FDA Advisory Committee Discusses Clinical Data Package for BioMarin’s Kyndrisa(TM) (drisapersen) for the Treatment of Duch...
November 24 2015 - 6:56PM
-- If Approved, Kyndrisa Would Become the First
Disease-Modifying Therapy for Patients With Duchenne Muscular
Dystrophy in the United States Amenable to Exon 51 Skipping --
BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) announced today that the
Peripheral and Central Nervous System Drugs Advisory Committee of
the U.S. Food and Drug Administration (FDA) met to discuss the data
submitted to support the New Drug Application (NDA) for KyndrisaTM
(drisapersen) for the treatment of Duchenne muscular dystrophy
(Duchenne) amenable to exon 51 skipping. The committee
reviewed the Kyndrisa data package, which includes three
randomized, placebo controlled trials with more than 300 patients
and more than 500 patient years of exposure. The committee
discussed the overall strengths and weaknesses of the application
but was not asked to vote on a recommendation for approval of
Kyndrisa.
"I’d like to thank the patients, families and physicians who
participated in Kyndrisa clinical trials and in today’s panel
discussion,” said Jean-Jacques Bienaimé, chairman and chief
executive officer of BioMarin. “We look forward to continuing
our efforts to bring Kyndrisa to the Duchenne community.
After today’s meeting, our next step is to continue working
with the FDA as they complete their regulatory review.”
“The Committee’s discussion today is part of the FDA’s
evaluation of Kyndrisa and the potential for a treatment option for
the Duchenne community in the United States,” said Debra Miller,
co-founder and CEO of CureDuchenne. “We have long supported the
research and development of Kyndrisa and eagerly anticipate the
FDA’s decision, which could make our hopes for therapy a
reality.”
In addition to discussing the overall strengths and weaknesses
of the data supporting the efficacy of drisapersen and the
acceptability of its safety profile, the FDA’s advisory committee
was asked to discuss the following issues and vote on the
associated questions.
Discussion Issues |
Voting Questions (Results) |
1. Discuss the strength of efficacy evidence provided by Study 1
with particular consideration of the following issues and any other
issues that you think may be important:a. Discrepant results of the
two dosing regimens despite similar exposure to drisapersenb. Lack
of statistically significant results on secondary endpoints
|
What overall impact do the issues discussed in question #1 have on
the persuasiveness of Study 1?a. Strengthen (1)b. Weaken (9)c. No
effect (7) |
2. Discuss the strength of efficacy evidence provided by Study 2
with particular consideration of the following issues and any other
issues that you think may be important:a. Lack of statistical
significance of the primary outcome measure (p = 0.07 on ITT
analysis, p = 0.23 on per protocol analysis)b. 3 mg/kg group
numerically inferior to placeboc. 6 mg/kg group numerically
inferior to placebo for most secondary endpoints |
What overall impact do the issues discussed in question #2 have on
the persuasiveness of Study 2?a. Strengthen (0)b. Weaken (5)c. No
effect (12) |
3. Discuss the evidence provided by Study 3 with particular
consideration of the following issues and any other issues that you
think may be important:a. Lack of statistical significance of the
primary outcome measure (p = 0.42) in a well-powered Phase 3
studyb. Lack of nominally statistically significant results on all
secondary endpoints |
What is the impact of Study 3 results on the persuasiveness of
findings in Study 1 and Study 2?a. Strengthen (0)b. Weaken (15)c.
No effect (2) |
4. Drisapersen was designed to increase production of dystrophin.
Discuss the evidence presented about dystrophin production,
including the following:a. Similar number of patients with skipped
band of mRNA detected by PCR in the placebo group and drisapersen
groupb. Similar number of patients with dystrophin increase from
baseline in the placebo group and drisapersen group on
immunofluorescence testingc. Lack of notable increase in dystrophin
with drisapersen treatment on western blot analysis (pre-treatment
levels <1% and post-treatment levels <1%) |
What is the impact of the dystrophin results on the interpretation
of the clinical results?a. Strengthen (0)b. Weaken (6)c. No effect
(10)not voting (1) |
The Committee's feedback will be considered by the FDA in its
review of the NDA for Kyndrisa. The FDA is not bound by the
Committee's guidance, but takes its advice into consideration when
reviewing investigational medicines.
The FDA has set a target action date of December 27, 2015, under
the Prescription Drug User Fee Act (PDUFA). An application for
marketing approval of Kyndrisa is also pending in the European
Union.
About Duchenne Muscular Dystrophy
Changes in the dystrophin gene (mutations) that lead to the near
absence of dystrophin protein result in the most severe form of
dystrophin deficient muscular dystrophy, Duchenne muscular
dystrophy, also known as just Duchenne. Dystrophin protein plays an
important structural role in the performance of muscles. Without
dystrophin, boys living with Duchenne experience progressive muscle
weakness, causing serious medical complications including serious
heart or respiratory-related complications, resulting in death in
early adulthood.
Primarily affecting boys, Duchenne affects approximately 1 in
every 3,500-5,000 male children, making it the most common fatal
genetic disorder diagnosed in childhood.
There is currently no FDA approved therapy designed specifically
to treat Duchenne.
About Kyndrisa and Exon Skipping
Kyndrisa is an antisense oligonucleotide that induces exon
skipping to provide a molecular patch for dystrophin transcripts
produced by certain mutated dystrophin genes. Exons are the parts
of a gene that contain the instructions for generating a protein.
In applicable cases, skipping an exon near the mutation allows for
the production of a truncated but functional dystrophin
protein.
Kyndrisa is the first and only investigational medicine designed
specifically for the treatment of Duchenne that has received orphan
drug, breakthrough drug, fast track and priority review status by
the FDA. The Kyndrisa clinical development program is the
largest ever submitted to the FDA for the condition and includes
more than 300 Duchenne patients and multiple randomized
placebo-controlled studies.
About BioMarin
BioMarin is a global biotechnology company that develops and
commercializes innovative therapies for patients with serious and
life-threatening rare and ultra-rare genetic diseases. The
company's portfolio consists of five commercialized products and
multiple clinical and pre-clinical product candidates. For
additional information, please visit www.BMRN.com.
Forward-Looking Statement
This press release contains forward-looking statements about the
business prospects of BioMarin Pharmaceutical Inc., including,
without limitation, statements about: expectations regarding the
FDA’s review of the Kyndrisa NDA, outcomes of the review of such
filings; and the possible approval of Kyndrisa. These
forward-looking statements are predictions and involve risks and
uncertainties such that actual results may differ materially from
these statements. These risks and uncertainties include, among
others: results and timing of current and planned clinical trials
of Kyndrisa; the content and timing of decisions by the FDA, and
other regulatory authorities concerning Kyndrisa; and those factors
detailed in BioMarin's filings with the Securities and Exchange
Commission, including, without limitation, the factors contained
under the caption "Risk Factors" in BioMarin's 2014 Annual Report
on Form 10-K, as amended, and the factors contained in BioMarin's
reports on Form 8-K. Stockholders are urged not to place undue
reliance on forward-looking statements, which speak only as of the
date hereof. BioMarin is under no obligation, and expressly
disclaims any obligation to update or alter any forward-looking
statement, whether as a result of new information, future events or
otherwise.
Kyndrisa™ is our trademark, and BioMarin® is a registered
trademark of BioMarin Pharmaceutical Inc.
Investors:
Traci McCarty
BioMarin Pharmaceutical Inc.
(415) 455-7558
Media:
Debra Charlesworth
BioMarin Pharmaceutical Inc.
(415) 455-7451
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