Tag Archive for: hypochondroplasia

Dr. Andrew Dauber measures Mia's height

First global clinical trial achieves promising results for hypochondroplasia

Dr. Andrew Dauber measures Mia's height

Trial participant Mia Maric is measured by Dr. Andrew Dauber.

Researchers from Children’s National Hospital presented findings from the first clinical trial of the medication vosoritide for children with hypochondroplasia – a rare genetic growth disorder. The results were presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting.

The big picture

Recently approved to increase linear growth and open growth plates in children with achondroplasia, vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation by inhibiting the ERK1/2-MAPK pathway.

“Vosoritide directly targets the pathway in the growth plate that is affected by the genetic mutation causing hypochondroplasia,” said Andrew Dauber M.D., M.M.Sc., chief of Endocrinology at Children’s National and lead author of the study.

During the phase 2 trial, researchers found vosoritide increased the growth rate in children with hypochondroplasia, allowing them to grow on average an extra 1.8 cm per year.

The patient benefit

Ivan Maric’s 11-year-old daughter, Mia, has been participating in the trial for the last 18 months. In 2022, they moved from Croatia to be part of the study.

“This has been life-changing for Mia,” Maric said. “Soon after receiving the initial doses, we immediately noticed growth. Now, she can independently manage everyday tasks such as washing her hair and reaching the sink to wash her hands.”

What’s next

Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions that interact with the ERK1/2-MAPK pathway.

“This study provides a proof of principle that this medicine will work for these children and supports further research in this area,” said Dr. Dauber. “I was excited to see how well tolerated the medication was and how some patients had excellent responses.”

This clinical trial funded by BioMarin is the first-of-its-kind to treat children with genetic short stature who do not have achondroplasia. Other growth-related conditions included in this phase 2 trial were Noonan syndrome, NPR2 mutations and Aggrecan mutations.

Additional authors from Children’s National: Anqing Zhang, Ph.D., Roopa Kanakatti Shankar, M.D., Kimberly Boucher, R.N., Tara McCarthy, B.A., Niusha Shafaei, B.A., Raheem Seaforth, B.A., Meryll Grace Castro, M.S., and Niti Dham, M.D.

two balls -- one with a sad face and one with a happy face

Understanding quality of life for children with hypochondroplasia

two balls -- one with a sad face and one with a happy face

Children with hypochondroplasia have low parent-reported quality of life (QOL) scores, according to findings from researchers at Children’s National Hospital.

Children with hypochondroplasia have low parent-reported quality of life (QOL) scores, according to findings from researchers at Children’s National Hospital. The data, presented as part of a poster presentation at the Pediatric Endocrine Society (PES) annual meeting, also found older age and shorter height may further exacerbate effects on QOL.

Hypochondroplasia is a skeletal dysplasia that has an estimated prevalence of 1 in 15,000-40,000 births and is characterized by short stature and disproportionately short arms, legs, hands and feet.

Participants of the study were 13 prepubertal boys ages 3-11 and 13 prepubertal girls ages 3-10, all with height z-scores < -2.25 SD and genetically proven hypochondroplasia.

Moving the field forward

Effective medications for growth in patients with hypochondroplasia are limited. Children’s National is participating in an ongoing study of a new drug, vosoritide, used to treat children in this population and will compare pre- and post-intervention QOL scores.

How will this work benefit patients?

Understanding QOL of children with hypochondroplasia will help clinicians provide better care and support.

“Knowing how a medication affects QOL will help guide counseling about use of this medication,” says Nicole Rangos, M.D., pediatric resident at Children’s National and lead author of the study.

Dr. Rangos received the Human Growth Foundation Award for best growth-related abstract at the PES annual meeting in May 2023. The award was established in 2007 to encourage fellows training in pediatric endocrinology to pursue clinical and bench investigations that may lead to a better understanding of human growth.

 

doctor measuring girl's height

Vosoritide shows promise for children with certain genetic growth disorders

doctor measuring girl's height

This is the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature, including hypochondroplasia, Noonan syndrome, NPR2 mutations and Aggrecan mutations.

Andrew Dauber, M.D., M.M.Sc., endocrinologist at Children’s National Hospital, presented preliminary results from a phase II clinical trial of a new drug, vosoritide, used to treat children with certain growth disorders, at the Pediatric Endocrine Society annual meeting held virtually on May 1.

Vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway.

This is the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature, including hypochondroplasia, Noonan syndrome, NPR2 mutations and Aggrecan mutations.

To date, 34 participants have enrolled in the trial with a median baseline height of -3.2 SD (interquartile range (IQR) -3.7, -2.6). 18 subjects have initiated on vosoritide and twelve have completed six months of therapy. The authors note that the mean increase in annualized growth velocity (AGV) was 1.8 cm/yr for subjects with hypochondroplasia and 6.1 cm/yr for subjects with Noonan syndrome or NPR2 mutations. The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr, while the two subjects with Noonan syndrome had increased in AGVs of 7.5 and 3.3 cm/yr. One of the Noonan syndrome subjects was previously treated with growth hormone (GH) for 2 years and AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the trial 6-month observation period and 11.6 cm/year during the first six months of vosoritide treatment.

To the researchers, the safety profile is quite reassuring. So far, the preliminary results showed increased growth in all the genetic subgroups with the patients with hypochondroplasia demonstrating a response similar to that seen previously in patients with achondroplasia. While the results are very promising for patients with Noonan syndrome and NPR2 mutations, the clinical trial must be completed before drawing further conclusions. The experts also plan to submit the study to a peer-reviewed journal in the future to validate the findings.

The big picture

This is the first medication that directly targets the pathway in chondrocytes (cells in the growth plate that make the bones grow longer) affected by these specific mutations. This means that the novel approach may give patients additional therapeutic options outside of growth hormone.

Why we’re excited

“These are the first patients in the world to ever receive this medication for their conditions,” said Dr. Dauber. “The results are very promising and may change the way we practice medicine. Patients have come from all over the world to participate in the study.”

Children’s National leads the way

This clinical trial funded by BioMarin is the first of its kind to treat children with genetic short stature who do not have achondroplasia. Children’s National is the only site in the world offering this therapy for patients with these conditions.

Find out more about the trial here.

little girl measuring her height

Study may change treatment of childhood growth disorders

little girl measuring her height

A new Phase 2 study at Children’s National will look at using the drug vosoritide to promote growth in children with growth disorders.

A child’s growth is often measured by pediatricians during routine physicals to identify abnormalities of growth and stature. An abnormality in these measurements could mean a child has a growth disorder. There are many different causes of growth disorders. Some can be the result of defects in genes related to the growth plate, which is the tissue near the end of long bones that grows as the child grows. Children with a growth disorder can present many different symptoms including short stature, joint pain, heart problems, bone problems and developmental delays. Scientists still have a lot to learn about what exactly causes these genetic growth disorders and treatments are limited, especially in the pediatric population. Growth hormone is not uniformly helpful and has only been approved for a small number of conditions.

Vosoritide is an investigational drug that directly targets the growth plate to promote growth. It is an analog of the amino acid C-type natriuretic peptide (CNP). It binds its receptor on healthy cartilage cells called chondrocytes and is currently under investigation in clinical trials as a treatment for the bone growth disorder achondroplasia.

“Vosoritide for Selected Genetic Causes of Short Stature” is a Phase 2 study currently open at Children’s National Hospital. This study will target five types of genetic short stature including SHOX deficiency, hypochondroplasia, Rasopathies (which includes Noonan syndrome), heterozygous NPR2 defects and CNP deficiency.

Thirty-five children with short stature will be enrolled and followed for a six-month observation period to obtain baseline growth velocity, safety profile and quality of life assessment. Study participants will then be treated with vosoritide for 12 months and will be assessed for safety and improvement in growth outcomes.

“Many patients who present with short stature likely have genetic defects in genes involved in growth plate physiology. Those patients with selected causes of short stature that interact with the CNP pathway may benefit from treatment with vosoritide, which directly targets the growth plate,” said Andrew Dauber, M.D., MMSc., lead investigator of this clinical study and chief of Endocrinology at Children’s National Hospital, a program ranked in the top 10 by U.S. News & World Report. “In this study, our goal is to understand if vosoritide may be a safe and effective treatment option for certain genetically defined short stature syndromes.”

This clinical trial has been approved by the FDA and funded by BioMarin. Children’s National is the only site in the world offering this therapy for patients with these conditions. The study is currently underway and subject recruitment is ongoing. There are 9 participants enrolled to date.

“This study could fundamentally change the way we treat certain growth disorders”, says Dr. Dauber.

For more information on the clinical trial, click here.