Biomarin

BACKGROUND: Phenylketonuria (PKU) is characterized by a deficiency in phenylalanine hydroxylase (PAH) that may lead to elevated blood phenylalanine (Phe) and significant neurocognitive and neuropsychological comorbidities. Pegvaliase (PALYNZIQ®, BioMarin Pharmaceutical Inc.) is a PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), which converts Phe to trans-cinnamic acid and ammonia, and was approved in May 2018 in the United States and in May 2019 in the European Union for decreasing blood Phe levels in adults with PKU with blood Phe levels >600 μmol/L...

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The investigation of new alternatives for disease prevention through the application of findings from dietary and food biotechnology is an ongoing challenge for the scientific community. New nutritional trends and the need to meet social and health demands have inspired the concept of functional foods and nutraceuticals which, in addition to their overall nutritional value, present certain properties for the maintenance of health. However, these effects are not universal. Nutrigenetics describes how the genetic profile has an impact on the response of the body to bioactive food components by influencing their absorption, metabolism, and site of action...

BACKGROUND: Ranibizumab and aflibercept are FDA-approved treatments for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Although these agents differ in cost and labeled dosing, it is unclear whether these differences are reflected in clinical practice. OBJECTIVE: To compare the real-world frequency and cost of ranibizumab and aflibercept injections among treatment-naive and previously treated patients with nAMD and DME...

BACKGROUND: Adeno-associated virus (AAV)-mediated gene therapy is under investigation as a therapeutic option for persons with hemophilia A. Efficacy and safety data include 3 years of follow-up after a single administration of AAV5-hFVIII-SQ. METHODS: We report durable efficacy, long-term safety, and clinical and biologic results in 15 adults with severe hemophilia A (factor VIII level, ≤1 IU per deciliter) who had received a single infusion of AAV5-hFVIII-SQ at various dose levels...

New England Journal of Medicine, Volume 382, Issue 1, Page 29-40, January 2020.

In May 2019, China National Medical Products Administration approved the marketing of an elosulfase alfa injection (brand name: Vimizim) from BioMarin Pharmaceutical for the treatment of patients with mucopolysaccharidosis (MPS) type IVA. This is the first drug to treat MPS in China, and it has ended the "dearth of medicines" to treat MPS in China, a situation that has persisted for many years. One can reasonably say that the drug has benefited from the continuous reform of the drug review and approval system in China and the increasing attention paid to rare diseases...

BACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia...

While one-time gene replacement therapies may offer transformative innovation for the management of ultrarare, health-catastrophic diseases, they also pose challenges to the current U.S. health care system. Historically, the United States and other countries have demonstrated a willingness to support higher prices for health gains in rare diseases. However, payers may be ill-prepared to address reimbursement based on single administrations associated with gene therapies. As yet, there is no consensus on how to appropriately reward gene therapy innovation...

BACKGROUND: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy. METHODS: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study...

OBJECTIVE: In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase. METHODS: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria...

BioMarin Pharmaceutical is developing pegvaliase (PALYNZIQ™) as a treatment for phenylketonuria, a genetic disorder caused by deficiency of phenylalanine hydroxylase which leads to neurotoxic accumulation of phenylalanine. Data from the phase III PRISM clinical trial program indicate treatment with pegvaliase is associated with sustained reductions in blood phenylalanine levels and sustained improvements in neurological sequelae in patients with phenylketonuria. Based on these positive results pegvaliase was recently approved in the US for adults with phenylketonuria who have uncontrolled blood phenylalanine concentrations on current treatment...

BACKGROUND: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4 ) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC...

BACKGROUND: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children. METHODS: In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years...

BACKGROUND: Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. METHODS: We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A...

Cerliponase alfa (Brineura™) is a recombinant human tripeptidyl peptidase-1 (TPP1) being developed by BioMarin Pharmaceutical Inc. for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1. CLN2 is characterised by progressive impairment of motor function, language deficiencies, seizures, ataxia, blindness and early death, and intracerebroventricular infusion of cerliponase alfa has been shown to reduce the progression of functional decline...

BACKGROUND: A Duchenne muscular dystrophy (DMD) cohort was identified using a claims-based algorithm to estimate health care utilization and costs for commercially insured DMD patients in the United States. Previous analyses have used broad diagnosis codes that include a range of muscular dystrophy types as a proxy to estimate the burden of DMD. OBJECTIVE: To estimate DMD-associated resource utilization and costs in a sample of patients identified via a claims-based algorithm using diagnosis codes, pharmacy prescriptions, and procedure codes unique to DMD management based on DMD clinical milestones...

Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (Kyndrisa™; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016...

BACKGROUND: Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited. METHODS: Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed...

BACKGROUND: Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease characterized by an absence or marked reduction of lysosomal N-acetylgalactosamine-4-sulfatase activity. Affected individuals have widespread accumulation of unmetabolized glycosaminoglycan substrates leading to detrimental effects. Recombinant human N-acetylgalactosamine 4-sulfatase (rhASB) is an approved enzyme replacement therapy for patients with MPS VI. Despite the known efficacy of weekly 4-h rhASB infusions, some clinicians wish to treat patients using reduced infusion times...