A recent Phase 3 randomized, double-blind study published in Seminars in Arthritis and Rheumatism evaluated the efficacy and safety of fasinumab, an investigational nerve growth factor (NGF) inhibitor, in patients with moderate-to-severe osteoarthritis (OA) pain of the knee or hip. The study compared fasinumab with placebo and nonsteroidal anti-inflammatory drugs (NSAIDs) over a 24-week period.
Involving 1,650 patients, the study randomized participants into four groups receiving fasinumab (1 mg every four weeks), diclofenac (75 mg twice daily), celecoxib (200 mg daily), or placebo. By week 24, fasinumab demonstrated superior pain relief and functional improvement compared to placebo. The least-squares mean differences for Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function scores were -0.63 and -0.64, respectively (p = 0.0003). While fasinumab showed numerically greater improvements compared to NSAIDs, the differences in pain reduction did not achieve statistical significance.
Despite its efficacy, safety concerns emerged during the study. Adjudicated arthropathies were reported in 5.6% of patients receiving fasinumab, compared to 1.6% in the placebo group and 1.5% in the NSAID group. However, the incidence of joint replacements remained comparable across groups, with rates of 3.4% in the fasinumab group, 3.6% in the placebo group, and 4.8% in NSAID-treated patients.
Fasinumab, a fully human recombinant IgG4 monoclonal antibody, selectively targets NGF to reduce pain signaling without interfering with other neurotrophins like neurotrophin-3 and brain-derived neurotrophic factor. A separate randomized controlled trial by Tiseo et al., involving 217 OA patients, found that intravenous fasinumab significantly improved walking-induced knee pain and WOMAC scores at 8 and 16 weeks.
Despite its promising results, fasinumab has not received approval from the U.S. Food and Drug Administration (FDA) as of March 2025. Regeneron Pharmaceuticals, in collaboration with Teva Pharmaceuticals, faced developmental setbacks after the FDA imposed a partial clinical hold on a Phase 2b study in 2016 following a case of rapidly progressive osteoarthritis (RPOA). Although Regeneron and Teva reported positive topline Phase 3 results in 2018, subsequent safety evaluations continued to highlight concerns about joint-related adverse events.
In 2021, the FDA’s advisory committee voted 15 to one against the approval of tanezumab, another NGF inhibitor, citing safety risks that outweighed its benefits. Consequently, the FDA rejected tanezumab’s application, and the European Medicines Agency (EMA) also declined approval.
These findings underscore fasinumab’s potential as an effective treatment for OA pain, particularly in patients unresponsive to NSAIDs. However, the increased risk of arthropathy emphasizes the need for careful patient selection and rigorous long-term safety monitoring. Further research may help identify strategies to mitigate these risks and clarify fasinumab’s role in clinical practice.
References
- DiMartino SJ, Gao H, Eng S, Valenzuela G, Fuerst T, Emeremni C et al. Efficacy and safety of fasinumab in an NSAID-controlled study in patients with pain due to osteoarthritis of the knee or hip. BMC Musculoskelet Disord. 2025 Feb 25;26(1):192.
- Dakin P, DiMartino SJ, Gao H, Maloney J, Kivitz AJ, Schnitzer TJ, et al. The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Arthritis Rheumatol. 2019 Nov;71(11):1824-1834.
- Tiseo PJ, Kivitz AJ, Ervin JE, Ren H, Mellis SJ. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebo-controlled exploratory study in osteoarthritis of the knee. Pain. 2014 Jul;155(7):1245-1252.