Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that
the U.S. Food and Drug Administration (FDA) has approved INPEFA™
(sotagliflozin), a once-daily oral tablet 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.
The broad label encompasses heart failure
patients across the full range of left ventricular ejection
fraction (LVEF), including preserved ejection fraction and reduced
ejection fraction, and for patients with or without diabetes.
“The approval of INPEFA along with the breadth
of the label, is a major milestone in Lexicon’s path to fulfilling
its mission of pioneering medicines that transform patients’
lives,” said Lonnel Coats, Lexicon’s chief executive officer. “We
expect this important innovation to be commercially available in
the U.S. market by the end of June 2023.”
The approval is based on two randomized,
double-blind, placebo-controlled Phase 3 cardiovascular outcomes
studies of INPEFA in patients with heart failure or at risk of
heart failure. Together, SOLOIST-WHF (Worsening Heart Failure) and
SCORED enrolled almost 12,000 patients. Results from SOLOIST-WHF
showed that INPEFA significantly reduced risk of the composite of
hospitalizations for heart failure, urgent visits for heart
failure, and cardiovascular death by 33% compared to placebo in
patients who had been recently hospitalized for worsening heart
failure.
INPEFA is an inhibitor of both sodium-glucose
co-transporter type 2 (SGLT2) and type 1 (SGLT1). The SGLT
inhibitor class was recommended as first-line treatment for heart
failure by the American Heart Association (AHA), the American
College of Cardiology (ACC), and the Heart Failure Society of
America (HFSA) in their joint 2022 AHA/ACC/HFSA Guideline for the
Management of Heart Failure. An April 2023 ACC expert consensus
statement highlighted the benefit of SGLT inhibitors as part of
Guideline-Directed Medical Therapy (GDMT) in patients with heart
failure with preserved ejection fraction (HFpEF). According to the
ACC expert consensus statement, SGLT2 inhibitors should be
initiated in all individuals with HFpEF who are stable during
hospitalization and have no patient population
contraindications.
About 6.7 million Americans suffer from heart
failure, with the prevalence expected to rise to 8.0 million by
2030. Heart failure is the leading cause of hospitalizations for
individuals aged 65 and older, triggering approximately 1.3 million
hospitalizations a year. Patients with heart failure are at highest
risk of a heart failure event in the first 30 days post-discharge,
with 7% dying and 25% being rehospitalized within one month.
“Based on outcomes observed in the SOLOIST-WHF
study, initiating treatment with INPEFA prior to or upon hospital
discharge has the potential to reduce the burden of readmissions on
patients, caregivers, providers, and health systems,” said Craig
Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief
medical officer. “With today’s FDA approval, INPEFA is now a
valuable option for physicians to consider when treating patients
transitioning out of the hospital and working to break the cycle of
repeated hospitalizations.”
Lexicon expects INPEFA to be available by the
end of June 2023. The company plans to set the medicine’s wholesale
acquisition cost comparable to existing branded heart failure
medications.
Conference Call and Webcast
Information
Lexicon management will hold a live conference
call and webcast Tuesday, May 30, 2023, at 8:00 am ET / 7:00 am CT.
The dial-in number for the conference call is 888-317-6003 and the
conference ID for all callers is 0516154. The live webcast and
replay may be accessed by visiting Lexicon’s website at
www.lexpharma.com/events. An archived version of the webcast will
be available on the website for 14 days.
About INPEFA™
(sotagliflozin)
Discovered using Lexicon’s unique approach to
gene science, INPEFA™ (sotagliflozin) is an oral inhibitor of two
proteins responsible for glucose regulation known as sodium-glucose
cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible
for glucose reabsorption by the kidney and SGLT1 is responsible for
glucose absorption in the gastrointestinal tract. Sotagliflozin has
been studied in multiple patient populations encompassing heart
failure, diabetes, and chronic kidney disease in clinical studies
involving approximately 20,000 patients.
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
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 hypersensitivity to INPEFA or any
of its components.
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.
Click here for full Prescribing
Information.
About Heart Failure
About 6.7 million Americans suffer from heart
failure, a progressive, debilitating condition that is becoming
more prevalent. Heart failure is the leading cause of
hospitalizations for individuals aged 65 and older, triggering
approximately 1.3 million hospitalizations a year.
About the SOLOIST-WHF Study
SOLOIST-WHF was a multi-center, randomized,
double-blinded, placebo-controlled Phase 3 study evaluating the
cardiovascular efficacy of sotagliflozin versus placebo when added
to standard of care in 1,222 patients with type 2 diabetes who had
recently been hospitalized for worsening heart failure. The primary
endpoint was the total number of events comprised of deaths from
cardiovascular causes, hospitalizations for heart failure, and
urgent visits for heart failure in patients treated with
sotagliflozin compared with placebo.
SOLOIST-WHF achieved its primary endpoint, with
overall tolerability similar to placebo. Results were presented at
the Late-Breaking Science Session of the American Heart Association
(AHA) Scientific Sessions 2020 and simultaneously published in The
New England Journal of Medicine (NEJM) in an article titled:
“Sotagliflozin in Patients with Diabetes and Recent Worsening Heart
Failure.”
About the SCORED Study
SCORED was a multi-center, randomized,
double-blinded, placebo-controlled Phase 3 study evaluating the
cardiovascular efficacy of sotagliflozin versus placebo when added
to standard of care in 10,584 patients with type 2 diabetes,
chronic kidney disease with eGFR of 25 ml to 60 ml per minute per
1.73 m2 of body-surface area, and risks for cardiovascular disease.
The primary endpoint was the total number of events comprised of
deaths from cardiovascular causes, hospitalizations for heart
failure, and urgent visits for heart failure in patients treated
with sotagliflozin compared with placebo. Key secondary endpoints
included total number of events of deaths from cardiovascular
causes, non-fatal myocardial infarction, and non-fatal stroke.
SCORED achieved its primary endpoint, with
overall tolerability similar to placebo. Results were presented at
the Late-Breaking Science Session of the American Heart Association
(AHA) Scientific Sessions 2020 and simultaneously published in The
New England Journal of Medicine (NEJM) in an article titled:
“Sotagliflozin in Patients with Diabetes and Chronic Kidney
Disease.”
About Lexicon
Pharmaceuticals
Lexicon is a biopharmaceutical company with a
mission of pioneering medicines that transform patients’ lives.
Through its Genome5000™ program, Lexicon scientists studied the
role and function of nearly 5,000 genes and identified more than
100 protein targets with significant therapeutic potential in a
range of diseases. Through the precise targeting of these proteins,
Lexicon is pioneering the discovery and development of innovative
medicines to treat diseases safely and effectively. Lexicon has
previously advanced one of these medicines to market and has a
pipeline of promising drug candidates in heart failure, neuropathic
pain, diabetes and metabolism and other indications. For additional
information, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains “forward-looking
statements,” including statements relating to the therapeutic and
commercial potential, research and clinical development and
regulatory status of INPEFA™ (sotagliflozin). In addition, this
press release also contains forward looking statements relating to
Lexicon’s financial position and long-term outlook on its business,
growth and future operating results, discovery and development of
products, strategic alliances and intellectual property, as well as
other matters that are not historical facts or information. All
forward-looking statements are based on management’s current
assumptions and expectations and involve risks, uncertainties and
other important factors, specifically including Lexicon’s ability
to meet its capital requirements, successfully commercialize INPEFA
in heart failure on the timeline and/or at the prices currently
contemplated or at all, conduct preclinical and clinical
development and obtain necessary regulatory approvals of INPEFA (in
other indications), LX9211 and its other drug candidates on its
anticipated timelines, achieve its operational objectives, obtain
patent protection for its discoveries and establish strategic
alliances, as well as additional factors relating to manufacturing,
intellectual property rights, and the therapeutic or commercial
value of its drug candidates. Any of these risks, uncertainties and
other factors may cause Lexicon’s actual results to be materially
different from any future results expressed or implied by such
forward-looking statements. Information identifying such important
factors is contained under “Risk Factors” in Lexicon’s annual
report on Form 10-K for the year ended December 31, 2022, quarterly
report on Form 10-Q for the quarter ended March 31, 2023 and other
subsequent disclosure documents filed with the Securities and
Exchange Commission. Lexicon undertakes no obligation to update or
revise any such forward-looking statements, whether as a result of
new information, future events or otherwise.
For Investor Inquiries:Carrie
SiragusaLexicon Pharmaceuticals, Inc.csiragusa@lexpharma.com
For Media Inquiries:Alina
CocuzzaLexicon Pharmaceuticals, Inc.acocuzza@lexpharma.com
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