BioMarin Pharmaceutical operates as a global biotechnology company, concentrating on the development and commercialization of therapies for individuals living with rare and ultra-rare genetic diseases. A pharmaceutical pipeline includes drug candidates across various stages, from early research to advanced clinical trials and regulatory review. BioMarin’s pipeline reflects its ongoing commitment to addressing unmet medical needs and its future growth potential in specialized therapeutic areas.
Gene Therapy Programs
BioMarin has made substantial investments in gene therapy, particularly evident in its work on severe hemophilia A. Their leading gene therapy asset for this condition is valoctocogene roxaparvovec, marketed as Roctavian. This therapy aims to provide a sustained source of Factor VIII, the clotting protein deficient in individuals with hemophilia A, after a single infusion.
The mechanism of Roctavian involves the use of an adeno-associated virus serotype 5 (AAV5) vector. This modified virus delivers a functional copy of the Factor VIII gene to liver cells, enabling the body to produce its own Factor VIII protein. This approach seeks to reduce or eliminate the need for frequent intravenous Factor VIII infusions, which are the standard of care for many patients. Five-year data from the Phase 3 GENEr8-1 trial showed 81.3% of participants remained off prophylactic treatment, with mean Factor VIII activity levels in the mild hemophilia range.
Other gene therapy programs are also part of BioMarin’s early-stage pipeline, targeting different genetic conditions. For instance, the company has preclinical programs exploring AAV gene therapies for conditions such as myosin binding protein C3 hypertrophic cardiomyopathy and plakophilin-2 (PKP2) arrhythmogenic cardiomyopathy. These programs demonstrate the broader application of gene therapy technology beyond hemophilia.
Enzyme and Small Molecule Therapies
Beyond gene therapy, BioMarin maintains a diverse portfolio that includes established and developing enzyme replacement therapies and small molecule drugs. These treatments address various rare genetic disorders through distinct biological mechanisms. Enzyme replacement therapies typically involve providing a missing or deficient enzyme to restore normal metabolic function.
An example of an enzyme replacement therapy is Vosoritide, known as Voxzogo, which targets achondroplasia, a common form of dwarfism. This peptide analog of C-type natriuretic peptide (CNP) works by counteracting overactive fibroblast growth factor receptor 3 (FGFR3) signaling, promoting bone growth by stimulating chondrocyte proliferation and differentiation in growth plates. Another enzyme therapy, Palynziq (pegvaliase-pqpz), treats Phenylketonuria (PKU) in adults who have uncontrolled blood phenylalanine concentrations. Palynziq substitutes the deficient phenylalanine hydroxylase (PAH) enzyme with a PEGylated version of phenylalanine ammonia lyase, which breaks down phenylalanine into other compounds.
BioMarin’s enzyme therapy portfolio also includes treatments for lysosomal storage diseases, such as Vimizim for Morquio A syndrome and Naglazyme for mucopolysaccharidosis VI (MPS VI). The recent acquisition of Inozyme Pharma further expanded this area with INZ-701, a late-stage enzyme replacement therapy for ENPP1 Deficiency, a rare genetic condition affecting blood vessels, soft tissues, and bones. This acquisition aims to bring a potential first-in-disease treatment for this condition, with pivotal data expected in early 2026.
Investigational and Early-Stage Research
BioMarin’s pipeline includes a range of investigational and early-stage research programs focused on future therapeutic advancements. These programs are in preclinical or early clinical phases, typically Phase 1 or Phase 2, exploring new modalities and disease targets. The company is directing efforts toward conditions within central nervous system disorders, cardiovascular diseases, musculoskeletal/metabolic conditions, and non-oncology hematology.
The early-stage pipeline includes candidates like BMN 349 for alpha-1 antitrypsin deficiency (AATD)-associated liver disease, a small molecule candidate currently wrapping up IND-enabling studies. Another program, BMN 351, is an exon 51 oligonucleotide being developed for Duchenne muscular dystrophy. BioMarin also has BMN 333, a program targeting multiple growth disorders beyond achondroplasia. These programs represent the company’s commitment to expanding its therapeutic reach and exploring novel mechanisms for rare genetic conditions.
Recent Regulatory Milestones and Updates
BioMarin has experienced several significant regulatory milestones and updates concerning its pipeline assets. Roctavian (valoctocogene roxaparvovec) for severe hemophilia A received conditional marketing authorization from the European Commission in August 2022. Subsequently, the U.S. Food and Drug Administration (FDA) approved Roctavian in June 2023, making it the first gene therapy for adults with severe hemophilia A. The FDA’s approval followed a resubmission of the Biologics License Application (BLA) in October 2022, after an initial rejection in 2020 due to a request for additional follow-up data.
The company has also focused on expanding indications for existing therapies. Voxzogo (vosoritide) is being evaluated for hypochondroplasia, a genetic disorder related to achondroplasia, with a pivotal Phase 3 trial in children with the condition expected to be launched. In April 2025, BioMarin announced positive pivotal data for Palynziq (pegvaliase-pqpz) in adolescents with phenylketonuria from the Phase 3 PEGASUS trial. This data supports the potential expansion of Palynziq’s use to a younger patient population.