Lexicon breaks sotagliflozin losing streak with FDA nod in heart failure
Published: May 30, 2023
By Tristan Manalac
The FDA has approved Lexicon Pharmaceuticals’ sotagliflozin, now to be marketed as Inpefa, as a once-daily oral medication to cut the risk of cardiovascular death and heart failure admissions and visits in adult patients with underlying heart failure, the company announced Friday.
Inpefa’s label covers patients across the full range of left ventricular ejection fraction, including those with preserved or reduced ejection fractions. The drug’s indication also allows its use in patients with Type 2 diabetes, chronic kidney disease and other similar underlying cardiovascular risk factors.
Though it doesn’t have a boxed warning, Inpefa’s label bears warnings for side effects including ketoacidosis, intravascular volume depletion, urinary tract infections and hypoglycemia when used concomitantly with insulin.
“Inpefa’s broad label means that we have the ability to compete across the entire spectrum of heart failure patients,” Lexicon CEO Lonnel Coats said in an investor call Tuesday morning.
Still, the company will focus primarily on what Coats calls the “sweet spot of care,” referring to patients who have been stabilized in the hospital and are well enough to be discharged. In line with this setting, Inpefa’s label contains specific instructions on how to dose decompensated patients once they had been stabilized.
“Inpefa will be one of three SGLT inhibitors approved for heart failure, but one of one with clinical data from this unique patient population in its label,” Coats said during the call.
Data from two randomized, double-blinded and placebo-controlled late-stage studies supported the FDA’s regulatory greenlight.
In the Phase III SOLOIST-WHF study, Lexicon evaluated the drug in more than 1,200 patients with Type 2 diabetes who had recently been hospitalized for worsening heart failure. The study demonstrated that Inpefa led to a 33% drop in the composite risk of hospitalization for heart failure, urgent visits for heart failure and cardiovascular death, relative to placebo.
Meanwhile, with more than 10,000 patients enrolled, the Phase III SCORED trial found that Inpefa treatment could reduce the rate of urgent visits, cardiovascular deaths and hospitalizations due to heart failure.
Lexicon expects Inpefa to hit the U.S. market by the end of June 2023, Coates said during the call. The drug will carry a wholesale price tag comparable to existing branded heart failure treatments.
Inpefa’s active ingredient, sotagliflozin, is a dual inhibitor of the SLGT2 and SGLT1 proteins, both of which play a role in glucose absorption in the kidneys and gastrointestinal tract, respectively. This promising mechanism of action attracted industry heavy-hitter Sanofi, which in November 2015 pledged up to $1.7 billion for development and commercialization rights to sotagliflozin.
The partners were initially proposing the dual inhibitor for the treatment of Type 1 diabetes, the New Drug Application (NDA) for which was accepted by the FDA in May 2018.
In January 2019, however, an advisory committee meeting ended in a split vote, with panelists flagging sotagliflozin’s risks such as diabetic ketoacidosis, which could become life-threatening if not managed early. The FDA eventually erred on the side of caution and rejected the NDA in March 2019.
While the partners appealed the FDA’s verdict, Sanofi ended up terminating its contract with Lexicon in September 2019, paying $260 million to leave the partnership. The FDA denied Lexicon’s appeal in December 2019.