The FDA's Endocrinologic and Metabolic Drugs Advisory Committee (AdCom) has voted against the approval of Lexicon Pharmaceuticals' Zynquista (sotagliflozin) as an add-on treatment to insulin for managing blood glucose levels in adults with type 1 diabetes (T1D) and chronic kidney disease (CKD). The committee voted 3-11 against the approval, citing concerns that the therapy's benefits do not outweigh its risks.
Impact on Lexicon Pharmaceuticals
Following the AdCom vote, Lexicon's stock experienced a significant drop, declining by 38.7% at market open on November 1st. This decline reflects the market's response to the uncertain future of Zynquista as a treatment option for this patient population.
Previous Review and Current Application
This is not the first time Zynquista has faced scrutiny from the FDA. In 2019, an AdCom was convened to evaluate the drug's efficacy, resulting in a split vote (8-8) regarding its benefit-risk profile. The FDA ultimately declined to approve Zynquista at that time. For the current review, Lexicon provided additional data from the SCORED trial (NCT03315143) focusing on a matched type 2 diabetes (T2D)-CKD population, along with post-hoc subgroup analyses from the three Tandem studies.
Lexicon was seeking approval for Zynquista in T1D patients with CKD who had an estimated glomerular filtration rate (eGFR) of 45 to less than 60 or an eGFR of greater than 60 with a urine albumin-to-creatinine ratio (uACR) of 30 or greater.
Zynquista's Mechanism and Existing Approvals
Zynquista functions as an oral dual inhibitor of sodium-dependent glucose co-transporter types 1 and 2 (SGLT1 and SGLT2), which are involved in glucose uptake and reabsorption. While the FDA has not approved Zynquista for T1D and CKD, it is approved for reducing the risk of cardiovascular death and heart failure in patients with either heart failure or T2D, CKD, and other cardiovascular risk factors, where it is marketed as Inpefa. The European Medicines Agency (EMA) approved the therapy in 2019 as an adjunct treatment to insulin in T1D and CKD.
Committee Concerns and Future Prospects
While the AdCom was largely unconvinced of Zynquista's efficacy in the proposed population, some members suggested that the therapy's benefits might outweigh its risks in a subpopulation of patients with an eGFR of 60 to less than 90 and those with mild to moderate kidney disease. However, these experts emphasized the need for more data to confirm Zynquista's efficacy in this specific subgroup.
It is important to note that the AdCom's recommendations are non-binding, and the final decision rests with the FDA. However, the negative vote significantly impacts the likelihood of Zynquista's approval for T1D and CKD, potentially limiting its market reach.
