New drug shown to improve bone growth in children with achondroplasia


Date:
September 8, 2020
Source:
Murdoch Childrens Research Institute
Summary:
A phase three global clinical trial has shown that the drug
vosoritide restores close-to-average bone growth rates of children
with achondroplasia, the most common form of dwarfism. The study
enrolled 121 children aged five to 18. The 60 children who received
vosoritide grew an average 1.57 cm more per year. Regulatory
authorities are reviewing applications to license treatment.



FULL STORY ==========================================================================
A phase three global clinical trial led by the Murdoch Children's
Research Institute (MCRI) has shown a new drug boosts bone growth in
children born with achondroplasia, the most common type of dwarfism.


==========================================================================
The randomised, double-blind, placebo-controlled trial results, led by
MCRI clinical geneticist Professor Ravi Savarirayan, have been published
today in the medical journal, The Lancet.

Achondroplasia is the most common cause of dwarfism and is caused by overactivity of the FGFR3 protein, which slows bone growth in children's
limbs, spine, and the base of their skull.

The experimental drug, vosoritide, blocks the activity of FGFR3,
potentially returning growth rates to normal. Previous MCRI-led
trials have confirmed vosoritide was safe to give to young people with dwarfism. This new randomised controlled trial conclusively shows it is
also effective increasing bone growth over one year of daily injections.

Professor Savarirayan said, "This drug is like releasing the handbrake on
a car, it lets you get up to full speed instead of having to drive with
the brakes on." Achondroplasia is a genetic bone disorder affecting
250,000 people worldwide, or about one in every 25,000 children. It is
caused by a mutation in the FGFR3 gene that impairs bone growth and means
that children grow around 4 cm per year, instead of the usual 6 to 7 cm.



========================================================================== Current achondroplasia treatments, like surgery, only address the
symptoms. In contrast, vosoritide is a precision therapy directly targeted
at the molecular cause of the disease.

BioMarin Pharmaceutical, who manufacturers the peptide drug and funded
the trial, has applied to the US Food and Drug Administration to license vosoritide for its use in treating achondroplasia. The European Medicines Agency validated the Company's application. Australian licensing is
expected to follow sometime after a successful US application.

For the trial, 121 children aged five to under 18 were enrolled,
which was conducted at 24 hospitals in seven countries. In Melbourne,
the trial was conducted at the Melbourne Children's Trial Centre. The
60 children who received daily injections of vosoritide grew an average
of 1.57 cm per year more than the children who received placebo, which
brought them almost in line with their typically developing peers.

Professor Savarirayan said, "We know that beyond the cold hard facts
and figures around growth rates and bone biology, we have hope that
a treatment can improve kids' health outcomes, social functioning and
increase access to their environments. Anecdotally, our patients tell
us they now are able to do more stuff like climbing trees, jumping
rocks and being more independent generally, which is specific to their experiences." Dr Johnathon Day, Medical Director of Clinical Science at BioMarin Pharmaceutical Inc. said, "Vosoritide is the first potential
precision pharmacological therapy that addresses the underlying cause
of achondroplasia and this randomized, double-blind, placebo-controlled
Phase 3 study further adds to the scientific knowledge we've gained
over many years from the clinical development program. I'd like to
personally thank and congratulate all of the investigators and I am
especially grateful to all of the children and their families who have participated in these studies," Paul Cohen and Elizabeth Ryan's daughter, Sarah, was born with achondroplasia.

Sarah was one of the very first patients enrolled in the trial. Mr
Cohen said, "During the trial we've seen Sarah grow up at the same rate
as her friends. She can now join in bike rides with her friends, and
loves being allowed on our local waterslide." Although the trial did
not significantly improve the children's proportions between their upper
and lower bodies, the children will be followed until they achieve their
final adult height to see how long the drug's effects last and whether
they experience a growth spurt during puberty, as this doesn't normally
happen in children with achondroplasia.

Vosoritide is also being tested in children from birth to five years
which may improve final height, body proportion and other age-related complications such as spinal cord compression, which can cause sudden
death.


========================================================================== Story Source: Materials provided by
Murdoch_Childrens_Research_Institute. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Ravi Savarirayan, Louise Tofts, Melita Irving, William Wilcox,
Carlos A
Bacino, Julie Hoover-Fong, Rosendo Ullot Font, Paul Harmatz, Frank
Rutsch, Michael B Bober, Lynda E Polgreen, Ignacio Ginebreda,
Klaus Mohnike, Joel Charrow, Daniel Hoernschmeyer, Keiichi Ozono,
Yasemin Alanay, Paul Arundel, Shoji Kagami, Natsuo Yasui, Klane K
White, Howard M Saal, Antonio Leiva-Gea, Felipe Luna-Gonza'lez,
Hiroshi Mochizuki, Donald Basel, Dania M Porco, Kala Jayaram,
Elena Fisheleva, Alice Huntsman- Labed, Jonathan Day. Once-daily,
subcutaneous vosoritide therapy in children with achondroplasia:
a randomised, double-blind, phase 3, placebo-controlled,
multicentre trial. The Lancet, 2020; 396 (10252): 684 DOI:
10.1016/S0140-6736(20)31541-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200908093744.htm

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