Heart Failure Treatment Breakthrough: INPEFA Receives FDA Green Light with Comprehensive Label Coverage

New SGLT inhibitor demonstrates 33% risk reduction in cardiovascular events across all ejection fraction types

The U.S. FDA has cleared INPEFA™ (sotagliflozin), marking a significant advancement in heart failure management. The approval encompasses a notably broad therapeutic scope—treating patients across the entire spectrum of left ventricular ejection fraction conditions, regardless of diabetes status.

Clinical Evidence Behind the Approval

INPEFA’s regulatory clearance rests on compelling outcomes from the SOLOIST-WHF trial, one of two major Phase 3 studies involving approximately 12,000 patients. The data revealed that sotagliflozin reduced the combined risk of cardiovascular death, heart failure hospitalization, and urgent heart failure visits by 33% compared to placebo. This benefit proved particularly relevant for recently hospitalized patients experiencing acute decompensation—the highest-risk population for readmission within 30 days post-discharge.

The parallel SCORED study further expanded the evidence base, demonstrating efficacy in patients with type 2 diabetes and chronic kidney disease who face elevated cardiovascular risk.

Expanded Treatment Scope

Unlike earlier SGLT inhibitor approvals, INPEFA’s label covers both preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) presentations. This breadth aligns with 2022 guidance from the American Heart Association, American College of Cardiology, and Heart Failure Society of America recommending SGLT inhibitor therapy as first-line treatment. An April 2023 ACC expert consensus statement further emphasized SGLT2 inhibitor benefits for HFpEF patients achieving hemodynamic stability.

Mechanism and Patient Population

Sotagliflozin functions as a dual inhibitor of sodium-glucose cotransporters types 2 and 1 (SGLT2 and SGLT1). SGLT2 operates in renal tubules managing glucose reabsorption, while SGLT1 functions in gastrointestinal glucose absorption. This dual mechanism distinguishes INPEFA within its pharmacological class.

The drug addresses a substantial unmet need: approximately 6.7 million Americans currently live with heart failure, with projections rising to 8.0 million by 2030. Heart failure drives the majority of hospitalizations in patients aged 65 and older, accounting for roughly 1.3 million annual admissions. The 30-day post-discharge window presents critical vulnerability, with 7% mortality and 25% rehospitalization rates.

Safety Profile and Monitoring Requirements

INPEFA requires careful patient stratification and monitoring. Healthcare providers must assess renal function and volume status prior to initiation and correct any existing depletion. Dosing adjustments may commence during hospitalization or immediately upon discharge once hemodynamic stability is achieved.

Key safety considerations include:

Ketoacidosis Risk: The medication increases ketoacidosis risk in type 1 diabetes patients, with type 2 diabetes and pancreatic disorders representing additional risk factors. Practitioners should assess baseline risk and monitor ketone levels in vulnerable populations.

Volume Management: Intravascular volume depletion may occur, potentially causing symptomatic hypotension or acute creatinine changes. Post-marketing surveillance identified acute kidney injury cases requiring dialysis in type 2 diabetes patients. Elderly patients and those receiving loop diuretics face heightened depletion risk.

Infection Risk: SGLT inhibitor therapy increases urinary tract infection susceptibility, including serious complications like urosepsis and pyelonephritis. Fournier’s gangrene, though rare, represents a life-threatening perineal necrotizing infection identified in post-marketing monitoring.

Metabolic Considerations: Genital mycotic infections occur more frequently, requiring routine monitoring. Concomitant insulin or insulin secretagogue use may necessitate dose reduction to mitigate hypoglycemia risk. Standard urinary glucose testing becomes unreliable and requires alternative methodology.

Common adverse reactions reported at ≥5% incidence included urinary tract infections, volume depletion, diarrhea, and hypoglycemia.

Drug Interaction Profile

Clinicians should note several important interactions: digoxin exposure increases substantially when combined with INPEFA 400 mg, requiring appropriate patient monitoring. Rifampicin, a UGT inducer, decreases sotagliflozin exposure. Lithium serum concentrations may decline with concomitant SGLT2 inhibitor use, necessitating more frequent monitoring during initiation and dosage adjustments.

Special Populations

No age-based dosage modifications are required for geriatric patients, though increased sensitivity to volume depletion adverse effects warrants heightened vigilance. INPEFA is not recommended during pregnancy’s second and third trimesters or during lactation. Patients with chronic kidney disease (eGFR 25-60 mL/min/1.73 m²) were included in clinical trials, supporting use in moderate renal impairment.

Clinical Timeline and Availability

Lexicon Pharmaceuticals anticipates INPEFA commercial availability by end of June 2023, with wholesale acquisition costs comparable to existing branded heart failure medications. The company will host management discussions on May 30, 2023, providing additional detail on this approval.