Pfizer Japan Inc. and Opko Health, Inc. announced that the next generation long-acting growth hormone injection, Ngenla (somatrogon) Inj. 24 mg Pens and 60 mg Pens, has been approved by the Ministry of Health, Labour and Welfare (MHLW) in Japan.

Ngenla is a once-weekly long-acting recombinant human growth hormone, for the indication of short statue due to growth hormone deficiency without closed epiphyses. Ngenla provides patients with paediatric growth hormone deficiency (GHD) with a new option that reduces treatment frequency from daily injections to once-weekly injections.

This approval is based on the results of a phase 3 study conducted in Japanese subjects and a global phase 3 clinical study, both of which were conducted in subjects with paediatric GHD, and both of which compared the efficacy and safety of once-weekly Ngenla with Genotropin (somatropin), a recombinant human growth hormone for injection administered once-daily. In both studies, Ngenla showed comparable efficacy to Genotropin in the primary endpoint of annual height velocity at 12 months. Ngenla was generally well tolerated in both studies, with comparable safety to that of Genotropin administered once-daily with respect to the types, numbers and severity of the adverse events observed between the treatment arms.

“We are pleased to receive approval for once-weekly Ngenla, which offers a new treatment option for paediatric GHD patients that can help reduce the burden associated with daily growth hormone administration. We wish to express our gratitude to the patients and their families who participated in the clinical studies and to all the sites conducting these trials,” said Taro Ishibashi, president of Pfizer R&D Japan G.K.

In 2014, Pfizer and Opko Health 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 somatrogon for GHD.

The phase 3 study of Ngenla in 44 treatment-naïve Japanese pre-pubertal children with paediatric GHD was a 12-month, open-label, randomized, active-controlled, parallel-group study of the efficacy and safety of weekly Ngenla compared to recombinant human growth hormone (r-hGH), Genotropin (somatropin) for injection treatment administered once-daily. Eligible patients were randomized in a 1:1 ratio to receive either once-weekly Ngenla or Genotropin administered once-daily (reference therapy, 0.025 mg/kg/day which is equivalent to 0.175 mg/kg/week). To obtain pharmacokinetic information of three different weekly doses in Japanese pediatric GHD patients, Ngenla treated patients received 0.25 mg/kg/week for 2 weeks, followed by 0.48 mg/kg/week for 2 weeks followed by 0.66 mg/kg/week for the remaining 46 weeks.

The global phase 3 study of Ngenla in 224 treatment-naïve children with paediatric GHD in over 20 countries was a 12-month randomized, open-label, active-controlled study evaluating the safety and efficacy of weekly Ngenla (somatrogon) injection compared to Genotropin (somatropin) administered once-weekly. Eligible patients 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.

Ngenla is a 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. Ngenla was approved in Canada in October 2021 and in Australia in November 2021.

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.

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. Children may also experience other problems with physical health and mental well-being.

Opko is a multinational biopharmaceutical and diagnostics company that seeks to establish industry-leading positions in large, rapidly growing markets by leveraging its discovery, development and commercialization expertise and novel and proprietary technologies.