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Background: Currently available therapies for osteoarthritis (OA) are limited in efficacy and duration of response. For intra-articular therapies, steroids provide effective but short-term pain relief, while hyaluronic acid viscosupplements are considered safe, but data on their efficacy varies. MM-II, a novel suspension of large, empty, multilamellar liposomes composed of dimyristoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylcholine (DMPC), coats cartilage, reduces its friction and wear, and decreases degeneration in animal models. In a previously reported first-in-human study, MM-II reduced knee pain for up to 3 months after a single intra-articular (IA) injection in patients with OA. In a phase 2b study evaluating optimal dose, safety, and efficacy of MM-II in patients with symptomatic knee OA, 3 mL of MM-II demonstrated trends in efficacy in terms of the primary endpoint, reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain at W12, and the weekly average of daily knee pain (WADP) visual analogue scale (VAS) scores from W6 through W26. Objectives: To evaluate duration of clinically meaningful pain responses through W26 in patients with symptomatic knee OA after treatment with a single IA injection of 3 mL of MM-II or placebo (PBO). Methods: Patients were enrolled in a 6-arm, randomised, double-blind, PBO-controlled, 26-week trial evaluating a single IA injection of 1, 3, or 6 mL of MM-II or PBO. This analysis focuses on the 3 mL dose, the target dose in future studies. Key inclusion criteria were age ≥40 years, radiographic Kellgren-Lawrence grade 2 or 3 in the index knee, American College of Rheumatology criteria for OA, WOMAC A pain level ≥2/4 within 24 hours of baseline, index knee VAS pain score of ≥50 and ≤90 mm for ≥5/7 days prior to baseline, and intolerance or inadequate response to NSAIDs or acetaminophen. The primary endpoint was change in WOMAC A pain score at W12. Secondary endpoints included WADP scores by VAS at W12, W26, and over time, and WOMAC A pain scores at W26 and over time. We assessed clinical meaningfulness of response from proportions achieving ≥30% and ≥50% pain reduction in WOMAC A and WADP scores for 3 mL MM-II vs PBO across all time points. Safety was assessed by adverse events (AEs). Unless noted, reported P values are nominal and not adjusted for multiplicity. Results: In this analysis, 83 patients received 3 mL of MM-II and 79 received 3 mL of PBO. Among patients treated with 3 mL of MM-II/PBO, 69.9%/64.6% were female; mean ± standard deviation (SD) age and BMI were 64.4 ± 8.4/62.1 ± 8.0 years and 30.5 ± 6.0/30.9 ± 6.4 kg/m2, respectively (all randomized analysis set). Patients who received 3 mL of MM-II vs PBO had early and sustained reductions in WOMAC pain and function subscale scores, with maintenance of benefit through W26 and significance at W16 (P = 0.022) and W20 (P = 0.041). Change from baseline in the WADP score showed a similar profile, starting from W6 and persisting through W26 (Figure 1). Durability of response was demonstrated by percentages of patients with ≥30% and ≥50% improvement in WOMAC A and WADP scores from W4 to W26. More patients treated with 3 mL of MM-II vs PBO experienced ≥30% improvement in WOMAC A score (P = 0.056) and WADP score (P = 0.014) at W26 (Table 1), with trends in reduction of these scores from W8 to W26. The pattern was similar for those achieving ≥50% improvement, with higher responder rates in the 3 mL MM-II vs 3 mL PBO-treated groups and stability through W26. No AEs in MM-II 3–mL-treated patients were severe or led to discontinuation. Conclusion: Currently available IA therapies either provide relatively short-term pain relief or are not convincingly superior to PBO. In contrast, in this study, a single IA injection of 3 mL of MM-II provided both relatively rapid and clinically meaningful pain relief for up to 26 weeks and appeared well tolerated. These data support MM-II as a possible long-lasting treatment for patients with knee OA. REFERENCES: NIL. Acknowledgements: Medical writing and editorial support were provided by Juliette Bouyssou, PhD, of AlphaBioCom, a Red Nucleus company, and funded by Moebius Medical. Disclosure of Interests: Ballari Brahmachari Sun Pharmaceutical Industries Limited, Sun Pharmaceutical Industries Limited, Asger R. Bihlet NBCD A/S, NBCD A/S, Tarini Joshi Sun Pharmaceutical Industries Limited, Mudgal Kothekar Sun Pharmaceutical Industries Limited, Richard C Chou Sun Pharmaceutical Industries, Inc., Roni Wechsler Moebius Medical, Moebius Medical, Sveta Weiner Sun Pharmaceutical Industries, Inc., Siu-Long Yao Sun Pharmaceutical Industries, Inc., Sun Pharmaceutical Industries, Inc., Thomas J. Schnitzer AstraZeneca, Eli Lilly, GSK, Horizon, IBSA Group, Merck, Moebius Medical, Orion, Pfizer, Regeneron, and Xalud, Philip G. Conaghan AbbVie, Eli Lilly, and Novartis, AbbVie, Eli Lilly, Genascense, GSK, Galapagos, Grunenthal, Janssen, Levicept, Merck, Moebius Medical, Novartis, Stryker, Takeda, and TrialSpark.
Brahmachari et al. (Sat,) studied this question.