Hormones
and Growth factors

• Darbe­po­etin alfa
• Epoetin alfa
• FSH
• G‑CSF
• HGH
• Insulin
• Inter­feron-β1a
• pegG-CSF
• PTH

Darbe­po­etin alfa

Darbe­po­etin alfa (Aranesp®) contains in compar­ison to natural erythro­poi­etin five amino acid changes (at N30, T32, V87, N88, T90) resulting into creation of two new sites for N‑linked carbo­hy­drate addi­tion. It has a three-fold longer serum half-life as compared to epoetin alpha and epoetin beta. Darbe­po­etin alfa stim­u­lates erythro­poiesis by the same mech­a­nism as endoge­nous erythro­poi­etin. Aranesp® is indi­cated for the treat­ment of anemia due to chronic kidney disease, including patients on dial­ysis and patients not on dial­ysis. Aranesp® is also indi­cated for the treat­ment of anemia in patients with non-myeloid malig­nan­cies where anemia is due to the effect of concomi­tant myelo-suppres­sive chemotherapy. Patents on Aranesp® will expire in US in May 2024 and already expired in Europe in July 2016. Learn more

Epoetin alfa

Epoetin alfa (Epogen® / Eprex® / Procrit®) contains 165 amino acids with the iden­tical sequence of natu­rally occur­ring erythro­poi­etin. Epoetin alfa and epoetin beta have differ­ences in the glyco­sy­la­tion pattern. The mode of action of epoetin alpha is the same as of that of darbe­po­etin alpha. Epogen® is indi­cated for the treat­ment of anemia due to chronic kidney disease, anemia due to zidovu­dine in patients with HIV infec­tion, treat­ment of patients with non-myeloid malig­nan­cies, and for reduc­tion of the need for allo­geneic red blood cell trans­fu­sions during elec­tive, noncar­diac, nonva­s­cular surgery. The patents on Epogen® / Eprex® expired in US and Europe in 2013. Learn more

FSH

Follicle stim­u­lating hormone (FSH) consists of two non-cova­lently linked glyco­pro­teins desig­nated as alpha- and beta-subunits, which consist of 92 and 111 amino acids, respec­tively. The mole­c­ular weight is 22.7 kDa. Follitropin is the corre­sponding recom­bi­nantly produced mole­cule and is marketed as follitropin alpha (Gonal F®) and follitropin beta (Puregon®). The amino acid sequences of follitropin alpha and beta are iden­tical to that of FSH, and there are only differ­ences in glyco­sy­la­tion patterns. FSH is synthe­sized and secreted by the gonadotrophs of the ante­rior pitu­itary gland. In general, it regu­lates the devel­op­ment, growth, pubertal matu­ra­tion, and repro­duc­tive processes of the body including matu­ra­tion of ovarian folli­cles and sperm cells. Follitropin is indi­cated for different compli­ca­tions in ovula­tion and preg­nancy. Basic patents have already been expired. Learn more

G‑CSF

Filgrastim (gran­u­lo­cyte colony stim­u­lating factor, G‑CSF, Neupogen®) consists of 175 amino acid residues (18.8 kDa) with two disul­fide bridges. Filgrastim binds to the G‑CSF receptor, stim­u­lates the prolif­er­a­tion of prog­en­itor cells and their matu­ra­tion into neutrophils (white blood cells). Filgrastim also stim­u­lates the release of neutrophils from bone marrow and increases their phago­cytic activity. By stim­u­la­tion of the produc­tion of more neutrophils, filgrastim treat­ment can thus be used to fight infec­tion in patients under­going chemotherapy for cancer treat­ment. Neupogen® is approved for five indi­ca­tions in the following patient popu­la­tions: Chemotherapy ‑induced febrile neutropenia, acute myeloid leukemia, cancer patients receiving bone marrow trans­plant, periph­eral blood prog­en­itor cell collec­tion and engraft­ment, and severe chronic neutropenia. Patents on Neupogen® expired in the US in December 2013 and in Europe in 2006. Learn more

HGH

Human growth hormone (HGH, Nutropin®, Huma­t­rope®, Genotropin®, Norditropin®, Saizen®), also known as soma­totropin, is a 191-amino acid, single-chain, non-glyco­sy­lated polypep­tide that is synthe­sized and secreted by soma­totropic cells within the lateral wings of the ante­rior pitu­itary gland. It is anabolic and stim­u­lates growth, cell repro­duc­tion, and cell regen­er­a­tion. HGH is indi­cated as replace­ment therapy in persons with growth hormone defi­ciency. There is off-label prescrip­tion and use of HGH for a variety of other appli­ca­tions. Human pitu­itary-derived hormone was avail­able since the late 1950s and in 1981. Genetech devel­oped the first recom­bi­nant product. Patents already expired and a variety of biosim­i­lars are marketed or in devel­op­ment. Learn more

Insulin

Animal sourced insulins are now rarely avail­able in devel­oped coun­tries and even use of recom­bi­nant human insulin is declining in different markets whereas insulin analogues are domi­nating the market since years. Basal insulins are long acting, bolus insulins are fast acting. Insulin is indi­cated to treat high blood glucose including diabetes mellitus type 1 and 2, gesta­tional diabetes, and compli­ca­tions of diabetes such as diabetic ketoaci­dosis and hyper­os­molar hyper­glycemic states. Insulin is also used with glucose to treat high blood potas­sium levels. Patent protec­tion of recom­bi­nant human insulin has expired for more than 15 years and also patents for many analogues have been expired so far, e.g. for Lantus® and Humalog®. Learn more

Inter­feron-β1a

Inter­feron-β1a (IFN-β1a, Avonex®) is a cytokine of the inter­feron family. It is a 166 amino acid glyco­pro­tein with a single N‑linked carbo­hy­drate chain on Asn80 residue. Commer­cial IFN-β1a prepa­ra­tions have core-fuco­sy­lated glyco­forms differing in sialy­la­tion and glycol-anten­nary degree. IFN-β1a is acting on a variety of processes and mole­cules within the immune system. For example, it balances the expres­sion of anti-inflam­ma­tory and pro-inflam­ma­tory cytokines. Avonex® is indi­cated for treat­ment of relapsing forms of multiple scle­rosis to slow accu­mu­la­tion of phys­ical disability and to decrease frequency of clin­ical exac­er­ba­tions in patients with first clin­ical episode and magnetic reso­nance imaging consis­tent with multiple scle­rosis. Basic patents for Avonex® have expired in 2013. Learn more

pegG-CSF

Pegfil­grastim (pegy­lated gran­u­lo­cyte colony stim­u­lating factor, pegG-CSF, Neulasta®) is a variant of G‑CSF coupled to a poly­eth­ylene glycol (PEG) moiety at the N‑terminus of human G‑CSF. This pegy­lated form has a longer half-life, thus reducing the neces­sity of daily injec­tions. The patents on Neulasta® expired in US in October 2015 and in Europe in August 2017. Learn more

PTH

Parathy­roid hormone (PTH, Natpara®, Preos™, Preo­tact®) is a polypep­tide containing 84 amino acids (9.4 kDa). Only the 34 N‑terminal amino acids are required for the bioac­tive confor­ma­tion. Teri­paratide (Forteo®) consisting of these 34 amino acids has the same effi­cacy as PTH. PTH secreted by chief cells of the parathy­roid glands is the primary regu­lator of calcium and phos­phate metab­o­lism in bone and kidney. It is acting upon the PTH‑1 receptor in bone and kidney, and the PTH‑2 receptor in the central nervous system, pancreas, testis, and placenta. PTH increases serum calcium levels. Thus, chron­i­cally elevated PTH will deplete bone stores. Teri­paratide is indi­cated for treat­ment of osteo­porosis in post­menopausal women and men at high risk for frac­ture and for gluco­cor­ti­coid-induced osteo­porosis in men and post­menopausal women. PTH is indi­cated as an adjunct to calcium and vitamin D to control hypocal­cemia in patients with hypoparathy­roidism. The patents of Forteo® expired in US and Europe in August 2019. Learn more