Pfizer and OPKO's Once-Weekly Long-Acting Somatrogon Accepted for FDA Review as a Novel Treatment for Pediatric Growth Hormone Deficiency

January 07, 2021 /BioValleyBIOON/ --Pfizer(Pfizer) and OPKO Health, Inc. recently announced jointly that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for somatrogon, a long-acting human growth hormone (hGH) administered once weekly for the treatment of pediatric patients with growth hormone deficiency (GHD).FDAThe Prescription Drug User Fee Act (PDUFA) target date has been set for October 2021.

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 experience 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 human chorionic gonadotropin (hCG) beta-subunit C-terminal peptide (CTP) 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 implementing the clinical program, while Pfizer was responsible for product registration and commercialization. The two parties would evaluate the potential for other pediatric and adult indications as appropriate.

Dr. Brenda Cooperstone, Chief Development Officer for Rare Diseases at Pfizer Global Product Development, stated: “FDA“The acceptance of our application is an exciting step, and our goal is to provide a long-acting, once-weekly treatment option for children with GHD. If approved, somatrogon will help reduce the burden of daily growth hormone injections on children and their families and caregivers. For 35 years, Pfizer has been committed to improving outcomes for patients with GHD, and somatrogon is another example of how we strive to positively impact quality of life and treatment adherence, helping to ensure that these patients can reach their full potential.”

This application is based on a Phase 3Clinical Trialsupported by the results. This was a randomized, open-label, active-controlled trial conducted in more than 20 countries, enrolling and treating 224 children with growth hormone deficiency (GHD) who had not previously received treatment. In the study, patients were randomized in a 1:1 ratio to two treatment groups: somatrogon (0.66 mg/kg once weekly) or Genotropin (somatropin; 0.034 mg/kg once daily). The primary endpoint was height velocity after 12 months of treatment. Secondary endpoints included changes in height standard deviation score 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 they could continue or switch to somatrogon treatment. Approximately 95% of patients transitioned into the open-label extension study and received somatrogon.

The results demonstrated 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) between somatrogon and Genotropin was 0.33 (two-sided 95% confidence interval: -0.39, 1.05). Compared with the Genotropin group, the somatrogon group showed greater changes in height standard deviation score (a key secondary endpoint) at both 6 and 12 months. Furthermore, at 6 months, the somatrogon group exhibited 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: USFDA ACCEPTS REGULATORY SUBMISSION FROM PFIZER AND OPKO FOR REVIEW OF SOMATROGON TO TREAT PEDIATRIC PATIENTS WITH GROWTH HORMONE DEFICIENCY