Sprifermin

Sprifermin (INN) (developmental code name AS-902330),[1] is a recombinant human fibroblast growth factor 18 (rhFGF18) analog,[2] which is under development by Merck and Nordic Bioscience for the treatment of osteoarthritis.[3] FGF18 and sprifermin are potent agonists of the FGFR2, FGFR3 and FGFR4.[4]

Sprifermin
Clinical data
Other namesAS-902330; rhFGF18; L-Methionyl(human fibroblast growth factor 18 (FGF-18, zFGF5)-(1-169)-peptide)
Identifiers
CAS Number
UNII
Chemical and physical data
FormulaC876H1396N258O256S6
Molar mass19830.71 g·mol−1
3D model (JSmol)
  • CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc4cnc[nH]4)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc6ccc(O)cc6)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc7ccccc7)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc8ccccc8)C(=O)N[C@@H](Cc9ccc(O)cc9)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]%10CSSC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]%11CCCN%11C(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCSC)NC%10=O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc%12ccccc%12)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](Cc%13ccc(O)cc%13)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc%14ccc(O)cc%14)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc%15c[nH]c%16ccccc%15%16)C(=O)N[C@@H](Cc%17ccc(O)cc%17)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](Cc%18ccccc%18)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N%19CCC[C@H]%19C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N%20CCC[C@H]%20C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc%21cnc[nH]%21)C(=O)N[C@@H](Cc%22ccccc%22)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc%23ccc(O)cc%23)C(=O)N%24CCC[C@H]%24C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)N%25CCC[C@H]%25C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)N%26CCC[C@H]%26C(=O)N[C@@H](Cc%27ccccc%27)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc%28ccc(O)cc%28)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)O

In 2020, Merck reported 5-year follow-up data from the Phase 2 clinical trial for knee osteoarthritis, which demonstrated that sprifermin was able to promote statistically significant improvement in cartilage thickness relative to control in a dose-dependent manner, meeting the primary endpoint of the study.[5] Sprifermin was well tolerated with no severe adverse events associated with the treatment.[5] Long-term follow up showed that continual injections, up to 12 per year of bilateral treatment, may need to be sustained over a period of multiple years to prevent recurrence of cartilage loss.[5] Improvement in WOMAC, a secondary endpoint, was met for the Subgroup at Risk.[5]

References
  1. "Inxight Drugs: Sprifermin". National Center for Advancing Translational Sciences.
  2. Gigout A, Guehring H, Froemel D, Meurer A, Ladel C, Reker D, et al. (November 2017). "Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix". Osteoarthritis and Cartilage. 25 (11): 1858–1867. doi:10.1016/j.joca.2017.08.004. PMID 28823647.
  3. "Sprifermin - Merck". Adis Insight. Springer Nature Switzerland AG.
  4. Iwata T, Hevner RF (April 2009). "Fibroblast growth factor signaling in development of the cerebral cortex". Development, Growth & Differentiation. 51 (3): 299–323. doi:10.1111/j.1440-169X.2009.01104.x. PMID 19379279. S2CID 24934958.
  5. Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, et al. (August 2021). "Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study". Annals of the Rheumatic Diseases. 80 (8): 1062–1069. doi:10.1136/annrheumdis-2020-219181. PMC 8292562. PMID 33962962.
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