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LAGH Therapy in Pediatrics
Long-Acting Growth Hormone Therapy: Best Practices for Pediatrics

Released: August 14, 2023

Expiration: August 14, 2024

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Key Takeaways
  • Three FDA-approved LAGH therapies have demonstrated short-term efficacy and proven to be noninferior compared with daily GH therapy in yielding height velocity in clinical trials.
  • Although the FDA indications for the 3 LAGH therapies range in age at which therapy can be initiated, HCPs should fully consider the risks vs benefits for infants and toddlers with GHD and associated hypoglycemia. 
  • Global, independent, and manufacturer-sponsored registries are necessary to fully understand the long-term risks of LAGH therapy and inform the timing of measurement of IGF-1 following injections.

Daily use of recombinant human growth hormone (GH) has been available for treating children with GH deficiency (GHD) since the 1980s. Yet healthcare professionals (HCPs) must pay strict attention to reinforcing the safety, efficacy, and appropriate use of these therapies among pediatric populations in their clinical practice.

Endocrinologists often have plenty of experience with using GH therapy in patients in their infancy to adulthood. Further, most are comfortable with the safety profile of daily GH therapy in various pediatric patient populations, such as congenital GHD, panhypopituitarism-associated hypoglycemia, and survivors of cancer. This recognized safety profile is a result of the many postmarket phase IV surveillance registries, which have collected nearly 600,000 patient-years of data to assist in understanding the adverse effects of GH therapy.

Common Barriers to Daily GH Therapy

However, the most common challenge I see with prescribing daily GH therapy to pediatric patients is the frequent injections. Even though the needle is small and not very painful, I have seen fatigue among patients the longer they are on therapy. Further, as patients grow and begin to reach their predetermined normal range in response to GH therapy, they may think that they no longer need it or that they cannot feel a difference when they are or are not on treatment. I have also witnessed patients on GH therapy not reach their midparental target height or genetic potential, likely because of challenges with treatment adherence and persistence. Some of these barriers are related to patients’ psychosocial or cultural environments, whereas others are affected by the role insurance plays in their ability to continually access GH therapy. Whether it is insurance-related approvals or denials, medication shortages, or formulary changes, these challenges all affect treatment adherence.

Enter LAGH Therapy

I am excited that the FDA now has approved 3 different once-weekly, long-acting growth hormone (LAGH) therapies (lonapegsomatropin, somapacitan, and somatrogon) for the treatment of children with GHD. Each LAGH therapy has demonstrated efficacy in the short term and has been shown to be noninferior compared with daily GH therapy in yielding height velocity. In addition, some studies have shown that as puberty begins and children approach their near adult height, they are experiencing appropriate height gains with LAGH therapy.

The need now is for safety and efficacy data capture in long-term studies. I am particularly excited for the independent, global effort of GloBE-Reg, where stakeholders from around the world are collaborating to generate comparison data between LAGH and daily GH therapies. These registries will help all stakeholders better understand the long-term efficacy and safety of LAGH therapies.

Differences Among the LAGH Therapies

There are some differences among the LAGH therapies. Once-weekly lonapegsomatropin, somapacitan, and somatrogon each have their own pharmacodynamic and pharmacokinetic profile, which can affect their safety and efficacy profiles. Because of this, I think researchers need to study each LAGH therapy more carefully to fully understand its risks and/or benefits to pediatric patients with GHD. 

Measuring and Monitoring IGF-1 in LAGH Therapy

When monitoring patients receiving LAGH therapy, it is important to look at their weight and height velocity (as we do with daily GH therapy). In addition, HCPs will need to monitor patients’ IGF-1 values, which will require a new paradigm. Although most endocrinologists are familiar with measuring IGF-1 for children receiving daily GH therapy, once-weekly preparations will produce an IGF-1 peak several days after injection that will decrease to a trough before the next injection. Therefore, the average IGF-1 value should be estimated at approximately Day 4 for each LAGH therapy. This value will be close to the average value for the week and will help guide growth, adverse effect management, and treatment response among patients.

With that being said, how HCPs interpret IGF-1 data is important. Should we look at the peak, average, or trough? It is my belief that we should look at the average value because it will most likely correlate with patients’ height outcomes and safety events. The peak value may lead some to inadequately treated patients because they will experience IGF-1 values above +2 standard deviations for brief periods each week. IGF-1 values greater than +2 standard deviations are transient, and it is unlikely that they will be associated with any adverse events. To assist with this, some LAGH manufacturers are developing an algorithm or table to estimate patients’ average IGF-1 value from the measured value and the time since the most recent injection. Eventually, apps could be developed to help with this, too. Regardless, HCPs will need to familiarize themselves with the new process so they can effectively monitor patients’ IGF-1 values.

IGF-1 values may also help inform if a dose adjustment is necessary. Among the various LAGH clinical trials, researchers adjusted patients’ dosage following weight-based recommendations, if an IGF-1 value was too high, or if there were adverse events. Therefore, it will be up to HCPs to learn how to adjust LAGH dosages per patient in their clinical practice when deemed necessary. The process of adjusting the dose will also be different for the LAGH therapies because of differences in the devices.

Adverse Events With LAGH Therapy

Even though researchers have not found clinically relevant neutralizing antibodies in LAGH therapies, except in children with GH gene deletions, it is important that HCPs recognize the potential concern for neutralizing antibodies against the new molecules. In clinical trials, researchers have not seen any new adverse events with use of LAGH therapy compared with daily GH therapy. Finally, we need data to better understand how LAGH therapy affects blood sugar, lipid metabolism, and body composition. And, as mentioned before, registries are key to confirming these data in the long term. 

LAGH Therapy Patient Selection

As HCPs start to have conversations with patients and their caregivers on daily GH vs LAGH therapy, the determining factor will depend on the patients. They will need to determine which therapy best fits their lifestyle to ensure proper adherence and improved outcomes. The only exception to this are infants and toddlers with GHD and associated hypoglycemia—either isolated or because of panhypopituitarism. More data are needed on this population before I can be comfortable prescribing LAGH therapy to them.  

Your Thoughts

I am excited to start offering LAGH therapy to my patients. Reducing the number of prescribed injections from 365 to 52 per year is a huge advantage for patients. The next step, however, is adequate insurance coverage once they approve and update their formularies, which will take time. Hopefully, we will hit a point where all stakeholders recognize LAGH therapy as a standard of care for pediatric patients with GHD.

Are you prescribing LAGH preparations to children in your clinical practice? Join the conversation by commenting in the box below.

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