1876-LB: Pilavapadin, an Oral, Non-opioid, AAK1 Inhibitor for Diabetic Peripheral Neuropathic Pain (DPNP)—Results from a Phase 2b, Dose-Ranging, Randomized, Multicenter Study

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Introduction and Objective: DPNP is a debilitating diabetes complication affecting ~30% of people with type 1 (T1D) or type 2 (T2D) diabetes. Current therapies offer limited relief with frequent adverse effects highlighting the need for innovative approaches.Methods: PROGRESS was a phase 2b study evaluating the efficacy and safety of pilavapadin (LX9211), a non-opioid inhibitor of adaptor-associated kinase 1 (AAK1), in adults with T1D or T2D and moderate or severe DPNP. Primary outcome was the change in average daily pain score (ADPS) after 8 weeks of once daily placebo (PBO) or one of three pilavapadin doses [10 mg, 20/10 mg (20 mg x 7 days then 10 mg), or 20 mg].Results: 496 participants (mean age 61.5, 41% women, 32% Black, 31% on background DPNP therapies, baseline ADPS 6.9) were randomized. All treatment arms had a significant ADPS improvement from baseline (p<0.001) with numerically greater LS mean (SE) differences from PBO for the 10 mg [-0.42 (0.27)] and 20/10 mg [-0.40 (0.27)] arms. A post hoc analysis excluding the 20 mg arm demonstrated significance (p<0.04) (Figure 1a) with an early separation from PBO which remained throughout the study (Figure 1b). Pilavapadin 10 mg was generally well tolerated. Most common adverse events were nausea and dizziness.Conclusion: These data support the advancement of pilavapadin 10 mg into Phase 3 trials as a promising non-opioid treatment for DPNP.

Disclosure

R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. S. Gopinathan: Employee; Lexicon Pharmaceuticals, Inc. M.B. Hardin: Employee; Lexicon Pharmaceuticals, Inc. C.B. Granowitz: None. P.L. Banks: None. P. Pierce: Employee; Lexicon Pharmaceuticals, Inc. M. Girard: None. G. Umpierrez: Research Support; Abbott, Dexcom, Inc., Bayer Pharmaceuticals, Inc, Corcept Therapeutics. Advisory Panel; Dexcom, Inc., GlyCare Health.

Funding

Lexicon Pharmaceuticals



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