New weekly growth hormone injections: the gospel of AGHD for adults and children

The International Endocrinology Society (ICE) and the American Endocrinology Society (ENDO) Joint Conference (ICE/ENDO2014) were held in Chicago, USA from June 21st to 24th, 2014.

According to a study published in ICE/ENDO 2014, Novo Nordisk's weekly new growth hormone injection formulation, NNC0195-0092, is available for the treatment of adult growth hormone deficiency (AGHD) patients with dose response and tolerance. The sex is superior to the daily growth hormone injection preparation (Norditropin Nordiflex, Novo Nordisk Pharmaceuticals).

NNC0195-0092 aims to reduce the number of subcutaneous injections and is one of the few long-acting growth hormone drugs currently being developed worldwide. Its main developer said that Phase 3 clinical trials of NNC0195-0092 are planned, and because long-acting growth hormone preparations are more attractive to children, Phase 3 clinical trials will be conducted in children with AGHD.

This report is a 4-week randomized, open-label, active control phase 1/2 clinical trial. 24 adult ADHD patients aged 20-70 years old discontinued existing growth hormone 14 days before enrollment. drug. There were 4 NNC0195-0092 dose groups: 0.02, 0.04, 0.08 and 0.12 kg/mg. The primary endpoint was safety and the secondary endpoint was pharmacokinetics and pharmacodynamics. In the end, 30 patients completed the trial, 8 in the control group and 22 in the experimental group.

Overall no serious security incidents occurred. There were no adverse reactions in the two NNC0195-0092 low-dose groups; the most common adverse events in the high-dose group were peripheral edema, headache, and knee pain, similar to the adverse effects of conventional high-dose growth hormone formulations.

All doses of NNC0195-0092 increased insulin-like growth factor 1 (IGF-1) levels in AGHD patients (IGF-1 is a growth hormone therapy surrogate effect marker) with a dose-dependent effect. There was no significant difference in the effect of low doses of NNC0195-0092 and daily growth hormone injection preparations on IGF-1.

Two other long-term human growth hormone preparations, VRS-317 (California biotechnology company Versartis) and MOD-4023 (OPKO Health), were also released at the conference.

VRS-317 is a new type of recombinant human growth hormone (rhGH), which was included in the repeated dosing trial of 64 pre-pubertal AHDD patients (mean age 7.8 years), randomized to receive 5.0 mg/kg per month, 2.5 mg every 15 days. /kg or 1.15 mg/kg per week for a total treatment dose of 3 mg/kg for 6 months. The results of the trial showed that the primary end point—the patient's height growth rate within 6 months was comparable to the highest approved doses of Norditropin and Genotropin (Pfizer). It is safe and well tolerated and can significantly increase baseline IGF-1 levels in patients. The drug manufacturer will apply to the FDA at the end of this year to continue the phase 3 clinical trial of the drug.

The clinical trial of MOD-4023 was performed in 56 pre-pubertal AHDD patients, divided into three dose groups of 0.25, 0.48, and 0.66 mg/kg per week, with hGH (34 μg/kg/day) once daily as a control. The pharmacokinetic and pharmacodynamic results of the three dose groups were superior to the control group and showed the potential to promote normal growth. A pivotal phase 3 clinical trial of the drug has been initiated in adult AHDD patients and a similar study will be conducted in children with AHDD in the short term.

Compiled from:
1.Joint Meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014; June 22-23, 2014. Abstract LBSU-0377, Abstract MON-0147, Abstract MON-0149
2. Once-Weekly Growth Hormone Treatment Feasible in Adults, Kids. Medscape. Jun 25, 2014.