BioMarin Hits Bingo on Dwarfism and Hemophilia A Targets


The California based BioMarin Pharmaceutical acclaimed as one of the ‘World’s Most Innovative Companies’ by Forbes in 2015 hit on two significant diseases together. Biomarin ignited a new hope for children affected with dwarfism and hemophilia A.

biomarin pharmaceutical logoIts new drug vosoritide targeted to treat achondroplasia (the most common cause of dwarfism) has shown “durable and persistent” effects on dwarf children. On the other hand, its hemophilia A gene therapy treatment BMN 270 featured a promising result in its Phase I/II clinical trial.

Vosoritide molecular mechanism

Figure 1. Molecular mechanism of vosoritide. A; Chondrocyte with constitutionally active FGFR3 that down-regulates its development via the MAPK/ERK pathway. B; Vosoritide (BMN 111) blocks this mechanism by binding to the atrial natriuretic peptide receptor B (NPR-B), which subsequently inhibits the MAPK/ERK pathway at the RAF-1 protein. (Image credit: Florence Lorget et al. – “Evaluation of the Therapeutic Potential of a CNP Analog in a Fgfr3 Mouse Model Recapitulating Achondroplasia”. Am J Hum Genet 91 (6): 1108–1114. DOI:10.1016/j.ajhg.2012.10.014.)

According to BioMarin, 80% of children with achondroplasia are born of parents with normal stature. It further states that such a condition in these children resulted from a spontaneous gene mutation. Achondroplasia is the most common cause of dwarfism and is found in about one of 25000 live births or about 96000 potential patients. Apparently there are no licensed medications for the condition in Europe, the US, Latin America and the Middle East.

BioMarin is expecting to launch a Phase III study on children between 5 and 14 years of age at the end of 2016. Earlier in the Phase I and the Phase II studies scientists found the following results:

  • In the Phase I study it was found that during a six month trial patients experienced a 50% increase in their growth i.e. about 2 cm per year. Another group saw a 65% increase in growth i.e. 2.3 cm per year.
  • In the Phase II study, scientists discovered that patients saw 64% more growth or about 1.9 cm over a period of one year.

The adverse effects related to the drug were found to be moderate although injection site infections and decrease in blood pressure were noted.

We’re encouraged by the consistency of the data from six to 12 months in both safety and efficacy, and plan to initiate a Phase 3 study by the end of the year,” Hank Fuchs, MD, Chief Medical Officer at BioMarin said in a statement Wednesday. “By addressing the root cause of achondroplasia with vosoritide treatment and normalizing annualized growth velocity in children with achondroplasia, we ultimately hope to improve the medical complications of disproportionate bone growth.”

BioMarin’s Phase 1/2 clinical trial for hemophilia A gene therapy BMN 270 has produced encouraging data. According to BioMarin, it could potentially reduce or even completely eliminate the need for infusions of factor VII (a protein responsible for blood clotting). Out of the 8 patients who were suffering from hemophilia A and were treated with BMN 270, 6 who were given the highest dose improved from moderate ranges of the factor levels. In some cases normal range was also achieved.

We are encouraged by this early data on BMN 270 and the trend we are seeing in increasing Factor VIII levels over time. BMN 270 could have the potential to reduce and possibly eliminate the need for infusions of Factor VIII,” said Hank Fuchs, M.D., Chief Medical Officer at BioMarin.

BMN 270 has received orphan drug designation from the European Commission and U.S. Food and Drug Administration. Phase III design preparation and high volume manufacturing plans are underway.

“If BMN 270 allows hemophilia A patients to maintain around 5% of normal levels of Factor VIII, it could have a real and meaningful clinical benefit by reducing the need for Factor VIII infusions and spontaneous bleeds,” said John Pasi, Ph.D. F.R.C.P, Professor of Haemostasis and Thrombosis at Barts and the London School of Medicine and Dentistry and primary investigator for the BMN 270 Phase 1/2 clinical trial. “I am looking forward to further assessing the data over the 16 weeks and beyond in this ongoing study.”

The present clinical study on BMN 270 is a dose escalation study with the goal of observing an increase in factor VIII levels. Secondary endpoints include assessing the impact of BMN 270 on the frequency of factor VIII replacement therapy, the number of bleeding episodes requiring treatment and any potential immune responses. Patients will be monitored for safety and durability of effect for five years.

Let us see whether this novel treatment of Hemophilia A could get BioMarin its new blockbuster drug.

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