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Sprifermin

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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)
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Sprifermin (INN) (developmental code name AS-902330),[1] is a recombinant human fibroblast growth factor 18 (rhFGF18) analog,[2] which is under development by TrialSpark for the treatment of osteoarthritis.[3] FGF18 and sprifermin act via the Fibroblast Growth Factor Receptor (FGFR) family, with preferential activity via FGFR3c.[4]

Osteoarthritis

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In 2020, Merck reported 5-year follow-up data from the Phase 2 clinical trial for knee osteoarthritis (OA). The placebo controlled, multi-center study 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] The findings suggested the ability of FGF18 to arrest progression to joint replacement, with 0% of patients in the high dose group progressing to Total Knee Replacement (TKR) surgery over the 5 year study period; in contrast, nearly 1 in 10 patients of the high risk subgroup progressed to TKR when treated with the placebo.[6] These findings suggest significant potential of FGF18 as a disease modifying drug for the treatment of OA (DMOAD) and warrant further clinical evaluation.

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] Subsequent analysis further demonstrated that a clinically meaningful reduction in the rate of symptomatic progression (WOMAC) was demonstrated in the full trial population and Subgroup at Risk by the high treatment dose.[7]

References

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  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. ^ Ornitz DM, Itoh N (2015). "The Fibroblast Growth Factor signaling pathway". Wiley Interdisciplinary Reviews. Developmental Biology. 4 (3): 215–266. doi:10.1002/wdev.176. PMC 4393358. PMID 25772309.
  5. ^ a b c d 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.
  6. ^ 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.
  7. ^ Conaghan PG, Katz N, Hunter D, Guermazi A, Hochberg M, Somberg K, et al. (June 2023). "Pos1348 Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post-Hoc Analysis of the Forward Randomized Trial". Annals of the Rheumatic Diseases. 82 (Suppl 1): 1025–1026. doi:10.1136/annrheumdis-2023-eular.2454. ISSN 0003-4967.
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