Lexicon Pharmaceuticals, Inc.

The biotech is preparing to meet with the FDA and start a phase 3 program this year. \n Lexicon Pharmaceuticals is yet again defending a mixed set of data on its non-opioid pain prospect. The biotech focused on low-dose results from its latest phase 2 trial, rather than the overall primary endpoint miss, but investors took a much more downbeat view of the data.Texas-based Lexicon published data from two phase 2 trials in 2022. Based on the findings, the biotech dropped the loading dose from the regimen for its third midphase study to improve tolerability. Monday, Lexicon shared topline results from the third study, which compared three regimens of the AAK1 inhibitor LX9211 to placebo in adults with diabetic peripheral neuropathic (DPN) pain.Pooling data from all the treatment arms, LX9211 was no better than placebo at improving average daily pain score (ADPS) after eight weeks. Lexicon blamed the primary endpoint miss on the high-dose cohort.Mean ADPS fell 1.74 and 1.38 points, respectively, in the low- and high-dose cohorts. People who began on the high dose and then switched to the low dose experienced a 1.7-point reduction. The results look solid compared to Lexicon’s earlier DPN trial, when the biotech saw reductions of 1.4 and 1.3 points, respectively. The problem, for Lexicon, is that placebo performed better in the latest trial too. The mean ADPS reduction on placebo in the latest study was 1.31, compared to 0.7 in the earlier trial. The upshot is the placebo-adjusted change at the low dose fell from around 0.7 to 0.4 between the two trials. Analysts were already questioning whether a 0.7-point delta was meaningful. Steve Edelman, a professor of medicine at the University of California San Diego, made the case that the data point was indeed meaningful at a Lexicon event in January.Investors made their own feelings about this morning\'s results clear, sending Lexicon’s share price down 40% to 42 cents when the markets opened Monday. Lexicon is publicly more positive about the study, which, in its eyes, delivered on its goal of identifying a phase 3 dose. Lexicon has seen separation from the control at the low dose in two trials and a placebo-like dropout rate in the latest study.Buoyed by those findings, the biotech is preparing to meet with the FDA and start a phase 3 program this year. Craig Granowitz, M,D., Ph.D., chief medical officer at Lexicon, made the case that the candidate can hit in phase 3 on a call with analysts to discuss the data, noting that increasing enrollment to the 300 to 350 subjects per arm planned for the phase 3 and extending the study’s duration will bring benefits.“We feel pretty confident that first of all, the trends in pain reduction will continue with the treatment arm, especially with a much lower dropout rate and with many more patients,” Granowitz said. “The variance of the data should also shrink, which should improve the statistical reliability of the dataset.”

Lexicon Pharmaceuticals’ non-opioid drug has failed a mid-stage test in a chronic pain indication — but the company says there’s still a path forward and even potential partnership opportunities for the lower dose. The biotech’s AAK1 inhibitor, dubbed pilavapadin, did not meet the primary endpoint of change from baseline in average daily pain score (ADPS) at eight weeks in the Phase 2b PROGRESS trial in moderate to severe diabetic peripheral neuropathic pain (DPNP). The condition develops when high blood sugar levels damage nerves throughout the body, causing pain and numbness. The primary endpoint miss was driven by a “lack of separation” between the 20 mg dose and placebo, according to a Monday release. The 10 mg pilavapadin dose, meanwhile, demonstrated “early and clinically meaningful separation from placebo” in ADPS, which was maintained throughout the trial, Lexicon said. But the trial technically still failed because its primary endpoint was designed to detect a “dose-response signal” that assumed separation from placebo across all treatment cohorts. Detailed results from PROGRESS will be presented at an upcoming medical meeting. Lexicon’s share price $LXRX plummeted around 29% premarket Monday. The Texas biotech still plans to advance the 10 mg dose into Phase 3 based on PROGRESS as well as a previous mid-stage study called RELIEF-DPN-1. The RELIEF-DPN-1 trial tested 10 mg and 20 mg of pilavapadin given after initial loading doses of 100 mg and 200 mg, respectively. By contrast, the PROGRESS trial did not feature a loading dose. In RELIEF-DPN-1, the 10 mg arm met the ADPS primary endpoint at six weeks versus placebo but the 20 mg arm “narrowly missed statistical significance.” In RELIEF-DPN-1, both treatment arms were also negatively impacted by tolerability issues due to the high-loading doses. But in PROGRESS, the 10 mg dose was well tolerated with most side effects being mild or moderate. “The enormous potential of [pilavapadin] has generated significant interest from potential partners, and we intend to accelerate these discussions while we plan for Phase 3 development,” Lexicon CEO Mike Exton said in the Monday release. He added that the neuropathic pain market represents a “multibillion dollar opportunity.” Pilavapadin took center stage for Lexicon in November when the company got rid of its commercial team and switched tack to focus on clinical development. That decision came on the heels of regulatory setbacks for its type 1 diabetes and chronic kidney disease drug sotagliflozin, which faced two rejections from the FDA in the span of five years. In 2022, pilavapadin failed a Phase 2 study in patients with postherpetic neuralgia, a rare side effect of shingles. Editor’s Note: This article was updated to add information about Lexicon’s share price.

MONDAY, March 3, 2025 -- For patients with type 2 diabetes , chronic kidney disease, and additional cardiovascular risk factors, the dual sodium-glucose co-transporter (SGLT)-1/2 inhibitor sotagliflozin is associated with a significantly reduced rate of major adverse cardiovascular events (MACE), with independent reductions in myocardial infarction and stroke, according to a study published online Feb. 14 in The Lancet Diabetes & Endocrinology . Rahul Aggarwal, M.D., from Harvard Medical School in Boston, and colleagues conducted a prespecified secondary analysis of the SCORED trial, a double-blind, randomized trial enrolling adult patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk factors. A total of 10,584 patients from 750 sites in 44 countries were randomly assigned to receive oral sotagliflozin or placebo (5,292 to each group) between Dec. 8, 2017, and Jan. 20, 2020. The researchers found that the rate of total MACE was significantly lower in the sotagliflozin group versus placebo group (4.8 versus 6.3 events per 100 person-years; hazard ratio [HR], 0.77). Among stratified subgroups, there was a consistent effect for sotagliflozin on total MACE, with no evidence of heterogeneity. Compared with placebo, sotagliflozin also significantly reduced the rate of myocardial infarction (1.8 versus 2.7 events per 100 person-years; HR, 0.68) and stroke (1.2 versus 1.8 events per 100 person-years; HR, 0.66). "This ischemic benefit of sotagliflozin on both stroke and myocardial infarction has not been observed in trials of selective SGLT-2 inhibitors, warranting further investigation of SGLT-1 inhibition as a potential mechanism for these effects," the authors write. Several authors disclosed ties to pharmaceutical companies, including Lexicon Pharmaceuticals, which manufactures sotagliflozin and funded the study.