients and occurred
more frequently than on the same dose in Study 1: vomiting,
contusion, excoriation, arthralgia, rash, catheter site pain, and
upper respiratory tract infection.
For further information, please see the full
Prescribing Information.
About Sarepta
TherapeuticsSarepta is at the forefront of precision
genetic medicine, having built an impressive and competitive
position in Duchenne muscular dystrophy (DMD) and more recently in
gene therapies for 6 Limb-girdle muscular dystrophy diseases
(LGMD), Charcot-Marie-Tooth (CMT), MPS IIIA, Pompe and other
CNS-related disorders, totaling over 20 therapies in various stages
of development. The Company’s programs and research focus span
several therapeutic modalities, including RNA, gene therapy and
gene editing. Sarepta is fueled by an audacious but important
mission: to profoundly improve and extend the lives of patients
with rare genetic-based diseases. For more information, please
visit www.sarepta.com.
Forward-Looking StatementThis
press release contains "forward-looking statements." Any statements
contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements.
Words such as "believes," "anticipates," "plans," "expects,"
"will," "intends," "potential," "possible" and similar expressions
are intended to identify forward-looking statements. These
forward-looking statements include statements regarding the
immediate commencement of commercial distribution of VYONDYS 53 in
the U.S.; VYONDYS 53’s continued approval for its indication
potentially being contingent upon verification of a clinical
benefit in confirmatory trials; the potential benefits and risks of
VYONDYS 53; VYONDYS 53’s potential to treat up to another 8% of
those living with DMD; the potential of EXONDYS 51 and VYONDYS 53
to treat up to 20% of those with DMD in the U.S.; exon skipping’s
intention to allow for production of an internally truncated
dystrophin protein; and our mission to profoundly improve and
extend the lives of patients with rare genetic-based diseases.
These forward-looking statements involve risks
and uncertainties, many of which are beyond Sarepta’s control.
Known risk factors include, among others: the planned commercial
launch in the U.S. for VYONDYS 53 may not be successful for various
reasons including the actual market size and drug supply needed may
not be consistent with the company’s expectations and its executed
commercial readiness plans, the degree to which VYONDYS 53 is
accepted by patients and prescribed by physicians, manufacturing
limitations that may not be anticipated or resolved for in a timely
manner or at all, the efficiency of our manufacturing, sales,
distribution and specialty pharmacy network in getting VYONDYS 53
to the market and future economic, competitive, reimbursement and
regulatory conditions that could negatively impact the commercial
launch of VYONDYS 53; we may not be able to comply with all FDA
post-approval commitments and requirements with respect to EXONDYS
51 and VYONDYS 53 in a timely manner or at all; we may not be able
to complete clinical trials required by the FDA or other regulatory
authorities for approval of our product candidates; the results of
our ongoing research and development efforts and clinical trials
for our products and product candidates may not be positive or
consistent with prior results or demonstrate a safe treatment
benefit or support an NDA or a BLA filing, positive advisory
committee recommendation or marketing approval by the FDA or other
regulatory authority; we may not be able to execute on our business
plans including meeting our expected or planned regulatory
milestones and timelines, clinical development plans and bringing
our product candidates to market, including the commercialization
of VYONDYS 53, for various reasons, including factors outside of
our control, such as possible limitations of company financial and
other resources, manufacturing limitations that may not be
anticipated or resolved for in a timely manner or at all, and
regulatory, court or agency decisions, such as decisions by the
United States Patent and Trademark Office with respect to patents
that cover our product and product candidates; and those risks
identified under the heading “Risk Factors” in Sarepta’s most
recent Annual Report on Form 10-K for the year ended December 31,
2018, and most recent Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission (SEC) as well as other SEC
filings made by the Company which you are encouraged to review.
Any of the foregoing risks could materially and
adversely affect the Company’s business, results of operations and
the trading price of Sarepta’s common stock. For a detailed
description of risks and uncertainties Sarepta faces, you are
encouraged to review Sarepta's 2018 Annual Report on Form 10-K and
most recent Quarterly Report on Form 10-Q filed with the SEC as
well as other SEC filings made by Sarepta. We caution investors not
to place considerable reliance on the forward-looking statements
contained in this press release. Sarepta does not undertake any
obligation to publicly update its forward-looking statements based
on events or circumstances after the date hereof.
Internet Posting of
Information
We routinely post information that may be
important to investors in the 'For Investors' section of our
website at www.sarepta.com. We encourage investors and
potential investors to consult our website regularly for important
information about us.
Source: Sarepta Therapeutics, Inc.
Sarepta Therapeutics, Inc.
Investors: Ian Estepan,
617-274-4052iestepan@sarepta.com Media:Tracy Sorrentino,
617-301-8566tsorrentino@sarepta.com
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