Scientists have come up with a drug, injected once a day, that appears to make children’s bones grow. To many, it’s a wondrous invention that could improve
the lives of thousands of people with dwarfism. To others, it’s a profit-driven solution in search of a problem, one that could unravel decades of hard-won
respect for an entire community.
In the middle are families, doctors, and a pharmaceutical company, all dealing with a philosophically fraught question: Is it ethical to make a little
The most common cause of dwarfism is known as achondroplasia. People with the condition, caused by a rare genetic mutation, have shorter limbs and shorter
stature than those without it, and they deal with a lifetime of skeletal issues that often require a battery of corrective surgeries. For years a U.S. company called BioMarin Pharmaceutical (
has been developing a drug that targets the genetic roots of achondroplasia, a mutation that stops cartilage from turning into bone. The goal, according
to the company, is to prevent the medical complications associated with achondroplasia, which include sleep apnea, hearing loss, and spinal problems.
But proving the drug’s long-term skeletal benefits would require a decades-long study, which is an expensive and, to BioMarin, impractical proposition.
Instead, the company is measuring the the most immediate byproduct of bone growth: height.
And that’s where the philosophical schism begins.
For thousands of little people, the short stature that comes with achondroplasia is not a disability in need of treatment but a difference to be celebrated.
Organizations like Little People of America have spent years dispelling stereotypes, advocating for fairness, and pointing out that having achondroplasia
doesn’t preclude anyone from a fulfilling life. Dwarf pride means flourishing because of one’s body, not in spite of it.
Through that lens, the drug looks to some like a threat of erasure, a so-called cure for people who are not sick. Furthermore, about 80% of babies with
achondroplasia are born to parents of average height. That means, if the drug goes on to win Food and Drug Administration approval, the decision of whether
to give it to a child would often be made by people with no exposure to little people culture, who know nothing of dwarf pride.
“People feel like this is an effort to eliminate the dwarfism community,” said Becky Curran Kekula, a disability advocate and motivational speaker who
was born with achondroplasia. “Some say this is going to help things get better, but how could someone know?”
There is no consensus. Where some little people see the drug, called vosoritide, as an affront to their identity, others wish it had existed when they
were children. Parents, too, speak of it either as a source of hope or a danger to their child’s sense of self-worth. Online discussions of the issue often
grow heated. Some people contacted by STAT declined to speak on the record for fear of inciting a backlash.
There is, however, little dispute over what the future holds. Vosoritide is on track to win FDA approval, leaving all parties to prepare for a world in
which height is a matter of choice.
BioMarin’s work in dwarfism starts with the genetics.
In 1994, scientists at the University of California in Irvine traced achondroplasia to
a gene called FGFR3,
which regulates bone growth. In people with the condition, they discovered, that gene is mutated, impairing the natural process of turning cartilage into
About seven years later, researchers at Kyoto University in Japan demonstrated that a protein in the body, long studied for its role in heart function,
seemed to reverse the effects
of that broken gene. The natural version of that protein, called C-type natriuretic peptide, gets cleared out of the body in about a minute, making it
useless as a medicine. But, over about a decade of scientific trial and error, BioMarin came up with an analog called CNP39, a longer-lasting version that
it believed could counteract the genetic mutation and restore healthy bone growth. The result was vosoritide.
Do large pharma companies provide drug development innovation? Our analysis says no
So far, the drug looks like it works. In a clinical trial enrolling 35 children with achondroplasia, the highest doses of vosoritide helped kids reach
growth milestones 50% faster than they did without treatment. Compared to baseline, those children grew roughly two extra centimeters each year, bringing
them nearly in line with their average-heighted peers. The side effects were mostly mild, including irritation at the injection site, low blood pressure,
and fever. The results were published
in the New England Journal of Medicine
BioMarin started a larger, placebo-controlled study in 2016, enrolling more than 100 children between 5 and 14 in a trial expected to conclude later this
year. If it’s positive, the company will submit the results to the FDA in hopes of winning approval. As before, the primary goal is increasing growth.
“But aspirationally, what we’re all hoping to see is not only do we increase height but we improve the quality of life and the clinical morbidities that
these patients suffer from,” said Dr. Jonathan Day, BioMarin’s executive medical director.
Achondroplasia affects the growth of all but a few bones in the body, not just the ones associated with height. That means vosoritide’s benefits, while
most observable in terms of height, would in theory translate to the spine, where achondroplasia’s most dangerous side effects take root.
That will take years to prove, Day acknowledged. He has heard the concerns about the emphasis on height, about the existential implications for adult little
people. But vosoritide, he argued, presents the best chance of a better future for children with achondroplasia.
“We can’t make a drug that enhances skeletal growth but doesn’t make you taller,” Day said. “It just doesn’t work that way.”
“People feel like this is an effort to eliminate the dwarfism community. Some say this is going to help things get better, but how could someone know?”
BECKY CURRAN KEKULA, DISABILITY ADVOCATE AND MOTIVATIONAL SPEAKER WHO WAS BORN WITH ACHONDROPLASIA
Little People of America, with a membership of around 8,000, spent years keeping BioMarin at a distance. Founded in 1957, the group’s stated mission is
to provide a safe, welcoming community for all little people, no matter their opinions on controversial issues like dwarf tossing and limb-lengthening
surgery. When the group learned about vosoritide in 2012, it seemed like yet another matter of personal choice, something on which members could disagree
but from which the group would officially abstain.
But LPA’s commitment to neutrality came dramatically into question earlier this year, when the group’s board invited representatives from BioMarin to the
organization’s annual conference and, most alarming to some members, accepted a $130,000 donation from the company.
Many members only learned of the arrangement when they saw the drug company’s logo on a list of LPA sponsors on conference collateral. That led to an outpouring
of concern and condemnation on
LPA’s Facebook (
page. At the conference, held in San Francisco in July, the group convened an emergency town hall meeting, where the board sat in a hotel ballroom and
listened to outrage and confusion from its members. Footage of that meeting was also posted to the Facebook page.
“Seeing that sponsorship on the conference booklet was like a slap in my face,” LPA member Monique Conley told the board. “We didn’t need their money,”
she said to applause. “We’re not these poor charity cases. We have lives. We love our lives.”
Regardless of LPA’s intentions, its acceptance of money from BioMarin sent the message to some members that the group had co-signed the development of
vosoritide, a notion many find abhorrent, said Olga Marohnic, chairwoman of the organization’s Hispanic affairs committee.
“There’s millions of other companies that we can get money from that will not tie us to a pharmaceutical company that in my view is trying to tell my family,
tell my son, and my friends that they’re not OK the way they are,” Marohnic said at the town hall. Her teenage son, Matthew, has achondroplasia.