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Soloist‑WHF

INPEFA™ demonstrated significant efficacy in reducing the risk of CV death, hospitalization for HF, and urgent HF visit, regardless of EF1

SOLOIST‑WHF—a multi-center, randomized, double‑blind, placebo‑controlled, Phase 3 study in patients with type 2 diabetes mellitus who had been admitted to the hospital, heart failure unit, infusion center, or emergency department for worsening HF (N=1,222), evaluating the cardiovascular efficacy and safety of INPEFA™ (n=608) versus placebo (n=614) when added to standard of care.1

Assigned treatment was initiated in the hospital or within a median of 2 days following hospital discharge.1

33%risk reduction*

in the primary composite endpoint of CV death, hospitalization for HF, and urgent HF visit1

HR 0.67 (95% CI: 0.53, 0.85) p=0.001

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Additionally, a post hoc analysis in patients initiated on or before discharge showed:

>50% risk reduction*
in readmission for HF‑related event or CV death within 30 days2

HR 0.49 (95% CI: 0.27, 0.91)

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Limitations of post hoc analysis: This analysis occurred after the protocol-specified final analysis.2 No formal statistical testing was planned for this analysis therefore no conclusions can be drawn. This data is not in the US Prescribing Information and results should be interpreted with caution.

An incredibly low NNT of 43Number Needed to Treat to prevent 1 primary composite event of CV death, hospitalization for HF, and urgent HF visit3,†

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Limitations of post hoc analysis: This analysis occurred after the protocol-specified final analysis.2 No formal statistical testing was planned for this analysis therefore no conclusions can be drawn. This data is not in the US Prescribing Information and results should be interpreted with caution.

ARR=absolute risk reduction; CV=cardiovascular; EF=ejection fraction; HF=heart failure.

*Relative risk reduction.

†Calculation: The rate of primary endpoint events was 51.3 events per 100 patient years in the INPEFA™ group and 76.4 events per 100 patient years in the placebo group. Absolute difference=76.4‑51.3=25.1, NNT=1/ARR=1/0.25=4.4

33% risk reduction* in the primary composite endpoint of CV death, hospitalization for HF, and urgent HF visit1

In a cumulative events plot of the primary composite endpoint, INPEFA™ and placebo event curves diverged early and remained separated over the study period.1

Primary Endpoint1,2

Primary endpoint graph from the SOLOIST-WHF trial

Primary composite endpoint (total occurrences of CV death, hospitalization for HF, and urgent HF visit) was based on investigator-reported events in all randomized patients, analyzed according to the treatment group allocated by randomization.1

CI=confidence interval; HR=hazard ratio.

Post Hoc Analysis2

>50% risk reduction in readmission for HF‑related event or CV death within 30 days2

Readmission for HF‑related event or CV death within 30 and 90 days from hospital discharge‡

Post hoc analysis graph from the SOLOIST-WHF trial

Limitations of analysis: This post hoc analysis occurred after the protocol-specified final analysis.2 No formal statistical testing was planned for this analysis, therefore no conclusions can be drawn. This data is not in the USPI and results should be interpreted with caution.

USPI=United States Prescribing Information.

‡Patients included in this analysis received INPEFA™ prior to discharge in either the hospital or urgent care setting.2

The INPEFA™ safety profile in the 30‑ and 90‑day post-randomization windows was generally consistent with that observed for the overall study duration.2

An incredibly low

NNT of 43

Number Needed to Treat to prevent 1 primary composite event of CV death, hospitalization for HF, and urgent HF visit3,§

§Calculation: The rate of primary endpoint events was 51.3 events per 100 patient years in the INPEFA™ group and 76.4 events per 100 patient years in the placebo group. Absolute difference=76.4‑51.3=25.1, NNT=1/ARR=1/0.25=4.4

INPEFA™ SOLOIST‑WHF study adverse events

Adverse reactions reported in ≥2% of patients treated with INPEFA™ and at greater frequency than placebo.1

SOLOIST‑WHF(N=1,216)
Adverse Reaction
INPEFA™(n=605)
Placebo(n=611)
Urinary tract infection8.6%7.2%
Volume depletion9.3%8.8%
Diarrhea6.9%4.1%
Hypoglycemia4.3%2.8%
Dizziness2.6%2.5%
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References:

1. INPEFA [prescribing information]. Lexicon Pharmaceuticals Inc.; May 2023. 2. Data on File. 3. Verma S, Anker SD, Butler J, Bhatt DL. Early initiation of SGLT2 inhibitors is important, irrespective of ejection fraction: SOLOIST-WHF in perspective. ESC Heart Failure. 2020;7(6):3261-3267. doi:10.1002/ehf2.13148 4. Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117-128. doi:10.1056/NEJMoa2030183

Important Safety Information

Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA. INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge.

Contraindications: INPEFA is contraindicated in patients with a history of serious hypersensitivity reaction to INPEFA.

Warnings and Precautions:

  • Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type 2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk factors. The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis and educate patients on the signs/symptoms of ketoacidosis. Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. INPEFA is not indicated for glycemic control. Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level. If suspected, discontinue INPEFA, evaluate, and treat promptly. Monitor patients for resolution of ketoacidosis before restarting INPEFA.
  • Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy.
  • Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly.
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA.
  • Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure.
  • Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate.
  • Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: These are not reliable for patients taking SGLT2 inhibitors. Use alternative testing methods to monitor glucose levels.

Common Adverse Reactions: The most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.

Drug Interactions:

  • Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg.
  • Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.
  • Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes.

Use in Specific Populations:

  • Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.
  • Geriatric Use: No INPEFA dosage change is recommended based on age. No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.
  • Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2. The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile. There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73m2 relative to the overall safety population. Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.
  • Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment.

Indication

INPEFA™ is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:

  • heart failure or
  • type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors

Please see full Prescribing Information and Patient Medication Guide.