Sprifermin

This article will address the issue of Sprifermin, which has become very relevant in recent times. Sprifermin is a topic that impacts a large number of people in different areas of life, whether professional, personal, social or cultural. Throughout this article, different aspects related to Sprifermin will be explored, from its origin and evolution to its possible future implications. Different perspectives and opinions on the matter will also be analyzed, with the aim of offering a complete and enriching vision of this topic of great interest to today's society.

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

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

  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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