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Background:Tanezumab is a monoclonal antibody directed against nerve growth factor. It is in development for the treatment of moderate to severe chronic pain associated with osteoarthritis (OA) in adult patients for whom other treatments are ineffective or not appropriate. Phase 3 clinical trials have demonstrated the efficacy of subcutaneous tanezumab versus placebo for pain and function outcomes over various timepoints. Largely similar change from baseline was demonstrated in an oral nonsteroidal anti-inflammatory drug (NSAID)-controlled study.1,2,3,4 The efficacy of some other OA therapies can be dampened in patients with depression, anxiety, or insomnia.5,6,7Objectives:A post-hoc analysis to explore the efficacy of subcutaneous tanezumab after 16 weeks treatment, as compared to oral NSAID, in patients with OA and a history of depression, anxiety, or insomnia at baseline.Methods:Subgroup analysis of data from a randomized, double-blind, double-dummy, active-controlled phase 3 study of subcutaneous tanezumab (2.5 mg or 5 mg every 8 weeks) vs twice daily oral NSAID in patients (≥18 years) with radiographically-confirmed moderate to severe hip or knee OA (Kellgren-Lawrence grade ≥2; NCT02528188).4 Co-primary efficacy endpoints were change from baseline to week 16 in Western Ontario and McMaster Universities OA Index (WOMAC*) Pain and Physical Function subscale scores (both ≥5/10 at randomisation; increasing score indicates increasing pain/disability), and Patient’s Global Assessment of OA (PGA-OA, ≥3/5 at randomisation; increasing score indicates poorer condition). Enrolled patients had a history of inadequate pain relief with acetaminophen; inadequate pain relief with/intolerance to/contraindication to tramadol or opioids; or an unwillingness to take opioids. Patients were on a stable dose of NSAID for ≥30 days before screening. Data are presented as least squares (LS) mean change from baseline to week 16 for the whole population and for subgroups of patients with/without a history of depression, anxiety, or insomnia at baseline. Exploratory statistical analysis was conducted by analysis of covariance. P values were not adjusted for multiplicity. This exploratory post-hoc analysis was not part of the pre-specified hypothesis testing plan or included in any sample size calculations; therefore, comparisons between treatment arms or patient subgroups should be interpreted with caution.Results:Overall, 2996 patients were randomized and received at least one dose of study treatment (subcutaneous tanezumab 2.5 mg: n=1002; subcutaneous tanezumab 5 mg: n=998; oral NSAID: n=996). In this population (comprising patients with or without a history of anxiety, depression or insomnia), all treatments were associated with notable and largely similar magnitude improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA at week 16 (Figure 1). Across treatment groups, differences in LS mean change from baseline in patients with and without a history of depression, anxiety or insomnia ranged between 0 - 0.34 for WOMAC Pain and Physical Function and 0 - 0.19 for PGA-OA.Conclusion:Patients with a history of depression, anxiety, or insomnia did not appear to experience dampened improvements in pain or function with tanezumab or NSAID, as compared to those without.References:[1]Schnitzer T, et al. JAMA. 2019;322(1):37-48;[2]Berenbaum F, et al. Ann Rheum Dis. 2020;79(6):800-10;[3]Schnitzer T, et al. Semin Arthritis Rheum. 2020;50(3):387-93;[4]Hochberg M, et al. Arthritis Rheumatol. In Press;[5]Sharma A, et al. Open Access Rheumatol. 2016;31(8):103-13;[6]Mallen C, et al. PLoS Med. 2017;14(4):e1002273;[7]Campbell C, et al. Arthritis Care Res. 2015;67(10):1387-96.Acknowledgements:Study sponsored by Pfizer and Eli Lilly and Company. Editorial support was provided by Jennifer Bodkin of Engage Scientific Solutions and funded by Pfizer and Eli Lilly and Company.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sun, UCB, Theresa Mallick-Searle Speakers bureau: Allergan, Abbvie, Eli Lilly and Company, Salix, Consultant of: Pfizer, Eli Lilly and Company, Elizabeth Johnston Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Dominique Menuet Employee of: Pfizer, Ruoyong Yang Employee of: Pfizer, Robert J Fountaine Shareholder of: Pfizer, Employee of: Pfizer.

Background LASO, a next generation selective estrogen receptor modulator (SERM), is in late development for the treatment of osteoporosis. It is oxidatively and conjugatively metabolized. Since ethnic differences in drug metabolism exist, potential PK/PD differences for LASO in J and C PM women were explored. Methods Two randomized, investigator blind, parallel-group studies were run in PM women. The study in J subjects was placebo-controlled, whereas the study in C subjects was not. Daily 0.25, 0.5 mg or placebo tablets were given for 14 days, with loading doses of 8-times the daily dose given on day 1. Nine subjects were treated at each active dose level, with six J subjects treated with placebo. Plasma/serum samples were collected during and following treatment for PK/PD evaluations. Results The PK/PD of LASO were similar in J and C subjects. Exposure increased predictably with dose, with a mean T1/2 of approximately 150 hours. LDL concentrations generally decreased with LASO treatment, whereas HDL was not consistently affected. LASO was well-tolerated. Conclusions Following daily dosing for 14 days, there do not appear to be significant differences in LASO PK/PD/safety between J and C populations at clinically relevant doses. Clinical Pharmacology & Therapeutics (2005) 77, P83–P83; doi: 10.1016/j.clpt.2004.12.209