Lexicon shares plunge after FDA AdCom rejects Zynquista again

The US Food and Drug Administration’s (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (AdCom) has once again voted against the approval of Zynquista (sotagliflozin), a medication developed by Lexicon Pharmaceuticals. The recent vote, with a margin of 3-11, was against the use of Zynquista as an additional treatment to insulin therapy for adults with type 1 diabetes (T1D) and chronic kidney disease (CKD). The primary concern cited by the committee was that the benefits of the therapy did not surpass its potential risks.

Following this decision, Lexicon’s stock value plummeted by 38.7% at the market opening on November 1, compared to its closing value on October 30. This drop occurred after trading was halted on October 31 due to the committee’s vote. This is not the first time Zynquista has faced scrutiny; in 2019, an FDA advisory panel split their vote 8-8 on whether the drug's benefits outweighed its risks. Ultimately, the FDA decided not to approve Zynquista at that time.

In the latest AdCom review, Lexicon presented additional data from the SCORED trial, which focused on the type 2 diabetes (T2D)-CKD population, alongside post hoc subgroup analysis from three Tandem studies. Despite these efforts, the committee remained unconvinced of the therapy’s overall benefit-risk profile for the broader T1D and CKD patient population.

Zynquista functions as an oral dual inhibitor of sodium-dependent glucose co-transporter types 1 and 2 (SGLT1 and SGLT2), which are crucial for glucose uptake and reabsorption. In 2019, the European Medicines Agency (EMA) approved Zynquista as an adjunct treatment to insulin for patients with T1D and CKD. Additionally, the FDA has approved the medication, marketed under the name Inpefa, to reduce the risk of cardiovascular death and heart failure in patients with either heart failure or T2D, CKD, and other cardiovascular risk factors.

Lexicon is actively seeking approval for Zynquista in patients with T1D and CKD, specifically targeting those with an estimated glomerular filtration rate (eGFR) of 45 to less than 60, or those with an eGFR greater than 60 and a urine albumin-to-creatinine ratio (uACR) of 30 or more. Despite the committee’s overall rejection, some members acknowledged that Zynquista might be beneficial for a subpopulation of patients with an eGFR of 60 to less than 90 and those with mild to moderate kidney disease. However, the experts called for more data to substantiate Zynquista’s efficacy within this subgroup.

An AdCom is convened at the request of the FDA to review and analyze the safety and efficacy data of a specific therapy. Although the advisory committee’s recommendations are influential, they are not binding. The final decision regarding the approval of a therapy rests solely with the FDA.