The Food and Drug Administration has determined that data collected on the dual SGLT1/2 inhibitor sotagliflozin (Zynquista) for treating patients with type 2 diabetes in the SOLOIST and SCORED pivotal trials can help support a New Drug Application (NDA) submission, according to a statement released on Jan. 14 by Lexicon Pharmaceuticals, the company developing this drug. Lexicon concurrently said that it hopes to potentially file this NDA later in 2021.
The statement said the FDA’s decision related to an NDA for “an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.”
Results from SOLOIST and SCORED, first reported in November 2020 at the American Heart Association scientific sessions, showed statistically significant benefits for their respective primary endpoints.
The findings also demonstrated several novel benefits from the first advanced clinical trials of an SGLT inhibitor that blocks both the SGLT2 protein in kidneys as well as the SGLT1 protein, which resides primarily in the gastrointestinal system and is the main route for glucose out of the gut.
In both SOLOIST and SCORED, patient outcomes on sotagliflozin tracked the benefits and adverse effects previously seen with several SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), but in addition showed several unprecedented benefits: An ability to lower hemoglobin A1c in patients with severely depressed renal function, safe initiation in patients recently hospitalized for heart failure, the first prospective data to show improvements in patients with heart failure with preserved ejection fraction, and a higher level of protection against MIs and strokes than the SGLT2 inhibitors.
The FDA’s willingness to consider data from both trials in an NDA was not a given, as the primary endpoints for both trials underwent tweaking while they were underway to compensate for an unexpectedly early end to patient enrollment and follow-up caused by changes in drug company sponsorship and challenges introduced by the COVID-19 pandemic.
In 2019, the FDA denied the NDA for sotagliflozin as a treatment for patients with type 1 diabetes, but this indication received approval in Europe.
SOLOIST and SCORED were sponsored initially by Sanofi, and more recently by Lexicon.