Somapacitan

Introduction

Somapacitan is a long acting, recombinant growth hormone analog that is used to treat adults and children two years of age or older with growth hormone deficiency. Somapacitan has not been linked to elevations in serum aminotransferase levels or bilirubin levels during therapy or to instances of clinically apparent liver injury with symptoms or jaundice.

Background

Somapacitan (soe” ma pas’ i tan) is a long acting, recombinant form of human growth hormone that is used to treat both adults and children with growth hormone deficiency. Human growth hormone (GH) is a 191-amino acid polypeptide produced by the pituitary gland that has widespread effects on many organs and tissues either directly via growth hormone receptors or indirectly via production of insulin like growth factor-1 (IGF-1) by the liver. Deficiency in growth hormone is associated with short stature and abnormalities in body composition and metabolic factors. Replacement with recombinant human growth factor preparations can correct these abnormalities, increasing linear growth in children as well as increasing muscle and bone growth and decreasing fat mass. Somapacitan differs from typical recombinant human growth factor (somatotropin) in being administered weekly rather than daily by subcutaneous injection. Somapacitan is a slightly modified analog with amino acid 109 being changed to a cysteine with a long side chain with an albumin binding receptor. In the circulation, somapacitan binds to albumin which prolongs its half-life allowing for once weekly administration. In a registration randomized controlled trial in adults, somapacitan led to increases in serum IGF-1 levels, increases in lean body mass, and reduction in total body fat percentage, thus correcting abnormalities in body composition associated with growth hormone deficiency. In pediatric trials, somapacitan led to improvements in growth and physical development compatible with correction of growth hormone deficiency. For both children and adults, changes in body composition with somapacitan therapy were similar to those achieved with FDA approved recombinant growth hormone products that required daily administration. Somapacitan was approved in the United States in 2020 for treatment of adults with growth hormone deficiency. In 2023, the indications were extended to children 2.5 years of age or older with growth failure due to inadequate endogenous growth hormone secretion. Somapacitan is available in solution in self-injection pens of 5, 10, or 15 mg in 1.5 mL of normal saline under the brand name Sogroya. Somapacitan is administered subcutaneously once weekly. The recommended dose is based upon age and body weight and is titrated up from an initial low dose based upon clinical response, IGF-1 levels, and patient tolerance. Somapacitan therapy should be prescribed and supervised by a physician who is experienced in the diagnosis and management of growth hormone deficiency. Common side effects include back pain, arthralgia, dyspepsia, sleep disorder, dizziness, peripheral edema, nausea and vomiting, systemic arterial hypertension, weight gain, and anemia. Rare potentially severe adverse effects may include increased risk of malignancy, glucose intolerance and diabetes, intracranial hypertension, hypersensitivity reactions, marked fluid retention, hypoadrenalism, hypothyroidism, pancreatitis, and lipohypertrophy or lipoatrophy at the sites of administration.

Somapacitan is a long acting recombinant human growth hormone analog. Other FDA approved therapies of growth hormone deficiency include recombinant growth hormone products (somatotropins) that are administered daily. Switching daily therapy to weekly injections of somapacitan can be done but requires careful titration and individualization of the weekly doses.

Hepatotoxicity

In preregistration trials, discussion of adverse events rarely mentioned serum aminotransferase elevations and did not report instances of clinically apparent liver injury. Somapacitan has been usually described as well tolerated with only mild or moderate adverse events, the majority of which were considered unrelated to treatment and occurred at similar rates in placebo recipients or subjects treated with recombinant growth hormone products requiring daily injections. Since its licensure and more widescale clinical use, there have been no published reports of acute liver injury attributed to somapacitan.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Liver test abnormalities are rare during somapacitan therapy and are generally considered unrelated to the recombinant protein. The lack of liver injury during somapacitan therapy is probably because it is metabolized by tissue proteases to short polypeptides or amino acids and does not interact with hepatic cytochrome P450 enzymes.

Outcome and Management

The product label for somapacitan does not recommend monitoring of routine liver tests during therapy. A rise in serum aminotransferase levels or bilirubin during therapy should trigger evaluation for other possible causes.

Drug Class: Growth Hormone Deficiency Agents