A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Phase 2a Study of the Efficacy and Safety of a Bispecific Fusion Protein (MEDI7352) Targeting NGF and TNFα in Patients with Painful Diabetic Neuropathy

Many patients with painful diabetic neuropathy (PDN) do not achieve meaningful pain relief with standard of care. MEDI7352 is a unique bispecific fusion protein targeting two key mediators of pain, TNF and NGF (at relatively low levels of suppression). We report a randomized, double-blind, placebo-controlled, Phase-2a study (NCT03755934/EudraCT-2018-002523-42) assessing efficacy and safety of MEDI7352 in patients aged [≥]18 years with inadequately controlled PDN. Patients remained on background standard-of-care treatment and were randomized to placebo (n=54) or MEDI7352 intravenously (5g/kg [n=6], 150g/kg [n=16], 450g/kg [n=36]). Primary endpoint was change in pain scores from baseline to Week 12 vs placebo on a numeric rating scale (NRS). Key secondary outcomes included change in pain scores from baseline at visits prior to Week 12 and responder rates. Of 112 patients randomized, 107 received [≥]1 dose study medication; mean age (standard deviation [SD]) in the modified-intent-to-treat population was 60.5 (9.34) years; 62.6% males, 37.4% females. With MEDI7352 450g/kg, change from baseline in pain scores at Week 12 vs placebo was: -1.39 [95% CI: -2.19 to -0.58], p=0.0009; at Week 12, mean (SD) pain scores decreased vs baseline by -2.70 (2.08); 66.7% of patients experienced decreased pain by [≥]30% (p=0.0311 vs. placebo); 42.4% experienced decrease [≥]50% (p=0.0029). MEDI7352 safety was similar to placebo; no adjudicated Rapidly Progressing Osteoarthritis (RPOA) type-1 or RPOA type-2 events were observed in any group. MEDI7352 achieved statistically significant and clinically meaningful pain reduction in patients with PDN vs placebo and provides an opportunity to change the paradigm for challenging-to-treat pain.