Back Back
Strategies to Incorporate LAGH Therapy
Incorporating Long-Acting Growth Hormone Therapy Into Practice

Released: July 26, 2023

Expiration: July 26, 2024

Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Randomized controlled clinical trials demonstrate that some long-acting growth hormone treatments are noninferior to daily growth hormone and offer the potential for improved treatment adherence among patients.
  • Long-acting growth hormone therapy comes with its own set of barriers and challenges, such as cost and the need for robust registries to assess long-term benefits and potential side effects.
  • To help discover new ways to make growth hormone deficiency (GHD) therapy more accessible to patients who need it, endocrinologists should be educated on GHD and available treatment options.

Growth hormone (GH) must be given via subcutaneous injection, and over the last 35 years, the delivery system using prefilled syringes has improved treatment options greatly. Furthermore, the medical community has long recognized the need for a long-acting growth hormone (LAGH) preparation.

Initial LAGH preparations were depot injections. Due to varying industry- and marketing-related issues, these products were withdrawn from production. However, novel approaches to growth hormone therapy have resulted in long-acting preparations in aqueous solution that are comparable to treatment with daily GH. There are currently 3 FDA-approved LAGH preparations in the US, lonapegsomatropin (for children with GHD), somapacitan (for both adults and children with GHD), and somatrogon (for children with GHD). These drugs have been shown to be noninferior to daily growth hormone treatment in randomized, controlled trials.

Daily vs Weekly Preparation

The key theoretical advantage to LAGH injections is increased treatment adherence. When prescribing a daily drug, healthcare professionals (HCPs) want to believe that patients are compliant with the medication as prescribed, but busy schedules and the need for a daily injection can create barriers to compliance. Many people do not want to be burdened with daily injections even though they would greatly benefit from the therapy. I think having the option of a weekly LAGH preparation, given in the same way as the daily option, is a game changer for many patients—those who refused to take GH therapy in the first place and those who miss enough doses to not benefit from daily treatment.

The caveat here is if patients miss a weekly dose of LAGH, they miss treatment for the entire week. I do not think someone who is incredibly noncompliant already would be a candidate for LAGH either. From my clinical experience, I often prescribe bisphosphonate therapy for osteoporosis. The most common drug that we use is administered to patients once a week. Compliance with weekly bisphosphonate therapy is not always ideal, so HCPs must pay close attention to what their patients’ compliance rate will be for LAGH.

Potential Challenges With LAGH

As with any new drug, LAGH preparations may have side effect profiles that differ from daily injections. Thus far in clinical trials, there have yet to be any novel side effects with short-term treatment. But this is something all HCPs should be concerned about because the serum profiles of LAGH and insulin-like growth factor 1 (IGF-1) levels are different. In addition, I think there are some healthy concerns as to whether the pharmacokinetics of LAGH could lead to acromegaly-related changes over a longer period of time.

Registry Studies

The key to better understanding the safety of both daily and LAGH in children and adults will be robust registry studies. For example, GloBE-Reg is an international registry for post-regulatory studies on pediatric growth hormone with daily and long-acting therapies. Adult-based registries in GLoBE-Reg are being structured in a similar way. With these registries, the medical community can capture side effects related to LAGH preparations. Even though this will require the prescribing HCPs to complete forms and report side effects regularly, registries are vital to learning more about and verifying the safety of these products, especially for those patients who will use growth hormone throughout their lifetime.

Dosing and Measuring IGF-1 Levels

When starting someone on growth hormone, HCPs should first prescribe a lower dose, gradually increasing that dose until the patient’s IGF-1 levels are in what is considered the therapeutic range. In my practice, I try to get an IGF-1 standard deviation score between 0 and +2. I avoid scores above +2 because I do not want patients to have an abnormally high IGF-1 level for a long time. I use the IGF-1 level as a biomarker for potential danger, in addition to assessing how the patient is feeling and any changes in waist circumference, energy levels, or exercise.

The other novel issue with LAGH is when to  measure IGF-1 levels. Currently, I advise patients to take their growth hormone on the day they measure their IGF-1 level. With LAGH, the medical community still needs to find the right time to measure IGF-1 levels for safety and efficacy purposes. In LAGH clinical trials, patients had their IGF-1 measured 2 to 4 days after their weekly injection. This may make it more difficult for patients who will now need to time their blood tests more carefully.

Cost

Another potential issue with LAGH is cost. Drug pricing is something that is always mysterious to both patients and HCPs. Although most payers offer daily growth hormone for people who have documented GHD, it often comes with a high co-pay. The question of affordability is going to be important. Further, this is not going to be generalizable because people have varying health coverage from different payers. It is not clear if all insurers will offer LAGH to patients with GHD, especially if the LAGH is more costly.

Other Considerations for GHD Therapy

GHD was a hot topic 30 years ago, but since then endocrinology has become more focused on type 2 diabetes and obesity. Further, GHD is relatively rare and treating it is expensive and time consuming. No matter the practice setting, I think HCPs need be better educated about GHD to help discover how we can make accessing it easier for those who need it. Moreover, this treatment should not be prescribed for people who do not need it, including those who use it as an enhancer for athletic performance or as an antiaging elixir. It is critical that growth hormone is provided appropriately to the patients who need it.

Your Thoughts?

Are you prescribing LAGH preparations in your clinical practice? Join in the conversation by answering the polling question and posting a comment in the discussion section below.

Continue

Poll

1.

Are you prescribing LAGH preparations in your clinical practice?

Submit