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FDA Advisory Committee Discusses Clinical Data Package for BioMarin’s Kyndrisa(TM) (drisapersen) for the Treatment of Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

-- 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 --

SAN RAFAEL, Calif., Nov. 24, 2015 (GLOBE NEWSWIRE) -- 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 drisapersen
b. 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 placebo
c. 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 study
b. 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 group
b. Similar number of patients with dystrophin increase from baseline in the placebo group and drisapersen group on immunofluorescence testing
c. 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

Source:BioMarin Pharmaceutical Inc.