"This submission for VOXZOGO is supported by the largest body of evidence for any medicine in achondroplasia, reflecting BioMarin's long-standing commitment to advancing the science of skeletal growth. The clinical data demonstrate meaningful improvements across multiple skeletal growth-related measures beyond annualized growth velocity in children with this condition," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "If approved, VOXZOGO would be the first therapy for achondroplasia to convert from accelerated approval to traditional approval based on a comprehensive clinical data package, including adult height outcomes and other clinical measures evaluated over extended follow-up."
The sNDA submission was supported by substantial long-term safety and efficacy data from three ongoing studies (111-205, 111-208 and 111-302), including clinically meaningful results in growth and improvements across key skeletal growth-related measures, including proportionality and arm span. The full package submitted to the FDA included the longest efficacy and safety data of any medicine studied in achondroplasia.
VOXZOGO received FDA accelerated approval in 2021, a pathway enabling faster patient access based on measures reasonably likely to predict clinical benefit. This sNDA is intended to fulfill the postmarketing requirement to confirm that benefit and convert to full approval, supported by long-term data from three ongoing studies demonstrating clinically meaningful improvements in growth and skeletal health outcomes in children with achondroplasia.
About Achondroplasia
Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull. This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth.
More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still "open," typically those under 18 years of age. Approximately 25% of people with achondroplasia fall into this category.
About VOXZOGO (vosoritide)
In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.
VOXZOGO is the only approved medicine to support the growth of children with achondroplasia starting from birth, with international consensus guidelines recommending initiation of VOXZOGO as early as possible. First approved in 2021, VOXZOGO has helped more than 5,000 infants and children in more than 50 countries. Through our ongoing studies, BioMarin continues to evaluate VOXZOGO on key clinical endpoints relevant for achondroplasia patients, such as arm span, tibial bowing (leg bowing), body proportionality, spinal morphology (including spinal stenosis) and quality of life measures.
VOXZOGO is approved in the U.S., Japan and Australia to increase linear growth in children of all ages with achondroplasia with open epiphyses, and VOXZOGO is indicated in the EU for the treatment of achondroplasia in children 4 months of age and older whose epiphyses are not closed, as confirmed by appropriate genetic testing. In the U.S., this indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history.
Patient Support Accessing VOXZOGO
BioMarin's robust support services have ensured a seamless treatment experience, spearheaded by Clinical Coordinators, who have conducted hundreds of trainings for families with achondroplasia since approval. BioMarin provides resources to support families navigating achondroplasia, including a caregiver mentorship program that connects parents with other caregivers, and a U.S. doctor directory that helps families and healthcare professionals identify clinicians experienced in achondroplasia care.
What is VOXZOGO used for?
VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses).
VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
What is the most important safety information about VOXZOGO?
VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO.
What are the most common side effects of VOXZOGO?
The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away.
How is VOXZOGO taken?
- VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made.
- Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual.
- The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups.
- Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider.
What should you tell the doctor before or during taking VOXZOGO?
Tell your doctor about all of the patient's medical conditions including
If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine).
If the patient has kidney problems or renal impairment.
If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby.
If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk.
Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
About BioMarin
BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with nine commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients.
For more information please visit, www.biomarin.com.
