Letter to the Editor From Malozowski: “Weekly Lonapegsomatropin in Treatment-naïve Children with Growth Hormone Deficiency: the Phase 3 heiGHt Trial”

The Thornton et al. study (1) formally explored whether a long-acting human growth hormone (LAGH) would increase treatment adherence when compared with daily growth hormone (GH) dosing. Adherence was defined as the ratio of total number of administered to planned doses assessed by drug accountability records and patient diaries. The study was properly designed and successful in showing equivalence in promoting statural growth, replicating prior studies with other LAGHs (2), but surprisingly failed to show differences in adherence—99.6% for the daily injections and 98.6% for the LAGH—thereby scientifically rejecting the hypothesis of increased LAGH compliance and disputing this strong held belief of better adherence.

The authors, while endorsing the efficacy outcome, however, simultaneously disregarded and rejected their own adherence findings stating [sic] “…high levels of adherence are anticipated in a controlled clinical trial and may not be reflective of a real-world setting. The decrease in the number of injections is expected to reduce the overall treatment burden and may improve adherence in a real-world setting, potentially translating to improved overall outcomes.”

The authors fail to report that the real-world hypothesis they advance was rejected almost 20 years ago after expensive drug development and sustained marketing efforts stopped when a similar formulation to lonapegsomatropin—with fewer injections per month than this LAGH (2)—was discontinued for lack of sales (3). Instead, to support the adherence hypothesis they provide 3 references. The first (4) pertains to a nonreal-world manuscript where compliance on GH injections in adults was assessed in a clinical study comparing daily with 3 times a week dosing. Numerically differences were reported but compliance was not statistical different between approaches. Thus, Thornton et al. once more replicated this lack of differences both in well-designed studies and in the real world, a finding that they reject. The other two “real-world” references provided are reviews (5, 6), none on GH or in pediatric populations. One lacks information on injectables while the other has a meager number of injectables. Additional shortcomings listed in these manuscripts include potential for publication bias, lack of adjustment for confounding factors or to investigate any interactions, relaying on prescription filled to assess adherence lacking information on their use, and many others. Hence, none of these 3 references provides any credible information related or relevant to the advanced hypothesis.

Although the desire of patients and parents to get fewer injections is understandable, the terms preference and adherence are unique and distinct, and should not be conflated. It was somewhat surprising that the authors appeared to accept some results, but at the same time reject results that appear of equal value and would have one arrive at a different conclusion. Thus, one can argue the conclusions made were not based on all the data available. In a time where the value of science is questioned by many, it is critical to adhere to the outcomes of well-designed studies and provide all evidence in support of or against one’s data in arriving at conclusions. Only in this way, do we adhere to rigor and reproducibility as required.

Glossary

Abbreviations

GH

growth hormone

LAGH

long-acting human growth hormone

Disclaimer

The views expressed in this letter are those of the author and do not represent an official position of the Department of Health and Human Services.

Additional Information

Disclosures: The authors have nothing to disclose.