BioMarin Announces Two Oral and 19 Poster Presentations at the Society for the Study of Inborn Errors of Metabolism 2015 Annual Meeting

Oral Presentations Include Long-Term Safety and Efficacy with Pegvaliase for Control of Blood Phenylalanine in Adults with PKU and a Review of the Ongoing Development Program for Reveglucosidase Alfa for Late Onset Pompe Disease

Poster Presentations Include 120-Week Safety and Efficacy Data with VIMIZIM® (elosulfase alfa)

SAN RAFAEL, Calif., Aug. 31, 2015 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) announced today that the company will present data in two oral and 19 poster presentations at the Society for the Study of Inborn Errors of Metabolism 2015 Annual Meeting which will be held on September 1-4 in Lyon, France.

In an oral platform session, long-term efficacy and safety data from a Phase 2 extension study of pegvaliase (PEG-PAL, rAvPAL-PEG, BMN 165) in adults with phenylketonuria (PKU) will be presented. PKU is a rare genetic condition in which the body cannot metabolize the essential amino acid phenylalanine. Designated Orphan Drug status in the United States and European Union, pegvaliase is an enzyme substitution therapy that is designed to substitute phenylalanine ammonia lyase for phenylalanine hydroxylase, the enzyme deficient in people with PKU.

A separate oral platform presentation will provide an overview of the reveglucosidase alfa (BMN 701) clinical program in late onset Pompe disease. In addition, the overview will summarize the three ongoing trials; the ongoing Phase 3 INSPIRE trial, a switchover study designed to assess safety and efficacy of reveglucosidase alfa in patients previously treated with enzyme replacement therapy; an observational study in patients with late onset Pompe disease; and a transdiaphragmatic stimulation study in late onset Pompe patients treated with reveglucosidase alfa. The overview also includes a review of nonclinical activity as well as interim safety and efficacy results in treatment naïve, late-onset Pompe patients treated with reveglucosidase alfa.

Pompe disease is an inherited condition caused by the deficiency in the enzyme acid alpha-glucosidase, which leads to progressive weakening of muscles in the body, including diaphragm muscles essential for breathing. Reveglucosidase alfa is a novel fusion protein of insulin-like growth factor 2 and acid alpha-glucosidase, designed to target delivery to cell structures called lysosomes where the enzyme is most needed.

"We are committed to patients with rare inherited metabolic disorders. We continue to evaluate multiple therapies across disease states over the long term to both understand the impact of our medicines on patients, as well as to better understand the biology of the disease," said Hank Fuchs, M.D., Executive Vice President and Chief Medical Officer at BioMarin. "With promising results from our late stage and long term clinical studies, we are one step closer to potentially bringing new treatments to patients in need. Our more than twenty presentations across multiple conditions underscores our growing research to advance the standard of care for children and adults with rare conditions."

Additionally, data will be presented from 11 abstracts on mucopolysaccharidosis (MPS), a group of metabolic disorders caused by the deficiency of specific enzymes, including five abstracts evaluating VIMIZIM® (elosulfase alfa) in people with Morquio A Syndrome (MPS IVA), a specific form of the disease. The other studies for MPS also provide understanding into the challenges associated with the disease, such as the management of fertility and pregnancy.

Listing of Posters and Presentations at Society for the Study of Inborn Errors of Metabolism 2015 Annual Meeting

Oral Presentations

Title Authors
An international, phase 3, switchover study of reveglucosidase alfa (BMN 701) in subjects with late onset Pompe disease (INSPIRE study)* Geberhiwot T, Byrne B, Eyskens F, Hughes D, Kissel J, Mengel E, Mozaffar T, Pestronk A, Roberts M, Schoser B, Sivakumar K, Statland J, Young P, Heusner C, Walsh L
Presentation: Wed., Sept. 2, 2015  
*Overview of INSPIRE study (trial-in-progress) only and does not include data  
Evaluation of long-term safety and efficacy with rAvPAL-PEG (BMN 165) for control of blood phenylalanine levels in adults with phenylketonuria (PKU)* Longo N, Thomas J, Wasserstein M, Burton B, Vockley G, Grange D, Hillman R, Harding C, Dimmock D, Shur N, Adams D, Rizzo W, Whitley C, Goodin K, Decker C, Merilainen M, Li M, Bolt K, Schweighardt B, Shpilberg S, Muthalif M, Zori R
Presentation: Thurs., Sept. 3, 2015  

Poster Presentations

Mucopolysaccharidosis (MPS)  
Title Authors
Urine keratan sulfate (uKS) in Morquio A patients measured via LC-MS/MS method: improved KS detection as compared to dye-based methods and report of age-specific uKS reference ranges Pasquali M, Auray-Blais C, Ellsworth K, Fietz M, Giugliani R, Harmatz P, Izzo E, Lavoie P, la Marca G, Millington D, Trinh M-U, van Vlies N, Varfaj F, Wijburg F, Wood T, Zhang H, Miller N
Urine keratan sulfate (uKS) elevation in lysosomal storage disorders (LSDs): comparison of uKS levels in Morquio/mucopolysaccharidosis (MPS) IV versus non-Morquio LSDs Wijburg F, Auray-Blais C, Ellsworth K, Giugliani R, Harmatz P, Izzo E, Lavoie P, Millington D, Wood T, van Vlies N, Zhang H, Miller N.
Impact of mucopolysaccharidosis (MPS) on daily living, employment, general health and parenthood of adult patients Lavery C, Wedehase B, Harmatz P, Hendriksz CJ
Impact of elosulfase alfa on exercise capacity in patients with Morquio A syndrome in a randomised, double-blind, pilot study Burton B, Berger KI, Lewis GD, Tarnopolsky M, Mitchell JJ, Muschol N, Jones SA, Sutton VR, Pastores GM, Lau H, Sparkes R, Genter F, Shaywitz AJ, Harmatz P
Long-term outcomes of treatment with elosulfase alfa for Morquio A Syndrome (mucopolysaccharidosis IVA) Hendriksz C, Jones S, Decker C, Geberhiwot T, Van Tuyl A, Schweighardt B, Slasor P
Safety and pharmacodynamic activity of elosulfase alfa in pediatric patients less than 5 years of age with Morquio A Syndrome (Mucopolysaccharidosis IVA) Harmatz P, Jones SA, Bialer M, Parini R, Martin K, Wang H, Shaywitz A
Impact of long-term elosulfase alfa treatment on six-minute walk test distance in patients with Morquio A syndrome Harmatz P, Burton BK, Giugliani R, Hughes D, Mitchell JJ, Raiman J, Stewart F, Solano Villarreal ML, Slasor P, Shaywitz AJ
Impact of long-term elosulfase alfa treatment on three-minute stair climb test, pulmonary function tests and normalized urine keratan sulfate in patients with Morquio A syndrome Giugliani R, Burton BK, Harmatz P, Hughes D, Mitchell JJ, Raiman J, Solano Villarreal ML, Stewart F1, Slasor P, Shaywitz AJ
Management of fertility and pregnancy in individuals with mucopolysaccharidosis (MPS) Stewart F, Harmatz P, Braunlin E, Bentley A, Burton B, Guffon N, Hale S, Johnston T, Kircher S, Kochhar P, Mitchell J, Plöckinger U, Semotok J, Sisic Z
Medical issues and other challenges in adult patients with mucopolysaccharidosis (MPS) Mitchell J, Berger K, Quartel A, Braunlin E, Wang R, Pastores GM, White K, Jurecki E
Dose- and time-dependent clearance of lysosomal storage in the MPS IIIB mouse model by intracerebroventricular enzyme replacement therapy with BMN 250, a NAGLU-IGFII fusion protein Aoyagi-Scharber M, Vincelette J, Lawrence R, Crippen-Harmon D, Yip BK, Baridon B, Prill H, Minto W, Van Vleet J, Vitelli C, Adintori EG, Strong KM, Christianson T, Tiger PMN, Lo MJ, Holtzinger J, Chen E, Fitzpatrick PA, LeBowitz
Pompe disease  
Title Authors
Pulmonary function predictors (VC, FVC, MIP, MEP) of ventilator use in late-onset Pompe disease Quartel A, Mozaffar T, Roberts M, Young P, Johnson EM, Berger KI
Phenylketonuria (PKU)  
Title Authors
Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study Bilder DA, Kobori JA, Cohen-Pfeffer JL, Johnson EM, Jurecki ER, Grant ML
Evaluation of multiple dosing regimens in phase 2 studies of rAvPAL-PEG for control of blood phenylalanine levels in adults with phenylketonuria Thomas J, Longo N, Zori R, Burton B, Wasserstein M, Grange D, Vockley J, Hillman R, Harding C, Shur N, Adams D, Rice G, Rizzo W, Whitley C, Goodin K, McBride K, Decker C, Merilainen M, Li M, Schweighardt B, Dimmock D.
Evaluation of an induction, titration, and maintenance dosing regimen in a phase 2 study of rAvPAL-PEG for control of blood phenylalanine levels in adults with phenylketonuria (PKU) Zori R, Thomas J, Shur N, Rizzo W, Decker C, Merilainen M, Li M, Schweighthardt B, Longo N.
Phase 2 studies contribute to rAvPAL-PEG phase 3 trial design Harding C, Longo N, Thomas J, Burton B, Zori R, Bilder D, Posner J, Lieberman P, Merilainen M, Gu K, Schweighardt B, Weng H, Levy H
A randomized, placebo-controlled, double-blind study of sapropterin to treat symptoms of ADHD and executive dysfunction in children and adolescents with phenylketonuria Grant M, Cohen-Pfeffer J, McCandless S, Stahl SM, Bilder D, Jurecki ER, Yu S, Sanchez-Valle A, Dimmock D
CLN2 Disease  
Title Authors
Neuronal Ceroid Lipofuscinosis-2 (CLN2) disorder, a type of Batten disease caused by TPP1 enzyme deficiency: Current knowledge of the natural history from international experts Schulz A, Cohen-Pfeffer JL, Crystal R, de los Reyes E, Eto Y, Guelbert N, Héron B, Mikhailova S, Miller N, Mink J, Perez-Poyato M, Simonati A, Sims K, Williams RE
Real-world experience in the diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2): Report from an international collaboration of experts Miller N, Mole S, Cohen-Pfeffer JL, Crystal R, de los Reyes E, Eto Y, Fietz M, Heron B, Izzo E, Kohlschutter A, Lourenço CM, Noher de Halac I, Pearce DA, Simonati A, del Socorro Pérez Poyato M, Schulz A

Important Safety Information About Vimizim

Life-threatening allergic reactions, known as anaphylaxis, can occur during Vimizim® (elosulfase alfa) infusions. Due to the potential for anaphylaxis, appropriate medical support should be readily available when Vimizim is administered and for an appropriate period of time following administration.

Hypersensitivity reactions have been observed as early as 30 minutes from the start of infusion but as late as six days after infusion. Frequent symptoms of hypersensitivity reactions included anaphylactic reactions, urticaria, peripheral edema, cough, dyspnea, and flushing.

Because of the potential for hypersensitivity reactions, administer antihistamines with or without antipyretics prior to infusion. If severe hypersensitivity reactions occur, immediately stop the infusion of VIMIZIM and initiate appropriate treatment. Patients with acute febrile or respiratory illness at the time of VIMIZIM infusion may be at higher risk of life-threatening complications from hypersensitivity reactions.

Sleep apnea is common in MPS IVA patients. Evaluation of airway patency should be considered prior to initiation of treatment with VIMIZIM. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an acute reaction, or extreme drowsiness/sleep induced by antihistamine use.

Spinal or cervical cord compression (SCC) is a known and serious complication of MPS IVA and may occur as part of the natural history of the disease. In clinical trials, SCC was observed both in patients receiving VIMIZIM and patients receiving placebo. Patients with MPS IVA should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, urinary and fecal incontinence) and given appropriate clinical care.

All patients treated with VIMIZIM 2 mg/kg once per week in the placebo-controlled trial developed anti-drug antibodies.

VIMIZIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if VIMIZIM is present in human milk.

Safety and effectiveness in pediatric patients below 5 years of age have not been established.

In clinical trials, the most common adverse reactions (≥10%) occurring during infusion included pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue. The acute reactions requiring intervention were managed by either temporarily interrupting or discontinuing infusion, and administering additional antihistamine, antipyretics, or corticosteroids.

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About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio comprises five approved products and multiple clinical and pre-clinical product candidates. Approved products include Vimizim® (elosulfase alfa) for MPS IVA, a product wholly developed and commercialized by BioMarin; Naglazyme® (galsulfase) for MPS VI, a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for MPS I, a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Powder for Oral Solution and Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany and Firdapse® (amifampridine), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Product candidates include drisapersen, an exon skipping oligonucleotide, for which a marketing application has been submitted to FDA and EMA for the treatment of patients with Duchenne muscular dystrophy (DMD) with mutations in the dystrophin gene that are amenable to treatment with exon 51 skipping, pegvaliase (PEGylated recombinant phenylalanine ammonia lyase, formerly referred to as BMN 165 or PEG PAL), which is currently in Phase 3 clinical development for the treatment of PKU, talazoparib (formerly referred to as BMN 673), a poly ADP-ribose polymerase (PARP) inhibitor, which is currently in Phase 3 clinical development for the treatment of germline BRCA breast cancer, reveglucosidase alfa (formerly referred to as BMN 701), a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which is currently in Phase 3 clinical development for the treatment of Pompe disease, vosoritide (formerly referred to as BMN 111), a modified C-natriuretic peptide, which is currently in Phase 2 clinical development for the treatment of achondroplasia, BMN 044, BMN 045 and BMN 053, exon skipping oligonucleotides, which are currently in Phase 2 clinical development for the treatment of Duchenne muscular dystrophy (exons 44, 45 and 53), cerliponase alfa (formerly referred to as BMN 190), a recombinant human tripeptidyl peptidase-1 (rhTPP1) for the treatment of CLN2 disorder, a form of Batten disease, which is currently in Phase 1, BMN 270, an AAV-factor VIII vector, for the treatment of hemophilia A and BMN 250, a novel fusion of alpha-N-acetyglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2), for the treatment of MPS IIIB.

CONTACT: Investors: Traci McCarty BioMarin Pharmaceutical Inc. (415) 455-7558 Media: Debra Charlesworth BioMarin Pharmaceutical Inc. (415) 455-7451

Source:BioMarin Pharmaceutical Inc.