To build the "best pipeline in BioMarin history," the California biotech is looking to its already approved meds as a jumping-off point.
This June, the FDA cleared Roctavian as a one-time gene therapy for adults with severe hemophilia A. For BioMarin, that was just the start, with plans to expand within the hemophilia population to adolescents, for instance, or into the Japanese market. The same goes for Voxzogo, which snagged FDA approval in achondroplasia—a genetic disorder that impairs bone growth and is the most common form of disproportionately short height—in late 2021.
“The thing is, Roctavian and Voxzogo, they’re not one thing, they’re 10 things,” Hank Fuchs, M.D., BioMarin’s president of worldwide R&D, told Fierce Biotech in an interview.
BioMarin has since met with the FDA to discuss a pathway for Voxzogo in hypochondroplasia, a genetic disorder related to achondroplasia but with more subtle effects. The Big Biotech expects to launch a pivotal phase 3 trial in children with the condition later this year, Fuchs said. The drug's proven durability and safety make BioMarin’s late-stage pipeline much more stable.
And that will allow the company to take some new bets. BioMarin expects to increase the pace of investigational new drug (IND) applications to move the next wave of prospects into the clinic faster to grow the business more sustainably, Fuchs said. Currently, the company is tracking toward two new INDs filed each year, according to slides presented at an R&D day held Tuesday.
BioMarin used the presentation to roll out two new candidates, BMN 365 and BMN 355, which target areas of unmet need. 365 is for plakophilin-2 mutations and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Patients with the condition can suffer from irregular heartbeat and even sudden death. BioMarin is hoping to administer a replacement gene to form a protein that can help overcome the genetic deficiencies and, if successful, reverse irregular heartbeats, also known as arrhythmia, to restore cardiac function. Preclinical studies of the AAV-mediated protein gene therapy have demonstrated proof of concept, Fuchs said, and BioMarin is initiating IND-enabling studies over the next year.
The other new addition—355—is a monoclonal antibody for long-QT syndrome types 2 and 3, which is a deficiency that prevents appropriate electrical function in the heart and can lead to abnormal heart rhythms. Currently, no disease-modifying treatments exist for the condition. BioMarin hopes to launch a global trial for the preclinical candidate in 2025.
Meanwhile, BioMarin has two INDs expected by the end of the year for its existing pipeline, including BMN 349 for alpha-1 antitrypsin deficiency. The uncommon inherited disorder can cause lung disease and liver disease, and there's currently no standard of care for the liver disease. Fuchs said IND-enabling studies for the small-molecule candidate are wrapping up, and clinic entry is expected “imminently.”
BioMarin shared (PDF) preclinical data at the R&D day on AAV gene therapy BMN 293, which is expected to fuel initiation of human trials next year. The therapy is being developed for myosin binding protein C3 hypertrophic cardiomyopathy—a condition that can be treated using beta blocker medications, but BioMarin wants to improve symptomatic heart disease using just a single dose.
IND-enabling studies for BMN 351, a next-gen antisense oligonucleotide therapy for Duchenne muscular dystrophy, just wrapped up, and the findings are being submitted to health authorities.
BioMarin also has BMN 255, which recently wrapped up a phase 1 study in the challenging condition of nonalcoholic fatty liver disease (NAFLD), which can lead to nonalcoholic steatohepatitis.
BioMarin is tackling the tricky condition by looking at a subset of NAFLD patients that have serious comorbidities due to hyperoxaluria, a rare condition characterized by recurrent kidney stones. The launch of a pivotal phase 2/3 assessing the oral small molecule is currently underway.