Sogroya

Important Dosing and Administration Information

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SOGROYA treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients with growth failure due to GHD and/or adults with GHD [see Indications and Usage ].

Recommended Dosage and Monitoring for Pediatric Patients with GHD

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Recommended dosage of SOGROYA is 0.16 mg/kg based on actual body weight once weekly for treatment-naïve patients and patients switching from daily growth hormone (somatropin).

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Individualize dosage for each patient based on the growth response.

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When switching from daily human growth hormone to once-weekly SOGROYA, choose the preferred day for the weekly dose. Take the final dose of daily treatment on the day before (or at least 8 hours before) the first dose of SOGROYA.

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When switching from a weekly human growth hormone to once-weekly SOGROYA, continue once weekly dosing schedule.

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Assess compliance and evaluate other causes of poor growth such as hypothyroidism, undernutrition, advanced bone age, and antibodies to recombinant human growth hormone if patients experience failure to increase height velocity, particularly during the first year of treatment.

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Patients who were treated with SOGROYA for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuing SOGROYA.

Recommended Dosage, Titration, and Monitoring for Adult Patients with GHD

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Initiate SOGROYA with a dosage of 1.5 mg once weekly for treatment naïve patients and patients switching from daily growth hormone (somatropin).

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Increase the weekly dosage every 2 to 4 weeks by approximately 0.5 mg to 1.5 mg until the desired response is achieved.

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Titrate the dosage based on clinical response and serum insulin-like growth factor-1 (IGF-1) concentrations. Draw IGF-1 samples 3 to 4 days after the prior dose.

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Decrease the dosage as necessary on the basis of adverse reactions and/or serum IGF-1 concentrations above the age- and sex-specific normal range.

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The maximum recommended dosage is 8 mg once weekly.

Recommended Dosage and Titration for Specific Populations

Patients Aged 65 Years and Older

Initiate SOGROYA with a dosage of 1 mg once weekly and use smaller dose increment increases when titrating the dosage [see Use in Specific Populations ]. See above for monitoring recommendations and the maximum recommended dosage of SOGROYA [see Dosage and Administration ].

Patients with Hepatic Impairment

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SOGROYA is not recommended in adult and pediatric patients with severe hepatic impairment [see Hepatic Impairment ].

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For adult patients with moderate hepatic impairment, initiate SOGROYA with a dosage of 1 mg once weekly and use smaller dose increment increases when titrating the dosage. See above for monitoring recommendations [see Dosage and Administration and Pharmacokinetics ]. The maximum recommended dosage is 4 mg once weekly.

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For pediatric patients with moderate hepatic impairment, SOGROYA is not recommended [see Hepatic Impairment ].

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No dosage adjustment is recommended for adult and pediatric patients with mild hepatic impairment.

Women Receiving Oral Estrogen

Initiate SOGROYA with a dosage of 2 mg once weekly [see Drug Interactions ]. See above for titration and monitoring recommendations and the maximum recommended dosage of SOGROYA [see Dosage and Administration ].

Missed Doses

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If the dose is missed, SOGROYA can be taken within 3 days after the scheduled dosing day. Once-weekly dosing for the next dose could be resumed at the regularly scheduled dosing day.

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If more than 3 days have passed since the missed dose, skip the dose and administer the next dose on the regularly scheduled dosing day.

Pregnancy

Risk Summary

There are no available data on the use of SOGROYA during pregnancy; however, published studies describing the use of short-acting recombinant growth hormone (rhGH) during pregnancy over several decades have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneously administered somapacitan-beco was not teratogenic in rats or rabbits during organogenesis at doses approximately 12 times the clinical exposure at the maximum recommended human dose (MRHD) of 8 mg/week. No adverse developmental outcomes were observed in a pre- and post-natal development study with administration of somapacitan-beco to pregnant rats from organogenesis through lactation at approximately 275 times the clinical exposure at the MRHD (see Data).

The background risk of birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

In an embryo-fetal development study in rats, somapacitan-beco was administered by subcutaneous injection at doses of 2, 6, and 18 mg/kg/day during the period of organogenesis from gestation day 6 to 17. Fetal viability and development were not affected at doses up to 6 mg/kg/day (31 times the MRHD, based on AUC). Transient, fetal skeletal variations (short/bent/thickened long bones) were observed at 18 mg/kg/day (261 times the MRHD, based on AUC).

In an embryo-fetal development study in rabbits, somapacitan-beco was administered by subcutaneous injection at doses of 1, 3, and 9 mg/kg every two days during the period of organogenesis from gestation day 6 to 18. Fetal viability and development were not adversely affected at somapacitan-beco dose of 1 mg/kg/every two days (12 times the MRHD, based on AUC). Reduced fetal growth was observed at doses ≥3 mg/kg/every two days (≥130 times the MRHD, based on C12h).

In a pre- and post-natal development study in pregnant rats, somapacitan-beco was administered by subcutaneous injection at doses of 4, 9, and 18 mg/kg twice a week from gestation day 6 through lactation day 18. No adverse developmental effects were observed in the offspring at doses up to 9 mg/kg (275 times the MRHD, based on AUC). Increased incidence of renal pelvic dilatation was observed on post-natal day 21 at 18 mg/kg (630 times the MRHD, based on AUC), but was not observed in the adult F1 generation.

Lactation

Risk Summary

There is no information on the presence of somapacitan-beco in human milk, the effects on the breastfed infant, or the effects on milk production. Somapacitan-beco-related material was secreted into milk of lactating rats. When a substance is present in animal milk, it is likely that the substance will be present in human milk. Available published data describing administration of short-acting recombinant growth hormone (rhGH) to lactating women for 7 days reported that short-acting rhGH did not increase the normal breastmilk concentration of growth hormone and no adverse effects were reported in breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SOGROYA and any potential adverse effects on the breastfed infant from SOGROYA or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of SOGROYA have been established for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (GH) in pediatric patients 2.5 years of age and older. The use of SOGROYA for this indication is supported by evidence from a 52 week randomized, multi-center, open-label, active-controlled, parallel-group phase 3 trial in 200 treatment-naïve, pediatric patients with GHD. The safety profile from the pediatric trial was similar to that reported in adults [see Adverse Reactions and Clinical Studies ].

Risks in pediatric patients associated with growth hormone use include:

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Sudden death in pediatric patients with Prader-Willi Syndrome. SOGROYA is not indicated for the treatment of pediatric patients with growth failure secondary to genetically confirmed Prader-Willi syndrome.[see Warnings and Precautions ]

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Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head [see Warnings and Precautions ]

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Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions ]

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Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions ]

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Pancreatitis [see Warnings and Precautions ]

The safety and effectiveness of SOGROYA for the treatment of growth failure due to inadequate secretion of endogenous growth hormone have not been established in pediatric patients less than 2.5 years of age.

Geriatric Use

In clinical studies a total of 52 (15.6%) of the 333 SOGROYA-treated patients were 65 years or older and 3 (0.9%) were 75 years or older [see Clinical Studies ]. Subjects older than 65 years appeared to have higher exposure than younger subjects at the same dose level. Elderly patients may be more sensitive to the action of somapacitan-beco, and therefore may be at increased risk for adverse reactions. Initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose [see Dosage and Administration ].

Hepatic Impairment

Adult patients: No dose adjustment of SOGROYA is required for patients with mild hepatic impairment. Higher somapacitan-beco exposure was observed in patients with moderate hepatic impairment. In patients with moderate hepatic impairment, initiate SOGROYA with a dose of 1 mg once weekly and use smaller increments when increasing the dose. The maximum dose should not exceed 4 mg once weekly. Somapacitan-beco was not studied in patients with severe hepatic impairment. Therefore, use of SOGROYA is not recommended in patients with severe hepatic impairment. [see Dosage and Administration and Clinical Pharmacology ].

Pediatric patients: Based on the hepatic impairment study in adults, no dose adjustment of SOGROYA is recommended for patients with mild hepatic impairment. Higher systemic exposure of SOGROYA is expected in pediatric patients with moderate and severe hepatic impairment; therefore, SOGROYA is not recommended in these pediatric patients [see Dosage and Administration ].

Increased Mortality in Patients with Acute Critical Illness

Increased mortality has been reported after treatment with somatropin in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery and multiple accidental trauma, as well as patients with acute respiratory failure [see Contraindications ]. The safety of continuing SOGROYA treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. SOGROYA is not indicated for the treatment of non-GH deficient adults.

Severe Hypersensitivity

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin. Inform patients and/or caregivers that such reactions are possible, and that prompt medical attention should be sought if an allergic reaction occurs. SOGROYA is contraindicated in patients with known hypersensitivity to somatropin or any excipients in SOGROYA [see Contraindications ].

Increased Risk of Neoplasms

Active Malignancy

There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [see Contraindications ]. Any preexisting malignancy should be inactive, and its treatment complete prior to instituting therapy with SOGROYA. Discontinue SOGROYA if there is evidence of recurrent activity.

Risk of Second Neoplasm in Pediatric Patients

In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent growth hormone deficiency (GHD) and were treated with somatropin, an increased risk of second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. Monitor all patients with a history of GHD secondary to an intracranial neoplasm while on somatropin therapy for progression or recurrence of the tumor.

New Malignancy During Treatment

Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting SOGROYA in these patients. If treatment with SOGROYA is initiated, carefully monitor these patients for development of neoplasms.

There is risk of malignant changes of preexisting nevi with somatropin treatment in patients. Monitor patients on SOGROYA therapy carefully for increased growth or potential malignant changes of preexisting nevi. Advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances, and/or changes in the appearance of preexisting nevi.

Glucose Intolerance and Diabetes Mellitus

Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes mellitus has been reported in patients taking somatropin. Patients with undiagnosed pre-diabetes and diabetes mellitus may experience worsened glycemic control and become symptomatic. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or pre-diabetes should be monitored closely. The doses of antidiabetic agents may require adjustment when SOGROYA is initiated.

Intracranial Hypertension

Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in patients treated with somatropin. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, intracranial hypertension-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose.

Perform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating SOGROYA. If papilledema is observed by fundoscopy during SOGROYA treatment, treatment should be stopped. If intracranial hypertension is confirmed, treatment with SOGROYA can be restarted at a lower dose after intracranial hypertension-associated signs and symptoms have resolved.

Fluid Retention

Fluid retention during SOGROYA replacement therapy may occur. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent.

Hypoadrenalism

Patients receiving somatropin therapy who have or are at risk for corticotropin deficiency may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA treatment. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases [see Drug Interactions ].

Hypothyroidism

Undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during treatment with somatropin therapy. Therefore, patients should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

Slipped Capital Femoral Epiphysis in Pediatric Patients

Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Evaluate pediatric patients receiving SOGROYA with the onset of a limp or complaints of persistent hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly.

Progression of Preexisting Scoliosis in Pediatric Patients

Somatropin increases growth rate, and progression of preexisting scoliosis can occur in patients who experience rapid growth. Somatropin has not been shown to increase the occurrence of scoliosis. Monitor patients with a history of scoliosis for disease progression.

Pancreatitis

Cases of pancreatitis have been reported in patients receiving somatropin. The risk may be greater in pediatric patients compared with adults. Consider pancreatitis in patients who develop persistent severe abdominal pain.

Lipohypertrophy/Lipoatrophy

When SOGROYA is administered subcutaneously at the same site over a long period of time, tissue lipohypertrophy or lipoatrophy may result. Rotate injection sites when administering SOGROYA to reduce this risk [see Dosage and Administration ].

Sudden Death in Pediatric Patients with Prader-Willi Syndrome

There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. SOGROYA is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.

Laboratory Tests

Serum levels of inorganic phosphorus and alkaline phosphatase may increase after SOGROYA therapy. Serum levels of parathyroid hormone may increase with somatropin treatment.