Key Clinical Summary: Transitioning Patients from Daily to Long-Acting Growth Hormone (LAGH)

This is a micro-learning module summary of the LAGH Education session which you can find here.

Before participating please read our CME and disclosure information which can be found here. This program was supported by an independent medical education grant from Novo Nordisk. This content is intended for US Healthcare Professionals only.

Introduction:

This summary provides an overview of the transition from daily growth hormone (GH) to long-acting growth hormone (LAGH) preparations for patients with GH deficiency (GHD). Daily GH has been a standard of care for over 30 years, but its effectiveness is often compromised by high rates of non-adherence in both children and adults, with some studies showing non-adherence rates as high as 60%. The primary motivation for developing weekly LAGH therapies is to reduce the burden of daily injections, with the goal of improving adherence and potentially treatment outcomes. While LAGH therapies offer convenience, clinicians must understand their unique pharmacological profiles, select appropriate candidates, and employ specific monitoring strategies to ensure optimal and safe outcomes.

Adherence Challenges with Daily GH:

Non-adherence to daily GH is a significant clinical problem driven by multiple factors beyond the simple inconvenience of injections. Understanding these barriers is crucial when considering a switch to LAGH.

• Injection-Related Issues: Patients often report daily injections as inconvenient, painful, and a source of distress for themselves and caregivers, leading to "treatment fatigue".
• Psychosocial Factors: Deeper-seated issues often contribute to non-adherence, including a fear of long-term side effects, a lack of belief in the treatment's benefits, and the attitude of the treating physician towards the therapy.
• Patient Perceptions: Younger adults may perceive daily injections as a "lifestyle limitation" and tend to be less adherent than older adults, who are often more accepting of regular medication routines.
• Key Takeaway: Reducing injection frequency with LAGH may address some adherence barriers, but it won't solve underlying patient concerns.

Effective education and communication are critical to address fears, manage expectations, and reinforce the benefits of consistent therapy.

Understanding LAGH Preparations:

Three primary LAGH preparations are available, each utilizing a different technology to extend its half-life. It's important to recognize that neither daily nor LAGH therapies perfectly replicate the body's natural, pulsatile GH secretion.

• Mechanisms of Action:
• Somapacitan: A small albumin-binding molecule is reversibly attached to GH, reducing its clearance and extending its half-life.
• Lonapegsomatropin: A prodrug that binds an inert carrier to the GH molecule, shielding it from clearance until it is predictably released under physiological conditions.
• Somatrogon: A fusion protein that combines the GH molecule with copies of the C-terminal peptide (CTP) from hCG, which extends its half-life.
• Pharmacodynamic Profile: Unlike the relatively stable IGF-1 levels seen with daily GH, weekly LAGH injections create a distinct cycle. This fluctuating profile is the most critical difference and directly impacts monitoring strategies.

Selecting Appropriate Candidates for LAGH Therapy:

A case-by-case assessment is essential to identify patients who are most likely to benefit from switching to LAGH.

• Good Candidates May Include:
• Naïve patients considered at high risk for non-adherence, such as those already managing multiple other daily injections.
• Motivated patients whose busy lifestyles make daily injections challenging.
• Transition patients and adults with no prior history or significant risk of cancer.
• Patients with normal to mildly impaired glucose tolerance and minimal to no residual tumor.
• Use with Caution and Individual Assessment:
• Patients with a history of childhood cancer or other malignancies, even if in remission, require careful consideration due to the lack of long-term safety data.
• Patients with a notable residual tumor also warrant a cautious approach.
• Not Recommended For:
• Use is generally not recommended in patients with active malignancy, severe liver impairment, or for off-label purposes such as fertility, pregnancy, anti-aging, or sports performance enhancement.

Monitoring and Adjusting LAGH Therapy:

Effective management of LAGH therapy requires a departure from the monitoring practices used for daily GH.

• IGF-1 Monitoring is Time-Critical: The primary goal is to estimate the average weekly IGF-1 level.
• Blood samples should be drawn at a specific time point post-injection:
• Day 4 for somapacitan and somatrogon, and Day 4.5 for lonapegsomatropin.
• If a sample is taken outside this window, product-specific correction factors must be applied to the IGF-1 result to accurately estimate the weekly average and guide dose adjustments. The further the sample time is from the ideal window, the greater the uncertainty.
• The therapeutic goal is to adjust the dose to maintain the average IGF-1 SDS within the normal range (typically between -2.0 and +2.0).
• Dosing and Titration:
• In adults, starting doses are typically fixed and are not weight-based.
• Lower starting doses are recommended for older patients and those at risk for glucose intolerance. Higher doses may be needed for younger patients and women on oral estrogen.
• Crucially, direct mg-for-mg dose comparisons between different LAGH formulations or with daily GH are inappropriate due to their unique molecular weights and pharmacokinetic/pharmacodynamic profiles.
• Holistic Assessment: In addition to IGF-1 levels, clinicians must monitor for clinical efficacy, side effects, and potential impacts on other hormone replacements (e.g., cortisol, thyroxine).

Conclusion:

Approved LAGH preparations offer a non-inferior and comparably safe alternative to daily GH, with the primary advantage of reducing injection frequency to improve adherence. Successful implementation in the clinic hinges on careful patient selection, a thorough understanding of the unique pharmacodynamics of each agent, and a new, time-sensitive approach to IGF-1 monitoring. Open communication and patient education are essential to manage expectations regarding both the benefits and the specific monitoring requirements of these newer therapies. While promising, longer-term, real-world data are still needed to fully establish the impact of LAGH on adherence, quality of life, and long-term safety, particularly in specific populations like cancer survivors.