LX9211 Reduces Diabetic Nerve Pain, Improves Quality of Life in Phase 2 Trial

Rodica Pop-Busui, MD, PhD
Credit: Michigan Medicine

Use of LX9211 was associated with clinically significant benefits for people with diabetic peripheral neuropathic pain, according to results of the phase 2 RELIEF-DPN 1 trial.

Announced by Lexicon Pharmaceuticals on June 19, 2024, results of the study, which examined use of the investigational non-opioid therapy over an 11-week period, support further development of the agent in the phase 2b, dose-ranging PROGRESS trial.^1,2

“Results observed in this study show that LX9211 may become an efficacious treatment for moderate-to-severe pain due to [diabetic peripheral neuropathic pain]. These findings reflect a promising breakthrough in the clinical management of [diabetic peripheral neuropathic pain], one of the strongest risk factors for mortality in people with diabetes, and the leading cause of non-traumatic amputation,” said lead investigator Rodica Pop-Busui, MD, PhD, vice chair of Clinical Research in the Department of Internal Medicine at the University of Michigan.²

A double-blind, multicenter, proof-of-concept trial, RELIEF-DPN 1 was launched with the intent of exploring the safety and efficacy of LX9211 in reducing pain related to diabetic peripheral neuropathy among adults with type 1 or type 2 diabetes. For inclusion in the trial, patients needed to be at least 18 years of age, have type 1 or type 2 diabetes, have an HbA1c of 11% or less, be on stable antihyperglycemic regimen for at least 1 month prior to screening, have confirmed diabetic peripheral neuropathy and chronic neuropathic pain.¹

The trial was designed with 2 parts: a 6-week double-blind treatment period and a 5-week single-blind safety follow-up period. In total, 557 patients underwent screening and were enrolled into a run-in period, with 319 individuals deemed eligible for inclusion and randomized in a 1:1:1 ratio LX9211 10 mg, LX9211 20 mg, or matching placebo once daily. A total of 106, 106, and 107 individuals were assigned to the LX9211 10 mg, LX9211 20 mg, and placebo groups, respectively.¹

The primary outcome of interest for the trial was the change from baseline in average daily pain score, with these differences estimated using mixed models repeated measures analysis. included change from baseline to week 6 in Brief Pain Inventory Short Form for Diabetic Peripheral Neuropathy and Neuropathic Pain Symptom Inventory scores as well as change from baseline in the Patient Global Impression of Change at week 6.¹

Upon analysis, investigators noted statistical significance was achieved for the primary outcome among the low-dose LX9211 group relative to placebo (—1.39 vs —0.72; least squares [LS] mean difference, 20.67 [SE, 0.249]; 95% CI, —1.16 to —0.18; P = .007). However, a numerical improvement that failed to reach statistical significance was observed with the higher dose of LX9211 relative to placebo (—1.27 vs —0.72 points; LS mean difference, —0.55 [SE, 0.254]; 95% CI —1.06 to —0.05; P = .030). Investigators highlighted benefits was observed d improvement in several patient-reported secondary outcomes, including nominally significantly different changes relative to placebo were observed for the low-dose and high-dose LX9211 groups for categories of worst pain (P = .014 and .017 vs placebo, respectively) least pain (P = .015 and .020 vs placebo), and interference of pain with sleep (P = .005 and .002 vs placebo).¹

At the 84th American Diabetes Association Scientific Sessions, an analysis of the trial provided insight into patient perspectives from the trial. Based on a series of interviews with 62 patients from the trial, investigators detail the effects of diabetic peripheral neuropathic pain on quality of life, with results indicating the condition impacted sleep quality in 81%, mood in 66%, and mobility in 66%. Further analysis revealed 37% of patients reported management of diabetic peripheral neuropathic pain was “very difficult”.³

“We are grateful to the investigators, their research teams and the people suffering from [diabetic peripheral neuropathic pain] who participated in this important study,” said Craig Granowitz, MD, PhD, senior vice president and chief medical officer at Lexicon.² “Their contributions have enabled us to commence our large dose-ranging Phase 2b PROGRESS trial, currently enrolling patients throughout the United States.”

References:

1. ^{Pop-Busui R, Patel A, Sang CN, et al. Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study. Diabetes Care. Published online June 19, 2024. doi:10.2337/dc24-0188}
2. ^{Lexicon Pharmaceuticals. Data From Lexicon’s RELIEF-DPN 1 Phase 2 Study of LX9211 Published Today in Diabetes Care, a Peer-Reviewed Journal of the American Diabetes Association. Lexicon Pharmaceuticals. June 19, 2024. Accessed June 23, 2024. https://www.lexpharma.com/media-center/news/2024-06-19-data-from-lexicons-relief-dpn-1-phase-2-study-of-lx9211-published-today-in-diabetes-care-a-peer-reviewed-journal-of-the-american-diabetes-association.}
3. ^{Guadiana LM, Sikirica S, Hardin MB, et al. Patient-Reported Burden of Disease in Diabetic Peripheral Neuropathic Pain—Learnings from In-depth Patient Interviews—Substudy of RELIEF-DPN 1. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.}