Error in Table 1, 5th column, 19th row
Table 1.
Overview of the development history of LAGH analogues.
| Company | LAGH analog | Modification to GH molecule | Frequency of administration | Current status | Research data |
|---|---|---|---|---|---|
| Depot Formulation | Depot Chemical | ||||
| Altus Pharmaceuticals | ALTU-238 | Long-extended release formulation using protein crystallization technology (22 kDa) (39) | 7 days | Althea acquired assets in 2010 | No further studies planned |
| Critical Pharmaceuticals | CP016 | Supercritical carbon dioxide, formed when CO2 exceeds its thermodynamic critical point, used to create the depot (22 kDa) (39) | 14 days | Company under liquidation | Evidence of ongoing studies at other corporations |
| Genentech | Nutropin Depot® | Encapsulated in biocompatible, biodegradable, polylactide-coglycolide polymer microsphere (22 kDa) (40) | 14 days | Removed from market (39) | |
| LG Life Sciences, Ltd | Eutropin Plus™ (LB03002) | Microparticles containing GH incorporated into sodium hyaluronate and dispersed in an oil base of medium-chain triglycerides (22 kDa) | 7 days | Marketed in Korea for childhood GHD; approved in Europe but not marketed in the EU | Phase 3 trial in CGHD suggest non-inferiority (41), safety data from a Korean registry database in children with growth disorders (42), Phase 2 trial in children with ISS demonstrated non-inferiority and well-tolerated (43) |
| PEGylated Formulations | PEGylation prolongs in vivo mean residence time of GH, through slowing absorption and protection from proteolysis | ||||
| Ambrx | ARX201 | 30-kDa PEG added to unnatural amino acid incorporated into GH (52 kDa) | 7 days | No longer being developed (39) due to PEGylated-containing vacuoles in the epithelial cells of the choroid plexus in monkeys (44) | |
| Bolder BioTechnology | BBT-031 | Site-specific PEGylated GH analog (not available) | 7 days (planned) | Preclinical studies (45) | |
| GeneScience Pharmaceuticals Co, Ltd | Jintrolong® | 40-kDa PEG attached to GH (62 kDa) | 7 days (13,16) | Marketed in China for CGHD | Phase 3 studies show good IGF-I profile, Phase 4 studies now ongoing |
| Novo Nordisk | NNC126-0083 | 43-kDa PEG residue attached to glutamine 141 (65 kDa) | 7 days | Unsatisfactory IGF-I profile peak and duration (46) | No longer being developed as of 2011 |
| Pfizer | PHA-794428 | Branched 40 kD PEG on N-terminus of GH (62 kDa) | 7 days | High rate of lipoatrophy at injection site (47) | No longer being developed as of 2009 |
| Pro-Drug formulation | Mechanism of conversion to active drug | ||||
| Ascendis | TransCon GH® (ACP-001) | Unmodified rhGH transiently bound to a PEG carrier molecule via a self-cleaving linker that is dependent upon pH and temperature (22 kDa) | 7 days (8, 12, 14, 18, 48) | Phase 2 studies in CGHD and AGHD showed comparable GH and IGF-I profile to daily GH dosing | Completed Phase 3 study in CGHD and data submitted to FDA and EMA |
| Phase 3 studies in CGHD showed positive growth response (49) | Phase 3 study in AGHD currently planned | ||||
| Non-covalent albumin binding GH compound(s) | Albumin binding | ||||
| Novo Nordisk A/S | Sogroya® (NNC0195-0092) | Single-point mutation in GH, with albumin binding moiety attached (non-covalent albumin-binding properties) (50, 51) (23 kDa) | 7 days (52) | Phase 2 studies in CGHD showed comparable IGF-I profile to daily GH dosing (53) | Phase 3 studies in CGHD, Phase 2 studies in SGA |
| Phase 3 studies in AGHD well tolerated (54–56) | |||||
| Approved by the FDA in August 2020 for use in AGHD but not marketed yet | |||||
| GH Fusion Proteins | Protein fused with GH | ||||
| Ahngook Pharmaceutical Co, Ltd | AG-B1512 | Recombinant GH genetically fused to a polypeptide linker and an anti-human serum albumin Fab antibody (~72 kDa) | 14 or 28 days (57) | Preclinical studies show IGF-I level elevation sustained for 20 days | Ongoing research |
| Alteogen | ALT-P1 | rhGH fused with NexP™, recombinant a1-antitrypsin (~74 kDa) (58) | unknown | Stopped Phase 2 study in CGHD (59) | |
| Asterion | ProFuse™ GH | GH binding protein (~82 kDa) (60) | 1 month (planned) | Preclinical studies to provide intravascular stores of inactive GH | |
| Genexine and Handok | GX-H9 | rhGH fused to hybrid non-cytolytic immunoglobulin Fc portions of IgD and IgG4 (100 kDa) (61) | 7-14 days (62) | Phase 2 studies in AGHD completed (63) | Phase 3 studies in CGHD with twice-monthly dosing ongoing |
| Phase 2 studies in CGHD showed reassuring height changes | |||||
| Hanmi Pharmaceutical Co | LAPS rhGH (HM10560A) | Homodimeric aglycosylated IgG4 Fc fragment (~51 kDa) (64) | 7-14 days (64) | Phase 2 in AGHD show good tolerability | Phase 3 studies in AGHD (65) |
| JCR Pharmaceuticals | JR-142 | Engineered hGH fused at C-terminus with modified human serum albumin at N-terminus (~88 kDa) (66) | 7 days | Preclinical trials | Phase 1 study completed (67) |
| OPKO Health and Pfizer | Somatrogon (MOD-4023) | rhGH fused to three copies of carboxyl-terminal peptide (CTP) of hCG β-subunit (47.5 kDa) | 7 days (11, 15) | Phase 2 studies in CGHD (68), Phase 3 studies in AGHD did not meet primary endpoint of truncal fat reduction (17) | Phase 3 study in CGHD completed (69), and extension studies now ongoing |
| Phase 3 studies in CGHD showed non-inferior improvement in height velocity with good tolerability | |||||
| Teva | Albutropin (TV-1106) | Human serum albumin fused to N-terminus of GH (88 kDa) | 7 days (9,10) | Studies in AGHD discontinued for unknown reason; presumed unfavorable benefit:risk profile | |
| Versartis | Somavaratan (VRS-317) | Fusion protein of rhGH and the pharmacologically inactive portion of long chains of natural hydrophilic amino acids (XTEN technology) | 7, 14 or 28 days (22) | No longer being developed as of 2017 as the Phase 3 study did not meet its primary end-point for non-inferiority comparison against daily rhGH for height velocity in CGHD (22) | |
AGHD, adults with GH deficiency; CGHD, children with GH deficiency; EMA, European Medicines Agency; EU, European Union, FDA, Food and Drug Administration; kDa, kilodalton; ISS, idiopathic short stature; PEG, poly(ethylene glycol); rhGH, recombinant human GH; SGS, small for gestational age. Table is modified from Miller BS, et al. (70).
In the original article, there was a mistake in Table 1 as published. In Table 1 , 5th column, 19th row, the company “Alteogen” under the “Current Status” column was incorrectly stated that the company was “bankrupt in 2009”. This statement is incorrect as the company remains a currently viable bio-tech company globally.
The authors apologize for this inadvertent error with the statement and a modified Table 1 is provided below, where the statement “bankrupt in 2009” is now deleted. This new table does not change the scientific conclusions of the article in any way. The original article has been updated.