Pediatric Growth Hormone Deficiency: Drugs in the Pipeline

Christina Loguidice

Growth hormone deficiency (GHD) results when the pituitary gland does not produce enough growth hormone, resulting in short stature, delayed or absent puberty, and changes in muscle mass, cholesterol levels, and bone strength. The condition can be congenital, resulting from genetic mutations or structural malformations in the brain, or acquired, resulting from trauma, infections, tumors, radiation therapy, or other causes. Because congenital GHD comprises a wide spectrum of etiological disorders, including combined pituitary hormone deficiency, it has a wide incidence range, occurring in 1 in 3500 to 4 in 100,000 live births.1
Currently, the standard of care is subcutaneous injection of a biosynthetic recombinant human growth hormone (rhGH). The frequency of the injections is based on the patient’s level of GHD (ie, whether growth hormone is completely absent or some growth hormone is present), but most patients require daily administration. The rhGH treatments are typically given until the child’s maximum growth potential is achieved, often necessitating many years of treatment, increasing the risk of poor compliance. Two promising agents are under investigation that may alleviate the burden of treatment by reducing the frequency of injections: VRS-317 and hGH-CTP. The companies developing these agents have both made recent announcements regarding the advancement of these agents.


On January 8, 2015, Versartis, Inc., announced initiation of a global phase 3 study of VRS-317, a long-acting form of rhGH that enables semi-monthly dosing in children with GHD.2 This registration trial, dubbed VELOCITY (Versartis Long-Acting Growth Hormone in Children Compared to Daily rhGH), follows positive data from Versartis’ completed phase 1b/2a VERTICAL (Versartis Trial in Children to Assess Long-Acting Growth Hormone) study and the ongoing long-term extension study.
VELOCITY, which is being conducted in the United States, Canada, and Western Europe, is expected to enroll approximately 136 treatment-naïve, prepubescent children with GHD. Patients will be randomly assigned in a 3:1 ratio to 3.5 mg/kg semi-monthly VRS-317 or to 34 µg/kg daily rhGH with somatropin (rDNA origin). The primary endpoint is noninferiority between the 2 treatment groups for 12-month height velocity. Upon completion of the study, all patients will be offered the opportunity to continue treatment with VRS-317 in the ongoing pediatric extension study. Versartis expects 6-month interim results in mid-2016 and final data in early 2017.
“After 12 months of continuous dosing with VRS-317 in our phase 1b/2a and extension study, we are confident in our trial design and look forward to furthering the development of our lead product candidate as a semi-monthly treatment. Our team has extensive knowledge and experience in bringing growth hormone therapies to market and we are diligently working towards commercializing VRS-317 for patients and families who suffer with the burden of daily dosing events,” said Jeffrey L. Cleland, PhD, chief executive officer of Versartis in a company press release.
Enrollment information for the VELOCITY trial can be found here.


On December 15, 2014, OPKO Health, Inc., announced that it has partnered with Pfizer to develop and commercialize human growth hormone modified by carboxyl terminal peptide (hGH-CTP) for the treatment of GHD in adults and children, as well as for the treatment of growth failure in children born small for gestational age who do not show catch-up growth by 2 years of age.3 As part of this agreement, OPKO will receive an upfront payment of $295 million from Pfizer and will be eligible to receive up to an additional $275 million upon achievement of regulatory milestones. In turn, upon Pfizer’s commercialization of hGH-CTP, OPKO is eligible to receive royalty and/or profit sharing payments. Pfizer will obtain exclusive license to commercialize hGH-CTP globally.
OPKO’s hGH-CTP is a novel, long-acting rhGH analog that is administered once weekly. This agent features the company’s proprietary carboxyl terminal peptide technology (CTP), which enables the hormone’s half-life to be extended without the need for polymers, encapsulation techniques, or nanoparticles. In 2010, the FDA granted orphan drug designation to hGH-CTP as a treatment for adults and children with GHD. The agent also has orphan drug designation in Europe. OPKO is currently undertaking a phase 2 clinical trial in pediatric patients and has an ongoing pivotal phase 3 clinical trial in adults.


1.  BMJ Best Practice. Growth hormone deficiency in children. Last updated July 25, 2014. Accessed February 3, 2015.
2.  Versartis initiates global phase 3 study of VRS-317 in children with growth hormone deficiency [news release]. Menlo Park, CA: Versartis; January 8, 2015. Accessed February 3, 2015.
3. OPKO and Pfizer Enter into Global Agreement for OPKO’s Long-Acting Human Growth Hormone (hGH-CTP) [news release]. Jersey City, NJ: Pfizer; December 15, 2014. Accessed February 3, 2015.
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