Chemistry:Sprifermin
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| Other names | AS-902330; rhFGF18; L-Methionyl(human fibroblast growth factor 18 (FGF-18, zFGF5)-(1-169)-peptide) |
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| Chemical and physical data | |
| Formula | C876H1396N258O256S6 |
| Molar mass | 19830.71 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
- ↑ "Inxight Drugs: Sprifermin". National Center for Advancing Translational Sciences. https://drugs.ncats.io/drug/uej4e476zp.
- ↑ "Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix". Osteoarthritis and Cartilage 25 (11): 1858–1867. November 2017. doi:10.1016/j.joca.2017.08.004. PMID 28823647.
- ↑ "Sprifermin - Merck". Adis Insight. Springer Nature Switzerland AG. http://adisinsight.springer.com/drugs/800017598.
- ↑ "The Fibroblast Growth Factor signaling pathway". Wiley Interdisciplinary Reviews. Developmental Biology 4 (3): 215–266. 2015. doi:10.1002/wdev.176. PMID 25772309.
- ↑ 5.0 5.1 5.2 5.3 "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. August 2021. doi:10.1136/annrheumdis-2020-219181. PMID 33962962.
- ↑ "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. August 2021. doi:10.1136/annrheumdis-2020-219181. PMID 33962962.
- ↑ "Pos1348 Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post-Hoc Analysis of the Forward Randomized Trial" (in en). Annals of the Rheumatic Diseases 82 (Suppl 1): 1025–1026. June 2023. doi:10.1136/annrheumdis-2023-eular.2454. ISSN 0003-4967. https://ard.bmj.com/content/82/Suppl_1/1025.
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