What are the benefits of Sermorelin (Growth Hormone-Releasing Hormone (GHRH) analog) for individuals with growth hormone deficiency?

Sermorelin Benefits in Growth Hormone Deficiency

Sermorelin is effective for promoting growth in select prepubertal children with documented growth hormone deficiency, particularly those with hypothalamic dysfunction, though recombinant growth hormone (rhGH) remains the superior and preferred treatment option.

Diagnostic Use

Sermorelin serves as a reliable diagnostic tool for identifying growth hormone deficiency when administered as a single intravenous dose of 1 μg/kg. 1

• The test produces fewer false-positive results compared to other provocative tests, making it more specific for diagnosing GH deficiency 1
• However, normal GH responses to sermorelin cannot exclude hypothalamic-origin GH deficiency, requiring confirmation with additional provocative tests 1
• The combination of sermorelin with arginine may provide even greater diagnostic specificity, though this requires further validation in pediatric populations 1

Therapeutic Benefits in Children

Growth Promotion Effects

Sermorelin at 30 μg/kg/day via subcutaneous injection at bedtime increases height velocity in prepubertal children with idiopathic GH deficiency. 1

• Height velocity increased from baseline 3.3 cm/year to 6.0 cm/year after one year of treatment in children with radiation-induced GH deficiency 2
• In another cohort, 8 of 18 GH-deficient children showed worthwhile responses with height velocity increases exceeding 2 cm/year (range 2.7-11.2 cm/year) 3
• Growth acceleration was sustained for 12 months in clinical trials, with limited data suggesting maintenance up to 36 months 1
• Sermorelin induced catch-up growth in the majority of treated GH-deficient children 1

Patient Selection for Optimal Response

Children who are slower growing, shorter, with delayed bone age and height age demonstrate the best therapeutic response to sermorelin. 1

• Pretreatment peak serum GH response above 30 mU/L during intravenous GHRH testing predicts good growth response, though lower peaks do not exclude potential benefit 3
• In children who previously received human GH, height velocity on hGH correlated with response to sermorelin 3

Specific Advantages in Radiation-Induced GH Deficiency

Sermorelin maintained or improved leg length in children who received craniospinal irradiation, addressing a specific complication of this treatment. 2

• This benefit is particularly relevant since craniospinal irradiation causes disproportionate growth impairment of the spine 2
• Treatment should begin at least 2 years post-radiotherapy in prepubertal children 2

Comparative Effectiveness

Sermorelin vs. Recombinant Growth Hormone

Sermorelin produces inferior growth responses compared to standard recombinant GH therapy and should not be considered first-line treatment. 1, 2

• Height velocity with sermorelin 30 μg/kg/day (whether as continuous infusion or divided doses) was consistently less than with once-daily subcutaneous somatropin 30 μg/kg/day 1
• After one year of sermorelin (height velocity 6.0 cm/year), switching to GH therapy increased height velocity to 7.5 cm/year 2
• The effect of long-term sermorelin treatment on final adult height remains undetermined 1

Safety Profile

Sermorelin demonstrates excellent tolerability with minimal adverse effects. 1, 2, 3

• Transient facial flushing and injection site pain are the most commonly reported adverse events 1
• No adverse changes in biochemical or hormonal parameters were observed during treatment 2
• Anti-GHRH antibodies developed in 14 of 18 patients in one study but did not adversely affect growth or GH responses 3
• No evidence of priming or desensitization effects on GH responses with continued therapy 3

Critical Limitations and Caveats

Four major limitations restrict sermorelin's clinical utility:

1. Incomplete efficacy: Some patients (4 of 14 in one study) showed growth deceleration on sermorelin for unknown reasons, despite previous response to hGH 3

2. Lack of long-term outcome data: The impact on final adult height has not been established 1

3. Requirement for twice-daily injections: This dosing schedule (compared to once-daily GH) may reduce adherence 1, 3

4. Limited to hypothalamic dysfunction: Sermorelin requires intact pituitary function and is ineffective in primary pituitary GH deficiency 1

Current Clinical Context

Growth hormone therapy is the established standard of care for documented GH deficiency, with treatment initiated when height falls below the 3rd percentile AND height velocity is below the 25th percentile. 4, 5

• Diagnosis must be confirmed through appropriate GH-stimulation tests using validated cut-points before initiating any GH-related therapy 4
• Standard rhGH dosing is 0.045-0.05 mg/kg/day by daily subcutaneous injection 6
• Treatment continues until height velocity drops below 2 cm/year or epiphyseal growth plates close 5, 7

Given the superior efficacy of recombinant GH and the lack of definitive long-term outcome data for sermorelin, rhGH remains the preferred therapeutic option for all forms of documented GH deficiency. 6