Pfizer Submits New Drug Application in Japan for Once-Weekly Somatrogon to Treat Pediatric Growth Hormone Deficiency

January 29, 2021/BioonBIOON/--OPKO Health, Inc. recently announced that its partnerPfizer(Pfizer) Japan has submitted a New Drug Application (NDA) for somatrogon to the Japanese Ministry of Health, Labour and Welfare (MHLW). Somatrogon is a long-acting human growth hormone (hGH) administered once weekly for the treatment of pediatric patients with growth hormone deficiency (GHD). Earlier this month, Pfizer and OPKO announced that the United StatesFDAThe Biologics License Application (BLA) for somatrogon has been accepted, and the Prescription Drug User Fee Act (PDUFA) target date has been set for October 2021. If approved,Somatrogon will provide a long-acting, once-weekly treatment option, which will help alleviate the burden of daily growth hormone injections for children with GHD and their families and caregivers.

This application in Japan is based on the results of one Phase 3 study conducted in Japan and one global Phase 3 study. These studies were conducted in pediatric patients with growth hormone deficiency (GHD) and compared the efficacy and safety of somatrogon (administered once weekly) with Genotropin (somatropin for injection, administered once daily). In these two studies,After 12 months of treatment, somatrogon demonstrated comparable efficacy to Genotropin in terms of the primary endpoint, annual height velocity.In two studies, somatrogon was generally well tolerated, with a safety profile comparable to that of Genotropin; the types, frequency, and severity of adverse events observed were similar between the two treatment groups.

Pediatric growth hormone deficiency (GHD) is a serious rare disease caused by insufficient secretion of growth hormone from the pituitary gland. Children with GHD not only exhibit short stature but also face metabolic abnormalities, psychosocial challenges, cognitive deficits, and poor quality of life. For decades, the standard of care for GHD has been once-daily subcutaneous injections of human growth hormone (hGH) to improve growth and metabolic outcomes. The high treatment burden of daily injections for caregivers and patients may lead to poor adherence, thereby reducing overall treatment efficacy.

Somatrogon is a new molecular entity that contains the natural sequence of human growth hormone, with one copy of the C-terminal peptide (CTP) of the human chorionic gonadotropin (hCG) β-subunit at the N-terminus and two copies at the C-terminus; the CTP extends the half-life of the molecule. In both the United States and the European Union, somatrogon has been granted orphan drug designation (ODD) for the treatment of children and adults with growth hormone deficiency (GHD). Research to date indicates that, compared with once-daily hGH, once-weekly somatrogon significantly reduces lifestyle disruption, aligns with patient preferences, and improves adherence.

In 2014, Pfizer and OPKO entered into a global agreement to develop and commercialize somatrogon for the treatment of GHD. Under the agreement, OPKO was responsible for executing the clinical program, while Pfizer was responsible for product registration and commercialization. Both parties would evaluate the potential for additional pediatric and adult indications as appropriate.

In the United States, the BLA for somatrogon, based on global Phase 3Clinical Trialssupported by the results. This was a randomized, open-label, active-controlled trial conducted in more than 20 countries, which enrolled and treated 224 pediatric patients with growth hormone deficiency (GHD) who had not previously received treatment. In the study, these patients were randomly assigned in a 1:1 ratio to two treatment groups: the somatrogon group (0.66 mg/kg, administered once weekly) and the Genotropin (somatropin) group (0.034 mg/kg, administered once daily). The primary endpoint of the trial was height velocity after 12 months of treatment. Secondary endpoints included changes in height standard deviation scores at 6 and 12 months, safety, and pharmacodynamic markers. Children who completed the study had the opportunity to participate in a global, open-label, multicenter, long-term extension study, in which patients could continue or switch to somatrogon treatment. Approximately 95% of patients transitioned into the open-label extension study and received somatrogon treatment.

The results showed that the study met its primary non-inferiority endpoint: at 12 months of treatment, the least squares mean for the somatrogon group (10.12 cm/year) was higher than that for the Genotropin group (9.78 cm/year); the treatment difference in height velocity (cm/year) (somatrogon minus Genotropin) was 0.33 (two-sided 95% confidence interval: -0.39, 1.05). Compared with the Genotropin group, the somatrogon group demonstrated greater changes in height standard deviation score (a key secondary endpoint) at both 6 and 12 months. Furthermore, at 6 months, the somatrogon group showed a greater change in another key secondary endpoint, height velocity, compared with the Genotropin group. In clinical practice, these commonly used growth metrics are employed to assess the potential for catch-up growth in subjects relative to age- and sex-matched peers.

In this study, somatrogon was generally well tolerated, with the types, frequency, and severity of adverse events observed across treatment groups being comparable to those of once-daily Genotropin (growth hormone). (Bioon.com)

Original Source: New Drugapplication Submitted to PMDA in Japan for Somatrogon, to Treat Pediatric Patients with Growth Hormone Deficiency