Inhaled Human Growth Hormone

Inhaled hGH was under development by Alkermes/Lilly [5]. One-month and 6-month inhalation toxicology studies were carried out in cynomolgus monkeys with no adverse effects in the lung observed. These studies supported clinical trials in normal volunteers. The trial was a crossover design in 12 young adult subjects, each subject receiving both subcutaneous and inhaled hGH on separate days. Inhaled hGH was well tolerated with no coughing or adverse taste issues. Pulmonary function and vital signs were measured with no apparent changes of clinical significance. The PK profiles for sc injection (4 mg hGH) and inhalation delivery (92 mg hGH in 4 dry powder capsules) were quite similar as seen in Figure 1.2 Overall delivery efficiency was approximately 5% compared to sc delivery, somewhat less than the approximately 10% values observed for a similar dry powder formulation and delivery system for inhaled insulin. The decreased efficiency with respect to inhaled insulin was expected because of the greater molecular weight of hGH.

Following the demonstration of safety in normal young adults, a similar crossover study was carried out in pediatric patients. Again, there were no adverse clinical outcomes for inhaled delivery, PK profile was similar to that from sc delivery, but overall delivery efficiency was less than the business development goal of 5% relative to sc delivery. With this result, the program was terminated.

If manufacturing costs of hGH can be reduced, inhaled delivery of hGH could be considered to improve compliance in children and increase the willingness of parents to start therapy in their children since reluctance to start injections is a negative factor in initiating growth hormone therapy.

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