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. 2024 Oct 22;6(4):100533.
doi: 10.1016/j.ocarto.2024.100533. eCollection 2024 Dec.

A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip

Stephen J DiMartino  1 , Jingning Mei  1 , Thomas J Schnitzer  2 , Haitao Gao  1 , Simon Eng  1 , Christine Winslow  1 , Tina Ho  1 , Kenneth C Turner  1 , Hazem E Hassan  1 , Yamini Patel  1 , John D Davis  1 , Ngan Trinh  1 , Angela Manley  1 , Garen Manvelian  1 , Michael Fetell  3 , Ned Braunstein  1 , Gregory P Geba  1 , Paula Dakin  1
Affiliations

A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip

Stephen J DiMartino et al. Osteoarthr Cartil Open. .

Abstract

Background: Pain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain.

Methods: In this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 ​mg every 4 weeks [Q4W] and 1 and 6 ​mg every 8 weeks [Q8W] for 52 weeks). Primary safety endpoints included adverse events, adjudicated arthropathies (AAs), and joint replacements (JRs). Co-primary endpoints of an efficacy sub-study were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores. During the study, higher fasinumab doses were discontinued for safety; 1 ​mg doses continued.

Results: Of 13,945 patients screened, 5331 were randomized; 1074 were included in the efficacy sub-study. AAs and JRs occurred in all groups. Increased severity of disease at baseline was associated with higher rates of AAs and JRs. A dose-dependent risk of AA or JR was observed for fasinumab; in the 1 ​mg groups, only a small percentage of patients with JR had prior AA. Fasinumab significantly improved WOMAC pain and physical function scores compared with placebo; least squares mean differences versus placebo were -1.22 and ​-1.20 for 1 ​mg Q4W and -0.73 and ​-0.74 for 1 ​mg Q8W, respectively (P<0.001).

Conclusion: AAs and JRs showed a dose relationship to fasinumab and were associated with baseline OA status. Fasinumab achieved statistically significant improvements in WOMAC pain and physical function scores compared with placebo.

Keywords: Fasinumab; Osteoarthritis; Pain; Safety.

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Conflict of interest statement

JM, SE, CW, TH, KCT, HEH, YP, NT, AM, GM, and NB are all employees of and shareholders in Regeneron Pharmaceuticals, Inc. SJD, HG, GPG, and PD are all employees of and shareholders in Regeneron Pharmaceuticals, Inc., who report having three patents pending with Regeneron Pharmaceuticals, Inc. TJS reports grants/contracts paid to his institution by 10.13039/100009857Regeneron Pharmaceuticals, Inc., 10.13039/100004319Pfizer Inc., 10.13039/100004312Eli Lilly and Company, 10.13039/100002429Amgen Inc., Grünenthal, 10.13039/100019832Galapagos NV, 10.13039/100004336Novartis AG, Techfields Inc., Paradigm Pharmaceuticals Inc., Kolon TissueGene, Inc., 10.13039/100014927Anika Therapeutics, and Taiwan Liposome Company, Ltd.; consulting fees paid to him by 10.13039/100004319Pfizer Inc., 10.13039/100004312Eli Lilly and Company, IBSA Pharma Inc., 10.13039/100004330GlaxoSmithKline Pharmaceuticals, Biosplice Therapeutics, Collegium Pharmaceutical, Xalud Therapeutics, Grünenthal, Techfields Inc., 10.13039/100019832Galapagos NV, Unity Biotechnology, Paradigm Pharmaceuticals Inc., 10.13039/100004325AstraZeneca, 10.13039/100004330GlaxoSmithKline Pharmaceuticals, Genascense, Tremeau Pharmaceuticals, Inc., Moebius Medical; and participating in and receiving payment for a data safety monitoring board or advisory board by IQVIA, 10.13039/100004325AstraZeneca, Alira Health, and Horizon Therapeutics. JDD is an employee of and shareholder in Regeneron Pharmaceuticals, Inc., who reports having two patents pending with Regeneron Pharmaceuticals, Inc. MF is an employee of and shareholder in Teva Pharmaceutical Industries Ltd. and reports having received payment from Teva Pharmaceutical Industries Ltd. for travel and attendance at investigator meetings.

Figures

Fig. 1
Fig. 1
Study flow diagram. EOS, end of study; EOT, end of treatment.
Fig. 2
Fig. 2
Patient disposition for the combined data across the three cohorts. Patients were enrolled into three consecutive cohorts: high-dose safety (n ​= ​2491), efficacy sub-study (n ​= ​1074), and 1 ​mg safety (n ​= ​1766). FAS-LTS, full analysis set for the long-term safety study; Q4W, every 4 weeks; Q8W, every 8 weeks; Tx, treatment.
Fig. 3
Fig. 3
Percentages of patients with (a) AAs, (b) DAs, and (c) JRs by number of joints with OA at baseline (SAF-LTS). AA, adjudicated arthropathy; DA, destructive arthropathy; JR, joint replacement; OA, osteoarthritis; Q4W, every 4 weeks; Q8W, every 8 weeks; SAF-LTS, safety analysis set for long-term safety study.
Fig. 4
Fig. 4
(a) Percentage of patients achieving various levels of pain relief as measured by WOMAC pain subscale score, and (b) change from baseline in average weekly walking index joint pain score using 0–10 NRS pain scale (FAS-sub-study). P values are nominal for the fasinumab 3 ​mg and fasinumab 6 ​mg doses at 30 ​% improvement and for all fasinumab doses at 50 ​% and 70 ​% improvement. FAS-sub-study, full analysis set for efficacy sub-study; NRS, numerical rating scale; Q4W, every 4 weeks; Q8W, every 8 weeks; SC, subcutaneous; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.
See this image and copyright information in PMC

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