Lexicon plans new bid for Zynquista in type 1 diabetes

Lexicon Pharmaceuticals has reaffirmed its commitment to seeking regulatory approval for its drug Zynquista (sotagliflozin) as an adjunct treatment for type 1 diabetes (T1D) and chronic kidney disease (CKD). Zynquista is an oral medication that inhibits the sodium-dependent glucose co-transporters types 1 and 2 (SGLT1 and SGLT2), which are involved in glucose uptake and reabsorption. Lexicon plans to resubmit the new drug application (NDA) to the Food and Drug Administration (FDA) by mid-2024, following feedback from the agency.

The journey of Zynquista has been marked by significant challenges. In 2019, the FDA declined to approve the therapy due to safety concerns, following a split 8-8 vote from its advisory committee. The primary concern was the risk of diabetic ketoacidosis, a severe and potentially life-threatening complication that requires urgent treatment. This rejection led Sanofi to withdraw from its licensing agreement for Zynquista.

Despite these setbacks, Lexicon managed to secure approval for Zynquista from the European Medicine Agency (EMA) in 2019 as an adjunctive treatment to insulin for T1D and CKD. However, this authorization was later withdrawn in 2022 by the holders of Zynquista’s marketing rights in Europe, Guidehouse Germany. The company cited commercial reasons for not continuing to market the product in the European Union.

Zynquista has shown promise in various therapeutic areas. It has been approved by the FDA to reduce the risk of cardiovascular death and heart failure and is also approved for use in patients with type 2 diabetes, CKD, and other cardiovascular risk factors. The drug is marketed under the name Inpefa for its cardiovascular disease indication.

Lexicon Pharmaceuticals is not stopping there. The company is also exploring the use of sotagliflozin as a treatment for hypertrophic cardiomyopathy, with a Phase III clinical trial set to commence in mid-2024. As of March 31, 2023, Lexicon reported having $355.6 million in cash reserves, indicating a robust financial position to support its ongoing and future projects.

If approved, Zynquista will enter a competitive market, facing rival SGLT-2 inhibitors such as AstraZeneca’s Farxiga (dapagliflozin), Boehringer Ingelheim’s Jardiance (empagliflozin), and Johnson & Johnson’s Invokana (canagliflozin). Additionally, it will compete with innovative therapies like islet cell transplantation. Notably, in June 2023, the FDA approved the first-ever islet cell therapy for T1D, CellTrans’ Lantidra (donislecel).

Lexicon’s pipeline includes other promising treatments. LX9211 is a non-opioid therapy for diabetic peripheral neuropathic pain, currently being evaluated in a Phase II PROGRESS trial, with topline data expected in the second quarter of 2025. Another candidate, LX9851, is being developed for obesity and weight management.

In summary, Lexicon Pharmaceuticals is steadfast in its efforts to obtain FDA approval for Zynquista for T1D and CKD. The company is also advancing its research in other therapeutic areas, supported by a strong financial foundation and a diverse drug development pipeline.