OPKO Health recently announced that its partner Pfizer Japan has submitted a new drug application (NDA) for somatrogon to the Ministry of Health, Labour and Welfare (MHLW) of Japan, which is a long-acting human growth hormone (hGH), weekly Medication once for the treatment of children with growth hormone deficiency (GHD). Earlier this month, Pfizer and OPKO announced that the U.S. FDA has accepted somatrogon’s Biological Products Licensing Application (BLA) and has designated the Prescription Drug User Fee Act (PDUFA) as a target date of October 2021. If approved, somatrogon will bring a long-lasting, weekly treatment option, which will help reduce the burden of daily growth hormone injections for children with GHD, their relatives and caregivers.
The Japanese application is based on the results of a Phase 3 study in Japan and a Phase 3 study worldwide. These studies were carried out in children with GHD and compared the efficacy and safety of somatrogon (administered once a week) and recombinant human growth hormone Genotropin (somatropin, administered once a day) for injection. In both studies, after 12 months of treatment, somatrogon was as effective as Genotropin in terms of the primary endpoint of annual height velocity. In the two studies, somatrogon was generally well tolerated and had safety comparable to Genotropin. The types, numbers, and severity of adverse events observed between the two treatment groups were similar.
Childhood GHD is a serious and rare disease caused by insufficient growth hormone secreted by the pituitary gland. Children with GHD are not only short in stature, but also have metabolic abnormalities, psychosocial challenges, cognitive deficits, and poor quality of life. For decades, the standard of care for GHD has been a subcutaneous injection of human growth hormone (hGH) once a day to improve growth and metabolic effects. For caregivers and patients, the treatment burden of daily injections is high, which may lead to poor compliance and reduce the overall treatment effect.
Somatrogon is a new molecular entity that contains the natural sequence of human growth hormone, and contains one copy at the N-terminus and 2 copies at the C-terminus of human chorionic gonadotropin (hCG) β-chain C-terminal peptide (CTP), CTP Can extend the half-life of the molecule. In the United States and the European Union, somatrogon has been granted Orphan Drug Designation (ODD) for the treatment of children and adults with GHD. The results of the research to date show that compared with hGH once a day, somatrogon once a week can significantly reduce lifestyle disturbances, support patient preferences, and improve compliance.
In 2014, Pfizer and OPKO signed a global agreement to develop and commercialize somatrogon for the treatment of GHD. According to the agreement, OPKO is responsible for the implementation of clinical projects, and Pfizer is responsible for product registration and commercialization. Both parties will evaluate the possibility of other indications for children and adults as appropriate.
In the United States, somatrogon's BLA is supported based on the results of global phase 3 clinical trials. This is a randomized, open-label, positive drug controlled trial conducted in more than 20 countries, enrolling and treating 224 children with GHD who have not previously received treatment. In the study, these patients were randomly assigned to two treatment groups at a ratio of 1:1: somatrogon treatment group (0.66 mg/kg, once a week), Genotropin (somatropin) treatment group (0.034 mg/kg, daily administration once). The primary end point of the trial is the height velocity during 12 months of treatment. Secondary endpoints include changes in height standard deviation at 6 months and 12 months, safety, and pharmacodynamic indicators. Children who complete the study have the opportunity to participate in a global, open-label, multicenter, long-term extension study, in which patients can continue to receive or switch to somatrogon treatment. Approximately 95% of patients have been transferred to the open label extension study and have received somatrogon treatment.
The results showed that the study reached the primary endpoint of non-inferiority: the least squares mean (10.12 cm/year) of the somatrogon group was higher than that of the Genotropin group (9.78 cm/year); height growth rate (cm/year) The treatment difference (somatrogon-Genotropin) was 0.33 (two-sided 95% confidence interval: -0.39, 1.05). Compared with the Genotropin group, the somatrogon group had higher changes in height standard deviation scores (key secondary endpoints) at 6 and 12 months. In addition, at 6 months, compared with the Genotropin group, the somatrogon group had a higher change in height growth rate, another key secondary endpoint. In a clinical setting, these commonly used growth measurement methods are used to measure the potential that subjects may experience to catch up with age- and gender-matched peers' height growth.
In this study, somatrogon was generally well tolerated, and the type, number and severity of adverse events observed between treatment groups were comparable to the once-daily growth hormone Genotropin.