Serostim® (somatropin) for injection Clinical Trial Results

Mixed ethnicity male in hat taking a selfie in front of a wooded forest, not actual Serostim® patient

Clinical Trial Results

Statistically significant improvements in the 3 key symptoms of HIV‑associated wasting¹

The clinical efficacy of Serostim^® was assessed in 2 randomized, double-blind, placebo-controlled trials. All patients participating in the clinical trials received concomitant antiretroviral therapy.

In 2 clinical trials, Serostim^® has proven efficacy in treating the 3 key symptoms of HIV‑associated wasting

Clinical Trial 1

Serostim^® showed statistically significant increases in LBM, body weight, and improvements in physical endurance

P < 0.001, P = 0.011, and P = 0.039, respectively

Study design

12-week, randomized, double-blind, placebo-controlled study followed by an open-label extension phase
178 patients with severe HIV‑associated wasting taking nucleoside analogue therapy (pre–highly active antiretroviral therapy [HAART] era)
Primary endpoint: body weight (BW)
Body composition assessed using dual energy X-ray absorptiometry (DXA) and physical function assessed by treadmill exercise testing
Patients treated with:
- Placebo
- Serostim^® 0.1 mg/kg daily
96% were male
The average baseline CD4 count/microliter was 85
140 patients completed the 12-week course of treatment and were at least 80% compliant with the study drug

LBM and Body Weight¹
Physical Endurance¹

Serostim^® increased LBM and weight

After 12 weeks of treatment:

3.10 kg (6.80 lb) mean increase in LBM with Serostim^® (n=70) vs. placebo (n=71) P < 0.001

1.60 kg (3.50 lb) mean increase in body weight with Serostim^® (n=70) vs. placebo (n=71) P = 0.011

Mean decrease in body fat was significantly greater with Serostim^® (n=70) vs. placebo (n=71)
P < 0.001

There were no significant changes with continued treatment beyond 12 weeks, suggesting that the original gains of LBM and body weight were maintained.

Click here for data

Serostim^® improved physical endurance

Median treadmill work output after 12 weeks of once-daily treatment with Serostim® (P = 0.039) or a placebo:

Placebo (n = 71)
No improvement in physical endurance

Serostim^® (n = 70)
13% improvement in physical endurance

Changes in treadmill performance were significantly correlated with changes in LBM.

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Clinical Trial 2

Serostim^® provided improvements in LBM, body weight, and physical endurance*

*P < 0.01 for mean change in physical endurance vs placebo.

Study design

12-week, randomized, double-blind, placebo-controlled study
757 patients with HIV‑associated wasting
Primary efficacy endpoint: physical function as measured by cycle ergometry work output
Body composition assessed using bioelectrical impedance spectroscopy (BIS) and DXA
Patients treated with:
- Placebo
- Serostim^® 0.1 mg/kg every other day
- Serostim^® 0.1 mg/kg daily
91% of patients were male
88% of patients were treated with HAART
Average baseline CD4 count/microliter was 446
646 patients completed the 12-week, placebo-controlled phase and continued in an open-label extension phase of the trial

LBM and Body Weight¹
Physical Endurance¹
Patients' Perceptions¹

Serostim^® increased LBM and body weight

After 12 weeks of treatment, the average increase in LBM and total body weight was significantly greater in both Serostim^® groups vs the placebo group.

Bar chart showing results of lean body mass and body weight from Clinical Trial 2: a 12-week, randomized, double-blind, placebo-controlled study

Patients treated through week 24 of the extension phase improved further or maintained their increases in LBM and body weight

All patients (n = 646) completing the 12-week, placebo-controlled phase of Clinical Trial 2 continued Serostim^® treatment into an extension phase. 548 of these patients completed an additional 12 weeks of active treatment. In these patients, changes in LBM, body weight, and fat mass either improved further or were maintained with continued Serostim^® treatment.

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Serostim^® improved physical endurance

After 12 weeks of treatment, physical endurance improved approximately 9% in both Serostim® treatment arms and decreased < 1% in the placebo group.

Bar chart showing results of physical endurance from Clinical Trial 2: a 12-week, randomized, double-blind, placebo-controlled study

Improvements with Serostim^® were maintained or increased through week 24 of the extension phase

All patients (n=646) completing the 12-week, placebo-controlled phase of Clinical Trial 2 continued Serostim^® treatment into an extension phase. 548 of these patients completed an additional 12 weeks of active treatment. In these patients, changes in cycle ergometry work output, LBM, body weight, and fat mass either improved further or were maintained with continued Serostim^® treatment.

Click here for data

Patients’ perceptions of the impact of 12 weeks of treatment on their wasting symptoms as assessed by the Bristol-Meyers Anorexia/Cachexia Recovery Instrument improved with both doses of Serostim^® in Clinical Trial 2.

Adverse reactions in clinical trials

In Clinical Trial 2 of patients with HIV‑associated wasting or cachexia, the most commonly reported adverse reactions with Serostim^® (0.1 mg/kg daily) were1:

Musculoskeletal discomfort
Increased tissue turgor (particularly of the hands or feet)

Dose reductions were required in 23% of patients taking Serostim^® 0.1 mg/kg daily and in 11% of patients taking Serostim^® 0.1 mg/kg every other day.

Discontinuations as a result of adverse reactions:

10.3% (Serostim^® 0.1 mg/kg daily)
6.6% (Serostim^® 0.1 mg/kg every other day)

The most common reasons for dose reduction and/or drug discontinuation were arthralgia, myalgia, edema, carpal tunnel syndrome, elevated glucose levels, and elevated triglyceride levels.

Controlled Clinical Trial 2 adverse reactions occurring in at least 5% of patients in 1 of the treatment groups, and at an incidence greater than placebo

	Placebo	Serostim^® 0.1 mg/kg every other day	Serostim^® 0.1 mg/kg daily
	(n=247)	(n=257)	(n=253)
Body System Preferred Term	%	%	%
Musculoskeletal System Disorders
Arthralgia	11.3	24.5	36.4
Myalgia	11.7	17.9	30.4
Arthrosis	3.6	7.8	10.7
Gastrointestinal System Disorders
Nausea	4.9	5.4	9.1
Body as a Whole – General Disorders
Peripheral edema	2.8	11.3	26.1
Fatigue	4.5	3.5	5.1
Endocrine Disorders
Gynecomastia	0.4	3.5	5.5
Central and Peripheral Nervous System Disorders
Paresthesia	4.5	7.4	7.9
Hypoesthesia	2.4	1.6	5.1
Metabolic and Nutritional Disorders
Generalized edema	1.2	1.2	5.9

These are not all the possible side effects of Serostim^®. Counsel your patients to speak with you about any side effects they are experiencing. Please see the Serostim^® full Prescribing Information and Important Safety Information.

Recommended dosage and administration for treatment with Serostim^®

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Key insights from HCPs who have experience treating with Serostim^®

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References:

Serostim^® (somatropin) for injection [prescribing information]. Rockland, MA: EMD Serono, Inc.

Important Safety Information and Indication

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CONTRAINDICATIONS

Acute Critical Illness: Serostim^® (somatropin) should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure.

Active Malignancy: Somatropin is contraindicated in the presence of active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Discontinue somatropin if there is evidence of recurrent activity.

Hypersensitivity: Serostim^® is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Systemic hypersensitivity reactions have been reported.

Diabetic Retinopathy: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.

WARNINGS AND PRECAUTIONS

Acute Critical Illness: Increased mortality (42% vs 19% in somatropin compared to placebo treated) in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin.

Concomitant Antiretroviral Therapy: Somatropin has been shown to potentiate HIV replication in vitro, and there was no increase in virus production when antiretroviral agents were added to the culture medium. No significant somatropin-associated increase in viral burden was observed. All patients received antiretroviral therapy for the duration of treatment during Serostim^® clinical trials.

Neoplasms: Patients with preexisting tumors should be monitored for progression or reoccurrence. Monitor patients on somatropin therapy carefully for preexisting nevi.

Impaired Glucose Tolerance/Diabetes: Patients with other risk factors for glucose intolerance should be monitored closely during Serostim^® therapy. Cases of new onset impaired glucose tolerance, new onset type 2 diabetes, and exacerbation of preexisting diabetes have been reported in patients receiving Serostim^®. Some patients developed diabetic ketoacidosis and diabetic coma and, in some, improved when Serostim^® was discontinued and in others persisted. Some of these patients required initiation or adjustment of antidiabetic treatment.

Intracranial Hypertension: Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported usually within the first 8 weeks of somatropin therapy and rapidly resolved after stopping or reducing the somatropin dose. Funduscopic examination should be performed prior to initiating treatment with somatropin and periodically during treatment. If papilledema is observed, treatment should be stopped and restarted at a lower dose after IH-associated symptoms have resolved.

Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs.

Fluid Retention/Carpal Tunnel Syndrome: Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Serostim^®, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing. Carpal tunnel syndrome may occur and if the symptoms of carpal tunnel do not resolve by decreasing the weekly number of doses, it is recommended that Serostim^® treatment be discontinued.

Skin Atrophy: Rotate the injection site to avoid tissue atrophy.

Pancreatitis: Cases of pancreatitis have been reported rarely. Consider pancreatitis in patients who develop persistent severe abdominal pain.

ADVERSE REACTIONS

In clinical trials in HIV‑associated wasting or cachexia the most common adverse reactions (incidence >5%) were arthralgia, myalgia, peripheral edema, arthrosis, nausea, paresthesia, generalized edema, gynecomastia, hypoesthesia and fatigue.

SPECIAL POPULATIONS:

Somatropin should be used during pregnancy only if clearly needed and with caution in nursing mothers because it is not known whether somatropin is excreted in human milk. The safety and effectiveness of somatropin in pediatric patients with HIV have not been established. Clinical studies did not include sufficient numbers of subjects > 65 to determine a response different from that of younger patients. Studies have not been conducted in patients with hepatic or renal impairment. Gender-based analysis is not available.

INDICATIONS AND USAGE

Serostim^® (somatropin) for injection is indicated for the treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance. Concomitant antiretroviral therapy is necessary.

Please click here for full Prescribing Information.