By Andrea Schelhaas, Stephanie Meredith and Katie Stoll
In November 2021 under the Accelerated Approval Program, the U.S. Food and Drug Administration announced approval of Voxzogo (vosoritide), a drug developed by BioMarin for the purpose of increasing linear growth in children with achondroplasia with open growth plates (individuals who are actively growing). Achondroplasia is the most common form of skeletal dysplasia causing short stature. Achondroplasia results from a single change in the fibroblast growth factor receptor 3 (FGFR3) gene. Typically, the FGFR3 pathway works in unison with the c-type natriuretic peptide (CNP) pathway to regulate bone growth: FGFR3 slows bone growth when needed and the CNP pathway accelerates bone growth. Therefore, a single “gain of function” genetic change in the FGFR3 gene (increasing FGFR3 activity) affects the regulation of cartilage and bone growth in individuals with achondroplasia. Though children with achondroplasia grow every day, their rate of growth is slower than for the general population, leading to short stature. On average, individuals with achondroplasia reach an adult height of about 4 feet tall, though height is somewhat variable for each person and family.
Vosoritide is a CNP analog (performs a similar function to naturally occuring CNP) and was developed to counteract the effects of a FGFR3 mutation, with a year-long, double-blind randomized trial (RTC) showing an increase in growth (a mean of 1.57 cm/0.71 in per year) in participants who received the drug. A follow-up study has shown that this increased growth velocity is sustained over a two year period, but it is not yet known whether this increased growth velocity will actually lead to greater final adult height. In other words, it is unknown whether individuals who took this medication will be taller, or will just reach their adult height more rapidly than they would have without the medication. While some theorize that certain health complications associated with achondroplasia, including spinal compression and sleep apnea, may be ameliorated by the use of vosoritide, this is currently speculation. Instead, FDA approval of vosoritide was based on the trial’s primary endpoint, “change from baseline of annualized growth velocity,” not on proven medical benefit.
Little People of America (LPA), the largest patient advocacy organization for people with short stature, including achondroplasia, published a position statement on vosoritide, making it clear that this drug’s focus on growth velocity is “a pharmaceutical solution for a societal problem.” This statement references the social model of disability, which defines disability as created by societal and environmental barriers, rather than the physical characteristics or abilities of the individual. This model therefore makes the case that prioritizing research efforts that improve access to quality medical treatment, inclusive environments, and social support can counteract the barriers faced by people with achondroplasia. LPA has called for BioMarin and other researchers and pharmaceutical companies developing treatments for achondroplasia to focus on addressing priorities that are meaningful to the dwarfism community, such as reducing spinal stenosis, treating sleep apnea, medically beneficial surgeries, and other interventions that would improve quality of life.
Calls from dwarfism advocates seem mostly to have been ignored, and the relationship between pharmaceutical companies and the individuals they serve is often strained. Since the introduction of this medication into the global healthcare market, vosoritide has become the blockbuster drug in BioMarin’s portfolio. The price for a single year of treatment is $320,000 per person (approximately $900/dose, administered daily by injection) and BioMarin reported revenues of $735 million from vosoritide in 2024 alone. This treatment has been rapidly adopted into clinical practice despite it being unclear whether it will ultimately address the health issues that people with achondroplasia consider most important.
During the BioMarin 2024 Quarter 3 earnings call (taking place on October 29, 2024), the company’s chief commercial officer, Cristin Hubbard, announced anticipated “global guidelines” that would “recommend children with achondroplasia be referred as soon as a diagnosis is suspected to enable early initiation of treatment.”
And just as predicted, a few months later, the International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia were published in Nature Reviews Endocrinology. In the Ethics Declarations at the end of the document, it is noted that BioMarin provided financial support for the development of the guidelines, a clear conflict of interest. Moreover, a majority of the guideline author group (75%) disclosed financial affiliation with BioMarin. And while the author group did include representatives from two patient advocacy groups, they were representatives who had previously voiced support of this treatment. Notably, the guideline group did not include any representation from LPA or individuals with achondroplasia who have not pursued height altering interventions. LPA has made clear their concerns about BioMarin’s priorities in vosoritide development, stating “LPA strongly believes that a pharmaceutical intervention focusing on growth velocity is not addressing the actual health and quality of life issues of people with dwarfism. Our height-related challenges are primarily based on inaccessible architecture, lack of universal design, and society’s intolerance and discrimination of people with short stature. We are concerned that this recently approved drug attempts a pharmaceutical solution to a societal issue.”
Indeed, many people with achondroplasia do not view height as a medical problem to solve, and instead view it as an important aspect of one’s identity and community. It is worth clearly stating that people with achondroplasia grow to live full and independent lives irrespective of their stature. They have friends, participate in extracurricular activities, drive cars, go to college, date, get married, have children, and work in any number of careers.
About 80% of individuals with achondroplasia are born to average stature parents, meaning that most new and expectant parents of children with achondroplasia will not have lived experience or personal connections to inform decisions about vosoritide. Parents learning of a new diagnosis are likely to instead look online, and if they look to achondroplasia.com they will be inundated with content developed by BioMarin. On this site, people can search for providers including endocrinologists in their area who are familiar with vosoritide; however, these providers may not have experience in the medical management of children with achondroplasia or have connections with the dwarfism community to support families as they learn about living with achondroplasia and the various perspectives on treatments for increasing height.
And now BioMarin’s marketing has expanded beyond their digital and clinical presence to financing global practice guidelines developed by a biased selection of contributors who support the use of this medication. There is concern that this skewed representation has subsequently infused bias into the guidelines, and it is likely that this bias will be perpetuated through websites, presentations, and conversations in offices of obstetricians and pediatricians globally.
We believe that families considering treatment options for genetic conditions, including achondroplasia, deserve complete, unbiased information to make informed decisions. Healthcare providers must present comprehensive details about all available treatments and their potential outcomes, including how affected communities view treatments and how treatments may negatively impact quality of life through its effects on coping mechanisms, personal identity, and emotional health—which we do not know for vosoritide.
Additionally, people who have lived experience with achondroplasia offer invaluable insights into these complex psychosocial dynamics—having personally experienced identity development, community belonging, and social adaptation throughout their lives—and it is imperative that these voices are included and elevated in conversations about their own treatment. As the Disability rights movement reminds us, “Nothing about us without us” is more than a slogan; it’s a call to action that must shape the future of rare disease research and care.The BioMarin-funded guidelines suffer from a critical flaw: they exclude diverse perspectives from the achondroplasia community. This oversight is particularly problematic given the historical stigmatization faced by people with achondroplasia, leading quality of life assessments to often reflect misconceptions about short stature rather than lived experiences. Many studies have been funded by and/or authored by pharmaceutical companies including Biomarin, rely on biased methodologies, and draw on data primarily collected from clinical trial participants who actively sought height-increasing treatments—a narrow subset that does not necessarily represent the broader community’s views. Practice guidelines are intended to serve as medical consensus statements that guide providers less familiar with a condition, not as promotional tools funded and authored by pharmaceutical companies with clear financial motivations.
Creating truly ethical and inclusive treatment guidelines requires addressing these gaps through comprehensive community engagement. This means consulting with established advocacy organizations that operate independently of pharmaceutical interests, systematically including adults with achondroplasia from diverse socioeconomic backgrounds (both those who have pursued height-altering interventions and those who have not), and developing quality of life measures that distinguish genuine medical needs from limitations created by societal barriers.
Only through this inclusive approach can guidelines adequately address the complex realities faced by individuals with achondroplasia and support genuinely informed decision-making for families considering treatment options.