Table 1.
–Peptide therapeutics in clinical trials or on the market
| Peptide | Molecular Weight (Da) | Indication | Manufacturer | Drug Name | Oral Delivery Technology | Trial Status | Relevancy to Pediatric Medicine |
|---|---|---|---|---|---|---|---|
| Cyclosporin | 1202.6 | Immunosuppressant (systemic) | Novartis | Neoral (previous form: Sandimmune) | Cyclic peptide, spontaneous microemulsion | FDA-Approved | Yes, studied in pediatric transplant patients aged 0.6–16 yrs (FDA doc) |
| AbbVie Inc | Gengraf | Sold as capsules or solution that contain the microemulsion | FDA-Approved | ||||
| Exenatide | 4186.6 | Glucagon-like peptide-1 analogue for T2D | Oramed Pharmaceuticals, Inc. | ORMD 0901 | Protein Oral Delivery (POD) technology: coated capsule, protease inhibitors, absorption enhancer (unspecified) | Preclinical/Investigational New Drug (Phase 1B); pharmacokinetic study completed in T2D patients, further bioavailability studies planned for 2020 | Trials for treatment of extreme obesity in older children (12–18) |
| Octreotide | 1019.2 | Synthetic somatostatin analog for treatment of acromegaly | Chiasma | Mycappsa (formerly Octreolin) | Transient Permeation Enhancer (TPE): multiple excipients create a lipophilic suspension of hydrophilic particles in hydrophobic medium | FDA-Approved | Case reports of treatment of GI bleeding, hyperinsulinism, hypothalamic obesity |
| Semaglutide | 4113.6 | GLP-1 receptor agonist for T2D | Novo Nordisk | Rybelsus | Eligen Technology licensed from Emisphere Technologies, Inc.: SNAC as a permeation enhancer | FDA-Approved | Investigated for weight management in obese adolescents |
| Insulin | 5808.0 | Regulate blood sugar for T1/T2 diabetes | Oramed | ORMD-0801 | POD technology | Phase 2 trials in progress for both T1D and T2D patients | T1D prevalence rate is 0.3% among children 0–19 years; insulin is standard treatment |
| Novo Nordisk (license acquired from Merrion Pharmaceuticals) | OI338GT | Gastro-Intestinal Permeation Enhancement Technology (GIPET): coated capsule with sodium caprate as a permeation enhancer | Phase 2 trials completed, but product development was discontinued due to high doses making it not commercially viable | ||||
| Oshadi Drug Administration, Ltd | Oshadi Icp | Silica nanoparticles with a branched polysaccharide and a suspension of insulin, proinsulin, and C-peptide in a mixture of oils | Phase 1 and 2 completed | ||||
| Biocon | Tregopil (IN-105) | Insulin analogue with covalent PEG modification for stability and solubility in the GI tract | FDA Phase 1 trial paused in 2018; Phase 2 and 3 trials ongoing in India | ||||
| Diasome | Oral-HDV insulin | Hepatic delivery vesicles (HDV): phospholipid nanocarriers with surface-bound insulin and specific hepatocyte targeting molecules | Phase 2b trial in progress | ||||
| Salmon calcitonin | 3431.9 | Hormone that reduces blood calcium for treatment of Paget’s disease, osteoporosis, hypercalcemia | R-Pharm JSC | TBRIA | Peptelligence (Enteris Biopharm) technology: citric acid | Phase 3 trial completed | Has been used in pediatric patients to treat hypercalcemia, but very rarely |
| Nordic Biosciences | SMCC021 | Eligen Technology from Emisphere Technologies, Inc.: 5-CNAC as a permeation enhancer | Phase 3 trial did not achieve primary endpoint of decreased incidence of bone fractures | ||||
| Leuprolide | 1209.4 | Hormone used to treat endometriosis, prostate cancer, premature puberty | Enteris Biopharma | Ovarest | Peptelligence (Enteris Biopharm) technology: surfactant permeation enhancer and citric acid | Phase 2 trial completed | Premature puberty affects 1 in 5–10,000 children and is often treated with injected hormones |
Abbreviations: FDA – US Food and Drug Administration, GI – gastrointestinal tract, GIPET – gastrointestinal permeation enhancing technology, PEG – Polyetholene glycol, POD™ – Protein Oral Delivery, SNAC – salcaprozate sodium, T1D – Type 1 diabetes, T2D – Type 2 diabetes, 5-CNAC - 8-(N-2-hydroxy-5-chloro-benzoyl)-amino-caprylic acid.