BioMarin Pharmaceutical shared some amazing news last week when they revealed that their new experimental drug to treat dwarfism showed a 50% growth increase among the children receiving the highest doses in a preliminary study. The drug, called BMN 111, or Vosoritide, is vying to be the first ever drug approved to treat dwarfism. More specifically, it treats achondroplasia, the most common form of dwarfism.
“We are very encouraged to have observed evidence of activity with vosoritide in children participating in our Phase 2 study,” said Wolfgang Dummer, M.D., Ph.D., Vice President, Clinical Development of BioMarin, in a press release. “In children receiving the highest dose of 15 micrograms per kilogram daily, we observed a 50% increase in mean annualized growth velocity compared to their own natural history control growth velocity. This increase in growth velocity, if maintained, could allow children with achondroplasia to resume a normalized growth rate.”
Drummer adds that “vosoritide was well tolerated in all dose cohorts and we have observed no major safety concerns to date.” According to the press release, “The majority of [adverse effects] reported were mild (Grade 1) and included injection site reactions, headache, hypotension, back pain and cough.”
In a conference call, BioMarin’s chief medical officer, Dr. Henry J. Fuchs, said “I don’t think we could have asked for a better outcome than we shared with you today.”
Of course, this was just a preliminary study, so it is important not to get too excited. From the New York Times:
Dr. William R. Wilcox, a human genetics professor at Emory University, called the results “promising.” But he expressed caution, given that only 10 children were getting the high dose and were treated for only six months.
“Six-month results are important, but they don’t really give you the whole story,” said Dr. Wilcox, who has been a consultant to BioMarin.
He said that human growth hormone, a drug already marketed for certain children, can also increase the growth rate for people with dwarfism to 6 centimeters per year — but the effect wears off after one year. So, he said, it would be important to see if the BioMarin drug can increase growth year after year.
Dr. Dummer says BioMarin plans to “move into pivotal registration study discussions with health authorities with a dose of 15 micrograms per kilogram daily,” which is the maximum dose included in the preliminary study. He adds that they hope to try doubling the dosage in some instances: “In addition, to support further exploration of a dose that may enable ‘catch-up’ growth in the event of delayed treatment, we intend to study 30 micrograms per kilogram daily in ancillary studies.”
“We are looking forward to working with health authorities worldwide as we continue to develop vosoritide for patients with achondroplasia globally,” said Jean-Jacques Bienaimé, Chairman and Chief Executive officer at BioMarin. “It is estimated that about 96,000 patients in our established territories are afflicted with achondroplasia, so approximately 25%, or 24,000, are under 18 years of age and in our addressable market.”
The Times again:
[BioMarin] also intends to test the drug in children younger than 5, the lower age limit for the existing study. And the company is planning a Phase 3 trial that could potentially lead to the drug’s approval. That trial, executives said, could involve 50 to 100 children for a year.
The announcement wasn’t received well by everyone, as some regard dwarfism as a condition that does not require a “cure.” But achondroplasia can often lead to a host of medical issues that it seems most people would hope their child could avoid if possible. According to the BioMarin press release,
Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis, recurrent ear infections and obesity. Some of these complications can result in invasive surgeries such as spinal cord decompression and straightening of bowed legs. Some people with achondroplasia suffer from chronic pain and regularly confront a world not built for them….The worldwide incidence rate of achondroplasia is about one in 25,000 live births, per the World FactBook 2014 edition which translates into approximately 96,000 potential patients. The initial opportunity is about 25 percent of the incidence number because vosoritide is being tested in children whose growth plates are still ‘open,’ typically those under 18 years of age.”
For those interested in technical information on how the drug works, BioMarin shared this information about vosoritude (BMN-111) on their website:
Achondroplasia is the most common form of dwarfism. Achondroplasia is a result of an autosomal dominant mutation in the fibroblast growth factor receptor 3 gene (FGFR3), which causes an abnormality of cartilage and bone formation. In normal circumstances, FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones…
To counteract the effects caused by the activating FGFR3 mutation, BioMarin has developed a stabilized version of C-type natriuretic peptide (BMN-111), a natural human peptide that is a positive regulator of bone growth. BMN-111 binds to its own receptor which initiates intracellular signals that ultimately inhibit the overactive FGFR3 pathway. Daily subcutaneous injections of BMN-111 in mouse models of the disease have demonstrated the ability of this drug to correct the dwarf phenotype.
Amazing. Time to buy some BioMarin stock!
Read the full BioMarin press release here.