Pfizer Inc and OPKO Health Inc, a multinational biopharmaceutical and diagnostics company, announced that the US Food and Drug Administration (FDA) has accepted for filing the initial Biologics License Application (BLA) for somatrogon, a long-acting human growth hormone that is intended to be administered once-weekly for the treatment of pediatric patients with growth hormone deficiency (GHD).
The target Prescription Drug User Fee Act (PDUFA) action date for decision by the US FDA is in October 2021. Somatrogon is an investigational new biologic product that is glycosylated and comprises the amino acid sequence of human growth hormone and one copy of the C-terminal peptide (CTP) from the beta chain of human chorionic gonadotropin (hCG) at the N-terminus and two copies of CTP (in tandem) at the C-terminus. The glycosylation and CTP domains account for the half-life of the molecule.
“The US FDA’s filing acceptance is an encouraging step closer to our goal of providing a long-acting, once-weekly therapy for pediatric patients living with GHD. If approved, somatrogon could help reduce the burden of daily growth hormone injections on children, their loved ones, and caregivers,” said Brenda Cooperstone, MD, chief development officer, Rare Disease, Pfizer Global Product Development. “For 35 years, Pfizer has been committed to improving the outcomes of patients living with GHD, and somatrogon is another example of how we are working to positively impact quality of life and treatment compliance to help ensure those patients can reach their full potential.”
The submission is supported by the results of a global phase 3 trial evaluating the safety and efficacy of somatrogon administered once weekly to pediatric patients with GHD. This study met its primary endpoint of non-inferiority compared to Genotropin (somatropin) for injection administered once daily, as measured by annual height velocity at 12 months.
The top-line results from the study demonstrated the least square mean was higher in the somatrogon group (10.12 cm/year) than in the somatropin group (9.78 cm/year); the treatment difference (somatrogon – somatropin) in height velocity (cm/year) was 0.33 with a two-sided 95% confidence interval of the difference (-0.39, 1.05). In addition, change in height standard deviation scores at 6 and 12 months, key secondary endpoints, were higher in the somatrogon dosed once-weekly cohort in comparison to the somatropin dosed once-daily cohort.
Moreover, at 6 months, change in height velocity, another key secondary endpoint, was higher in the somatrogon dosed once-weekly cohort in comparison to the somatropin dosed once-daily cohort. These common measures of growth are employed in the clinical setting to measure the potential level of catch-up growth that subjects may experience relative to the heights of their age and gender matched peers.
In 2014, Pfizer and OPKO entered into a worldwide agreement for the development and commercialization of somatrogon for the treatment of GHD. Under the agreement, OPKO is responsible for conducting the clinical program and Pfizer is responsible for registering and commercializing the product.
The somatrogon phase 3 trial is a randomized, open-label, active-controlled study conducted in over 20 countries. This study enrolled and treated 224 pediatric patients, treatment-naïve children with growth hormone deficiency who were randomized 1:1 into two arms: somatrogon administered at a dose of 0.66 mg/kg body weight once-weekly vs Genotropin (somatropin) administered at a dose of 0.034 mg/kg body weight once daily.
The primary endpoint of the trial was height velocity at 12 months. Secondary endpoints included change in height standard deviation at 6 and 12 months, safety and pharmacodynamic measures. Children completing this study had the opportunity to enroll in a global, open-label, multicenter, long-term extension study, in which they were able to either continue receiving or switch to somatrogon. Approximately 95% of the patients switched into the open-label extension study and received somatrogon treatment.
Somatrogon is an investigational biologic product that is glycosylated and comprises the amino acid sequence of human growth hormone and one copy of the C-terminal peptide (CTP) from the beta chain of human chorionic gonadotropin (hCG) at the N-terminus and two copies of CTP (in tandem) at the C-terminus. The glycosylation and CTP domains account for the half-life of the molecule. Somatrogon has received Orphan Drug designation in the US and the EU for the treatment of children and adults with growth hormone deficiency.
Growth hormone deficiency is a rare disease characterized by the inadequate secretion of growth hormone from the pituitary gland and affects one in approximately 4,000 to 10,000 people. In children, this disease can be caused by genetic mutations or acquired after birth. Because the patient's pituitary gland secretes inadequate levels of somatropin, the hormone that causes growth, his or her height may be affected and puberty may be delayed. Without treatment, he or she will have persistent growth attenuation, a very short height in adulthood, and may experience other health problems.
Genotropin (Somatropin) is a man-made, prescription treatment option, approved in the United States for children who do not make enough growth hormone on their own, have the genetic condition called Prader-Willi syndrome (PWS), were born smaller than most other babies, have the genetic condition called Turner syndrome (TS) or have idiopathic short stature (ISS). Genotropin is also approved to treat adults with growth hormone deficiency. Genotropin is taken by injection just below the skin and is available in a wide range of devices to fit a range of individual dosing needs. Genotropin is just like the natural growth hormone that our bodies make and has an established safety profile.