The world’s first achondroplasia drug

BioMarin is a global biotechnology company dedicated to developing and commercializing innovative therapies for patients with severe and life-threatening rare and ultra-rare genetic diseases. Its product portfolio includes seven commercial products and a variety of clinical and pre-clinical product candidates. The company recently announced the final positive results of a global phase III study of vosoritide (BMN111) in children with achondroplasia. The company announced that, based on recent meetings with us and European regulators, it plans to submit a marketing application for vosoritide to the US Food and Drug Administration (FDA) and the European medicines agency (EMA) in the third quarter of 2020.

Cartilage hypoplasia is the most common type of short-limb dwarfism. It is an autosomal dominant genetic disease. Globally, it affects the lives of 250,000 people. This disease can cause severe cardiovascular, neurological and metabolic complications. Cartilage hypoplasia is caused by mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3). FGFR3 is a negative regulator of bone development, which can affect the proliferation and differentiation of chondrocytes. Currently, there are no approved therapies to treat this disease. Vosoritide developed by BioMarin is a C-type natriuretic peptide (CNP) analog derived from natural human peptides. Natural human peptides are positive regulators of bone growth and development. Vosoritide inhibits the overactive FGFR3 signaling pathway by binding to specific receptors.

Vosoritide has previously been approved as an orphan drug for achondroplasia. If approved, vosoritide would be the first drug to treat achondroplasia in the United States and the European Union. The marketing application for vosoritide will be based on the results of a global phase III study and will be further supported by long-term safety and efficacy data from a phase II study, multiple ongoing extended studies, and extensive natural disease history data.

Achondroplasia is the most common form of disproportionately short stature. The study was a randomized, double-blind, placebo-controlled phase III study that assessed the efficacy and safety of vosoritide versus placebo in 121 children with achondroplasia aged 5-14 years with growth plates still open. These patients completed a baseline study for at least 6 months to determine their respective baseline growth rates before entering the phase III study. In the phase III study, patients were randomized to receive either vosoritide (15ug/kg/ day) or placebo for 52 weeks. The primary endpoint was the change in growth rate relative to baseline during the one-year treatment period in children treated with vosoritide compared to placebo.

The results showed that the study reached the primary endpoint: one year after treatment, the placebo-corrected growth rate of vosoritide treatment changed from baseline by 1.6 cm / year (p <0.0001). This result is consistent with the results in the large patient population studied. In the study, vosoritide was generally well tolerated and there was no clinically significant drop in blood pressure.

In mid-November 2019, patients with achondroplasia aged 5 to 14 years participated in this Phase 2 clinical study. The test results showed that compared with the height data of patients with natural history, vosoritide made the patients grow an average of 9 cm in the 54-month study, which reached a statistically significant difference. In addition, in the past 12 months alone, patients receiving vosoritide have grown 2.2 cm taller, further proving the therapeutic potential of vosoritide.

“Our natural history database has about 13,000 data points related to height. By comparing data from patients with a natural history, we have more information to support this treatment, demonstrating that vosoritide can significantly and consistently improve patient growth. BioMarin ’s Global R & D President Hank Fuchs, MD, said, “We have been working with regulatory agencies throughout the design and development of clinical projects and look forward to continued interaction in evaluating the safety and effectiveness of vosoritide in the treatment of childhood achondroplasia. We believe that we have a powerful data package, including global phase III studies, long-term results of open-label phase II studies, and extensive data on natural disease history over the same period. We are very grateful to the children and families who participated in these studies. They are contributing to more scientific data on potential treatments for achondroplasia. ”

The investigator of the vosoritide clinical project, John a. Phillips, MD, Vanderbilt University Medical Center, said: “vosoritide has the potential to be the first treatment for the root cause of achondroplasia. This will be a major breakthrough in medicine, It will provide doctors with a new tool to treat achondroplasia. As a therapist, I look forward to therapeutic interventions that go beyond treating symptoms, which will have a lasting positive impact on children with achondroplasia. ”


BioMarin Plans Regulatory Submissions for Marketing Authorization of Vosoritide to Treat Children with Achondroplasia in 3Q 2020 in both US and Europe