Objective:

To present PROGRESS efficacy supporting selection of pilavapadin 10 mg as the optimal dose for Phase 3 in diabetic peripheral neuropathic pain (DPNP).

Background:

DPNP remains a challenging neuropathic pain condition with many patients failing to achieve adequate pain control, and additional analgesic options are often needed. Current therapies offer limited relief highlighting the need for innovative treatment alternatives. Pilavapadin is a novel, non-opioid, investigational drug with a differentiated mechanism of action for pain reduction in DPNP.

Design/Methods:

Adults with DPNP received pilavapadin 10 mg or placebo once daily for 8 weeks. Pain outcomes were assessed using the Brief Pain Inventory–Diabetic Peripheral Neuropathy (BPI-DPN). Efficacy was evaluated with a mixed-model repeated-measures analysis of change from baseline to Week 8. The outcomes reported here are: Average Pain (BPI-DPN Q5), Worst Daily Pain (BPI-DPN Q3), and Least Daily Pain (BPI-DPN Q4).

Results:

At Week 8, pilavapadin 10 mg reduced BPI-DPN Average Pain (Q5) more than placebo (LS mean change −1.52 [SE 0.191] vs −0.91 [0.193]; p=0.022). For Worst Daily Pain (Q3), changes favored pilavapadin (−1.69 [0.205] vs −1.17 [0.207]; p=0.071). For Least Daily Pain (Q4), changes also favored pilavapadin (−1.23 [0.213] vs −0.79 [0.216]; p=0.133). Treatment emergent adverse events (TEAEs) leading to discontinuation occurred in 9/122 (7.4%) with pilavapdin 10 mg vs 2/123 (1.6%) with placebo; the most common with pilavapadin were nausea (4/122, 3.3%), dizziness (3/122, 2.5%), and headache (1/122, 0.8%). Overall study completion in the 10-mg arm was similar to placebo.

Conclusions:

Pilavapadin 10 mg achieved a nominally significant reduction in Average Pain at Week 8 versus placebo, with concordant improvements in Worst and Least Daily Pain. The 10-mg dose was generally well tolerated over 8 weeks, with completion rates comparable to placebo and few discontinuations due to TEAEs. These findings support advancing pilavapadin 10 mg to Phase 3 evaluation in DPNP.