Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a developer of innovative
RNA-based therapeutics, today provided an update on its discussions with
the U.S. Food and Drug Administration (FDA) regarding its planned New
Drug Application (NDA) submission for the approval of eteplirsen for the
treatment of Duchenne muscular dystrophy (DMD).
In meeting minutes received last week from a Type B Pre-NDA meeting that
took place in September 2014, the FDA provided updated guidance
regarding the specific data to be included as part of, or at the time
of, Sarepta’s NDA submission. The guidance states that additional data
are now required as part of the NDA submission, including the results
from an independent assessment of dystrophin images and the 168-week
clinical data from study 202. Additionally, the guidance requests more
specific data including a minimum duration of safety in new patients
exposed to eteplirsen, patient-level natural history data to be obtained
by Sarepta from independent academic institutions, and MRI data from a
recent study conducted by an independent academic group. The FDA
indicated that further discussion with Sarepta “will be necessary to
determine what would constitute a complete NDA.” Based on these
requests, Sarepta plans to submit an NDA by mid-year 2015, pending any
additional requests from further discussions with the FDA.
"We are committed to satisfying the FDA’s updated requests for these
specific data to be included as part of an NDA submission and will
continue to work with the Agency toward the goal of a complete and
acceptable NDA filing," said Chris Garabedian, president and chief
executive officer of Sarepta Therapeutics. "We believe all of the data
requests and additional FDA discussions that have currently been
outlined can be completed in time for an NDA submission by mid-year
2015. Obtaining an FDA approval of eteplirsen for the DMD patients who
may benefit from the drug continues to be our highest priority.”
Excerpts from the Pre-NDA Meeting Minutes related to information that
the FDA is requesting as part of an NDA submission included:
"The sponsor should include 3-month data from at least 12 to 24 newly
exposed patients at the time the NDA is submitted."
"Available data from the other patients enrolled in the new
eteplirsen studies (studies 301, 203, 204) should also be included at
the time the NDA is submitted, even if exposure is less than 3 months in
duration."
"Additional data from later time points and from newly enrolled
patients should be submitted in the 120-Day Safety Update."
"FDA strongly advises the sponsor to obtain and submit patient-level
natural history data. FDA is prepared to appeal to the academic
groups holding the data to allow the sponsor a means to acquire the
data."
"The study 201/202 clinical site inspection conducted in May, 2014,
after the issuance of the April 15, 2014, guidance letter, uncovered
marked disparities in the immunohistochemistry methodology and concerns
about the reproducibility of the data. The lack of confirmation
of robust dystrophin measurement during the site visit necessitates
including the independent assessment of dystrophin-positive fibers and
168-week efficacy data from study 201/202 in the NDA."
“FDA strongly urged the sponsor to submit the MRI data with
appropriate natural history controls.”
The FDA also stated that “[a]dditional discussion between the sponsor
and the FDA will be necessary to determine what would constitute a
complete NDA.”
Conference Call Information
Sarepta will hold a conference call to discuss this update today at 8:00
a.m. EDT (5:00 a.m. PDT). The conference call may be accessed by dialing
800.708.4539 for domestic callers and 847.619.6396 for international
callers. The passcode for the call is 38376370. Please specify to the
operator that you would like to join the "Sarepta Regulatory Update
Call." The conference call will be webcast live under the investor
relations section of Sarepta's website at www.sarepta.com
and will be archived there following the call for 90 days. Please
connect to Sarepta's website several minutes prior to the start of the
broadcast to ensure adequate time for any software download that may be
necessary. An audio replay will be available through November 3, 2014 by
calling 888.843.7419 or 630.652.3042 and entering access code 38376370.
About Duchenne Muscular Dystrophy
DMD is an X-linked rare degenerative neuromuscular disorder causing
severe progressive muscle loss and premature death. DMD affects
approximately one in every 3,500 boys born worldwide. A devastating and
incurable muscle-wasting disease, DMD is associated with specific errors
in the gene that codes for dystrophin, a protein that plays a key
structural role in muscle fiber function. Progressive muscle weakness in
the lower limbs spreads to the arms, neck and other areas. Eventually,
increasing difficulty in breathing due to respiratory muscle dysfunction
requires ventilation support, and cardiac dysfunction can lead to heart
failure. The condition is universally fatal, and death usually occurs
before the age of 30.
About Eteplirsen
Eteplirsen is Sarepta's lead drug candidate and is designed to address
the underlying cause of DMD by enabling the production of a functional
dystrophin protein. Data from clinical studies of eteplirsen in DMD
patients have demonstrated a broadly favorable safety and tolerability
profile and restoration of dystrophin protein expression.
Eteplirsen uses Sarepta's novel phosphorodiamidate morpholino oligomer
(PMO)-based chemistry and proprietary exon-skipping technology to skip
mutations affecting exon 51 of the dystrophin gene. Approximately 13
percent of the total DMD population is amenable to exon 51 skipping. By
skipping exon 51, eteplirsen may restore the gene's ability to make a
shorter, but still functional, form of dystrophin from messenger RNA, or
mRNA. Promoting the synthesis of a truncated dystrophin protein is
intended to stabilize or significantly slow the disease process and
prolong and improve the quality of life for patients with DMD. Sarepta
is also developing other PMO-based exon-skipping drug candidates
intended to treat additional patients with DMD.
About Sarepta Therapeutics
Sarepta Therapeutics is focused on developing first-in-class RNA-based
therapeutics to improve and save the lives of people affected by serious
and life-threatening rare and infectious diseases. The Company's diverse
pipeline includes its lead program eteplirsen, for DMD, as well as
potential treatments for some of the world's most lethal infectious
diseases. Sarepta aims to build a leading, independent biotech company
dedicated to translating its RNA-based science into transformational
therapeutics for patients who face significant unmet medical needs. For
more information, please visit us at www.sarepta.com.
Forward-Looking Statements and Information
This press release contains forward-looking statements. These
forward-looking statements generally can be identified by the use of
words such as “believes or belief,” “anticipates,” “plans,” “expects,”
“will,” “intends,” “potential,” “possible,” “advance” and similar
expressions. These forward-looking statements include statements about
Sarepta’s planned timing for an NDA submission for eteplirsen in the
treatment of DMD; Sarepta’s plans to work with the FDA towards the goal
of a complete and acceptable NDA filing; Sarepta’s ability to satisfy
the additional FDA requests; the timing and submission of additional
data, analysis and other information to the FDA necessary for the FDA to
make regulatory determinations; the timing of and ability to initiate
additional studies for eteplirsen and other follow-on exons; and the
potential regulatory approval of eteplirsen.
Each forward-looking statement contained in this press release is
subject to risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by such statement.
Applicable risks and uncertainties include, among others: we
may not be able to comply with all FDA requests; the FDA may
determine that substantial additional data is required for accelerated
or other approval of eteplirsen or that our NDA submission for
eteplirsen does not qualify for filing, even with additional
information; the results of our ongoing and new clinical trials may not
be positive; there may be delays in timelines relating to an NDA
submission, initiating clinical trials, or making a product commercially
available for regulatory or internal reasons; we may not be able to
manufacture sufficient supply for clinical trials or commercialization;
agency or court decisions with respect to our patents or those of third
parties may negatively impact our business and those identified under
the heading “Risk Factors” in Sarepta’s Quarterly Report on Form 10-Q
for the quarter ended June 30, 2014 filed with the Securities and
Exchange Commission (SEC), and Sarepta’s other filings with the SEC.
Any of the foregoing risks could materially and adversely affect
Sarepta’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 the Company’s
filings with the SEC. 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.
Copyright Business Wire 2014