Published Data in Journal of American Society of Nephrology Highlights Findings on Efficacy and Safety of Sotagliflozin for People With Type 1 Diabetes and Chronic Kidney Disease

Rhea-AI Summary

Lexicon Pharmaceuticals (LXRX) announced the publication of research findings on sotagliflozin in the Journal of American Society of Nephrology. The study analyzed the drug's efficacy and safety when combined with insulin in patients with type 1 diabetes (T1D) and chronic kidney disease (CKD). Key findings show that sotagliflozin achieved similar HbA1c reductions in both CKD and non-CKD patients, with significant placebo-adjusted reductions of -0.4% for 200mg and -0.3% to -0.4% for 400mg doses. The drug demonstrated a lower to neutral risk of severe hypoglycemia and did not significantly increase diabetic ketoacidosis risk. The FDA has set a PDUFA date of December 20, 2024, for Zynquista (sotagliflozin).

Positive

• Significant HbA1c reductions achieved in both CKD and non-CKD patients
• Lower incidence of severe hypoglycemia in CKD patients (4-7% vs 17% placebo)
• FDA PDUFA date set for December 20, 2024, indicating potential near-term approval

Negative

• Small increase in DKA events in CKD patients (3-5% vs 1% placebo)
• No significant effect on systolic blood pressure in CKD subgroup in inTandem1 and 2 trials

Insights

Medical Research Analyst

The publication of sotagliflozin's clinical trial data in JASN represents a significant milestone for Lexicon Pharmaceuticals. The data shows comparable HbA1c reduction in T1D patients with and without CKD, with placebo-adjusted reductions of -0.4% for 200mg and -0.3% for 400mg doses in the CKD subgroup. Notably, the drug demonstrated a favorable safety profile with lower rates of severe hypoglycemia in CKD patients (4-7% vs 17% for placebo) and manageable DKA risk.

With the PDUFA date approaching on December 20, 2024, these peer-reviewed results strengthen sotagliflozin's position for FDA approval. The data is particularly significant as it addresses an unmet medical need in T1D patients with CKD, a population that hasn't seen new treatment options in decades. The positive efficacy and safety profile could support broad adoption if approved, potentially expanding Lexicon's market opportunity in this specialized segment.

People with T1D and CKD treated with sotagliflozin and insulin had similar lowering effects on glycated hemoglobin (HbA1c), the primary endpoint, as people with T1D who do not have CKD

Sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of diabetic ketoacidosis (DKA) among a small number of DKA events

THE WOODLANDS, Texas, Nov. 05, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced the peer-reviewed Journal of American Society of Nephrology (JASN) has published a research paper analyzing the efficacy and safety of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, when added to insulin in patients with type 1 diabetes (T1D) and chronic kidney disease (CKD).

The findings from the study, “Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD,” concluded that people with T1D and CKD treated with sotagliflozin and insulin had similar lowering effects on glycated hemoglobin (HbA1c), the primary endpoint of the underlying clinical trials, as T1D patients who do not have CKD. Further, the findings show that sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of diabetic ketoacidosis (DKA) among a small number of DKA events.

Researchers used data from the 52-week pooled inTandem1 and 2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on HbA1c (primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and DKA, in each case stratified by CKD.

Of the 1,575 patients in the inTandem1 and 2 trials, 237 patients were identified who had CKD. Of the 1,402 patients in the inTandem3 trial, 228 patients were identified who had CKD.

At week 24, significant, placebo-adjusted reductions in HbA1c were observed in inTandem1 and 2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant placebo-adjusted reduction at week 24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1 and 2. At week 52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1 and 2, whereas the incidence of severe hypoglycemia was 5-6% across both sotagliflozin and placebo non-CKD subgroups. The incidence of adjudicated DKA at week 52 in inTandem 1 and 2 was 1%, 5%, and 3%, respectively, for the placebo, 200 mg, and 400 mg doses in the CKD subgroup, compared to 0%, 3%, and 4% in the non-CKD subgroup.

Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups.

“There hasn’t been a new drug approved for patients living with type 1 diabetes and chronic kidney disease in decades,” said study co-author and kidney specialist David Cherney, MD, PhD, University Health Network, University of Toronto. “Previous studies have shown the SGLT inhibitors – including sotagliflozin – lower blood pressure and harmful urinary protein levels to a similar degree in people with type 1 diabetes compared to people with type 2 diabetes. Our current analysis adds important evidence showing that sotagliflozin has the potential to provide benefits for patients with type 1 diabetes and chronic kidney disease, particularly when appropriate steps are taken to reduce the risk of diabetic ketoacidosis.”

“People with T1D and CKD urgently need new treatment options. We believe the findings of this analysis support our position that, if approved by the FDA, sotagliflozin should be included in discussions between clinicians and their patients with T1D and CKD about how to best achieve glycemic control,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer.

As previously reported, the U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) target action date for Zynquista^TM (sotagliflozin) of December 20, 2024.

Click here to read the abstract of the JASN manuscript.

About Sotagliflozin
Discovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients.

About Lexicon Pharmaceuticals
Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains “forward-looking statements,” including statements relating to sotagliflozin and Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

For Investor and Media Inquiries:
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com

FAQ

What were the HbA1c reduction results for sotagliflozin in the LXRX T1D and CKD trials?

The trials showed placebo-adjusted HbA1c reductions of -0.4% for 200mg and -0.3% to -0.4% for 400mg doses in both CKD and non-CKD patients.

When is the FDA PDUFA date for Lexicon's (LXRX) Zynquista?

The FDA has set a PDUFA target action date of December 20, 2024, for Zynquista (sotagliflozin).

What were the hypoglycemia rates for sotagliflozin in LXRX's CKD patient trials?

In CKD patients, severe hypoglycemia rates were 7% for 200mg and 4% for 400mg sotagliflozin, compared to 17% for placebo.