Brief Therapeutic Update from PES Drugs and Therapeutics Committee
Sogroya® (somapactian)
Once weekly Sogroya® (somapacitan-beco, Novo Nordisk) was approved by the United States Food and Drug Administration (FDA) for treatment in pediatric growth hormone deficiency (GHD), for children 2.5 years and older, in April 2023. It was previously approved by the FDA for adult GHD in August 2020. It is currently under review for approval by Health Canada.
Long-acting growth hormone (LAGH) formulations are now readily available and have been shown to provide similar growth effects and safety to traditionally used daily growth hormone (DGH) when used in pediatric GHD [1]. They provide an alternative to DGH for patients and families with perhaps potential improvement in adherence. Other formulations of LAGH, such as NGENLA™ (somatrogon, Pfizer), Skytrofa® (lonapegsomatropin, Ascendis Pharma) and now Sogroya®, are approved and available for pediatric GHD depending on jurisdiction and approval authority. There are also other LAGH formulations available in Asia. The different LAGH formulations vary in their mechanisms that lead to their long-acting pharmacokinetics. Sogroya’s long-acting pharmacokinetics is due to the addition of an albumin binding moiety to the human growth hormone (hGH) analog that binds to endogenous albumin. The reversible binding to endogenous albumin delays elimination of somapacitan and thereby prolongs the in vivo half‑life and duration of action. Importantly, as opposed to consistent dosing between DGH formulations, the suggested dosing of the different LAGH formulations differ between each other.
Phase 2 and 3 studies [2,3] showed similar growth velocity with weekly Sogroya compared to DGH treatment. The youngest patients studied were 2.5 years old. The REAL4 phase 3 study included a 52-week main phase. Participants were randomized 2:1 to weekly Sogroya (0.16 mg/kg/week, n=132) or daily somatropin (0.034 mg/kg/day, 0.24 mg/kg/week, n=68). Growth velocity was noninferior at 11.2 cm/y with weekly Sogroya and 11.7 cm/y with daily somatropin. There is currently a 3-year extension study during which all participants receive Sogroya.
Frequency of adverse events were similar between the study groups. Adverse events with Sogroya included nasopharyngitis, headache, pyrexia, pain in extremity, and injection site reactions. Generally, there is a concern of increased injection site reactions with LAGH compared to DGH, however, in the Sogroya study, injection site reactions were similar and present in 6.1% of Sogroya participants compared 5.9% of somatropin participants. Like with DGH, other potential adverse events could include sudden death in patients with Prader Willi Syndrome, second neoplasms in cancer survivors, slipped capital femoral epiphyses, scoliosis, pancreatitis, hyperglycemia, intracranial hypertension, and fluid retention [3,4].
The Sogroya Flex Pro device is available in three prefilled formulations of 5 mg (0.025 mg dosing increments, 0.025 to 2 mg dose delivery range), 10 mg (0.05 mg dosing increments, 0.05 to 4 mg dose delivery range) and 15 mg (0.1 mg dosing increments, 0.1 to 8 mg dose delivery range). It does not require reconstitution and is stable at room temperature for 72 hours. Suggested dosing is 0.16 mg/kg/week subcutaneously, for both treatment-naïve patients and those switching from daily GH [4].
With all LAGH preparations, it is suggested to monitor insulin like growth factor-1 (IGF-1) levels. For Sogroya, it is suggested to do so on day 3 to 4 after the injection. While further study is needed and specific guidance is not well-defined, it is suggested to decrease the dose if IGF-1 concentrations are above the age and gender specific normal range [4].
References:
- Miller BS. What do we do now that the long-acting growth hormone is here? Front Endocrinol (Lausanne). 2022 Aug 22;13:980979. doi: 10.3389/fendo.2022.980979. PMID: 36072938; PMCID: PMC9441929.
- Sävendahl L, Battelino T, Brod M, Højby Rasmussen M, Horikawa R, Juul RV, Saenger P; REAL 3 study group. Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1847–61. doi: 10.1210/clinem/dgz310. Erratum in: J Clin Endocrinol Metab. 2020 Dec 1;105(12): PMID: 31917835; PMCID: PMC7069655.
- Miller BS, Blair JC, Rasmussen MH, et al. Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial. J Clin Endocrinol Metab. 2022;107(12):3378-3388. doi:10.1210/clinem/dgac513. PMID: 36062966; PMCID: PMC9693810.
- SOGROYA® (somapacitan-beco) injection, for subcutaneous use [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2023.
Prepared on behalf of PES Drugs and Therapeutics Committee by Drs. Seth D. Marks, Emily Breidbart, Ryan Miller, and Anna Ryabets-Lienhard.