sprifermin
{{Short description|Human recombinant FGF18}}
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| CAS_number = 890058-52-3
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| UNII = UEJ4E476ZP
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| C = 876
| H = 1396
| N = 258
| O = 256
| S = 6
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| synonyms = AS-902330; rhFGF18; L-Methionyl(human fibroblast growth factor 18 (FGF-18, zFGF5)-(1-169)-peptide)
}}
Sprifermin (INN; development code AS-902330{{cite web | title = Inxight Drugs: Sprifermin | url = https://drugs.ncats.io/drug/uej4e476zp | work = National Center for Advancing Translational Sciences }}) is a recombinant human fibroblast growth factor 18 (rhFGF18) analog,{{cite journal | vauthors = Gigout A, Guehring H, Froemel D, Meurer A, Ladel C, Reker D, Bay-Jensen AC, Karsdal MA, Lindemann S | display-authors = 6 | title = Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix | journal = Osteoarthritis and Cartilage | volume = 25 | issue = 11 | pages = 1858–1867 | date = November 2017 | pmid = 28823647 | doi = 10.1016/j.joca.2017.08.004 | doi-access = free }} originally developed by Merck, and now being further developed by TrialSpark’s subsidiary, High Line Bio (now Formation Bio), for the treatment of osteoarthritis.{{cite web | url = http://adisinsight.springer.com/drugs/800017598 | title = Sprifermin - Merck | work = Adis Insight | publisher = Springer Nature Switzerland AG }} FGF18 and sprifermin act via the Fibroblast Growth Factor Receptor (FGFR) family, with preferential activity via FGFR3c.{{cite journal | vauthors = Ornitz DM, Itoh N | title = The Fibroblast Growth Factor signaling pathway | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 4 | issue = 3 | pages = 215–266 | date = 2015 | pmid = 25772309 | pmc = 4393358 | doi = 10.1002/wdev.176 }}
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.{{cite journal | vauthors = Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG | display-authors = 6 | title = Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study | journal = Annals of the Rheumatic Diseases | volume = 80 | issue = 8 | pages = 1062–1069 | date = August 2021 | pmid = 33962962 | pmc = 8292562 | doi = 10.1136/annrheumdis-2020-219181 }} 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.{{cite journal | vauthors = Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG | display-authors = 6 | title = Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study | journal = Annals of the Rheumatic Diseases | volume = 80 | issue = 8 | pages = 1062–1069 | date = August 2021 | pmid = 33962962 | pmc = 8292562 | doi = 10.1136/annrheumdis-2020-219181 }} 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. 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. Improvement in WOMAC, a secondary endpoint, was met for the Subgroup at Risk. 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.{{Cite journal | vauthors = Conaghan PG, Katz N, Hunter D, Guermazi A, Hochberg M, Somberg K, Clive J, Johnson M, Goel N | display-authors = 6 |date= June 2023 |title=Pos1348 Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post-Hoc Analysis of the Forward Randomized Trial |url=https://ard.bmj.com/content/82/Suppl_1/1025 |journal=Annals of the Rheumatic Diseases |language=en |volume=82 |issue=Suppl 1 |pages=1025–1026 |doi=10.1136/annrheumdis-2023-eular.2454 |issn=0003-4967|doi-access=free }}
References
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External links
- [http://adisinsight.springer.com/drugs/800017598 Sprifermin - AdisInsight]
{{Growth factor receptor modulators}}