Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced that the
Company will present 11 abstracts, including two late-breaking oral
presentations, at the upcoming American Society of Nephrology (ASN)
Kidney Week 2023 in Philadelphia, PA, November 2-5, 2023.
Presentations will highlight the long-term efficacy and
tolerability data of FILSPARI® (sparsentan) in IgA nephropathy
(IgAN) from the PROTECT Study, as well as the potential for use of
FILSPARI as a first-line treatment in newly diagnosed IgAN patients
and in combination with SGLT2 inhibitors. The Company will also
present data on the efficacy and tolerability of sparsentan in
focal segmental glomerulosclerosis (FSGS) and pediatric proteinuric
glomerular diseases, as well as provide insights into patient
quality of life and the impact of proteinuria on kidney survival in
rare kidney diseases.
“The data we and our collaborators are presenting at ASN are a
testament to our collective dedication to enhance our scientific
understanding of kidney diseases to improve patients’ lives,” said
Jula Inrig, M.D., chief medical officer of Travere Therapeutics.
“We look forward to presenting data that further demonstrate the
clinical benefit of sparsentan in rare kidney diseases and sharing
important advancements that have the potential to shape the future
of patient care.”
Late-Breaker Oral Presentations
Sparsentan vs Irbesartan in Patients with Focal
Segmental Glomerulosclerosis (FSGS): Results from the Phase 3
DUPLEX TrialAbstract: FR-OR108Oral Abstract Session: High
Impact Clinical TrialsHall A; November 3, 10:30-10:45 a.m. ET
Pivotal Results of the Phase 3 PROTECT Trial of
Sparsentan vs Irbesartan in Patients with Immunoglobulin A
Nephropathy (IgAN)Abstract: FR-OR109Oral Abstract Session:
High Impact Clinical TrialsHall A; November 3, 10:45-11:00 a.m.
ET
Oral Presentation
Preliminary Findings from the Phase 2 EPPIK Study of
Sparsentan in Pediatric Patients with Selected Proteinuric
Glomerular DiseasesAbstract: SA-OR84Oral Abstract Session:
Pediatric Nephrology: Clinical and Genetic Studies Room 105;
November 4, 5:24-5:33 p.m. ET
Poster Presentations
Humanistic Burden of Rare Kidney Diseases: Understanding
the Impact of IgAN and FSGS on Patients & Care-partners Study
(HONUS): Preliminary Results for FSGS in the United States
(US)Poster: TH-PO597Poster Session: Glomerular Diseases:
Clinical and Epidemiologic StudiesExhibit Hall; November 2, 10:00
a.m.-12:00 p.m. ET
Predictors of Major Adverse Kidney Disease Events in a
Real-world Population with IgA NephropathyPoster:
TH-PO614Poster Session: Glomerular Diseases: Clinical and
Epidemiologic StudiesExhibit Hall; November 2, 10:00 a.m.-12:00
p.m. ET
Comparing Proteinuria and Kidney Survival in FSGS and
IgAN: A NEPTUNE AnalysisPoster: TH-PO622Poster Session:
Glomerular Diseases: Clinical and Epidemiologic StudiesExhibit
Hall; November 2, 10:00 a.m.-12:00 p.m. ET
Sparsentan as First-line Treatment of Incident Patients
with IgA Nephropathy: Preliminary Findings from the SPARTAN
TrialPoster: SA-PO901Poster Session: Glomerular Diseases:
TherapeuticsExhibit Hall; November 4, 10:00 a.m.-12:00 p.m. ET
Sparsentan Receptor Occupancy Modeling, Clinical
Actions, and SafetyPoster: SA-PO276Poster Session:
Pharmacology: Kinetics, Genomics, Medication-Related
ProblemsExhibit Hall; November 4, 10:00 a.m.-12:00 p.m. ET
Concomitant Sparsentan and Sodium-glucose
Cotransporter-2 Inhibitors (SGLT2i) in Patients with IgA
Nephropathy (IgAN) in the PROTECT Open-label Extension
(OLE)Poster: SA-PO903Poster Session: Glomerular Diseases:
TherapeuticsExhibit Hall; November 4, 10:00 a.m.-12:00 p.m. ET
Rate of Loss of eGFR and Time-averaged Proteinuria in
IgAN Patients Progressing from Early Stage Disease to Kidney
FailurePoster: SA-PO948Poster Session: Glomerular
Diseases: Translational Studies and BiomarkersExhibit Hall;
November 4, 10:00 a.m.-12:00 p.m. ET
Sparsentan and Sodium-glucose Cotransporter 2 Inhibitors
(SGLT2i) in the PROTECT Open-label extension (OLE) Substudy and
SPARTACUS: Trials in ProgressPoster: SA-PO902Poster
Session: Glomerular Diseases: TherapeuticsExhibit Hall; November 4,
10:00 a.m.-12:00 p.m. ET
About IgA Nephropathy
IgA nephropathy (IgAN), also called Berger's disease, is a rare
progressive kidney disease characterized by the buildup of
immunoglobulin A (IgA), a protein that helps the body fight
infections, in the kidneys. The deposits of IgA cause a breakdown
of the normal filtering mechanisms in the kidney, leading to blood
in the urine (hematuria), protein in the urine (proteinuria) and a
progressive loss of kidney function. Other symptoms of IgAN may
include swelling (edema) and high blood pressure.
IgAN is the most common type of primary glomerulonephritis
worldwide and a leading cause of kidney failure due to glomerular
disease. IgAN is estimated to affect up to 150,000 people in the
U.S. and is one of the most common glomerular diseases in Europe
and Japan.
About Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS) is a rare proteinuric
kidney disorder in both children and adults that is estimated to
affect more than 40,000 patients in the US with similar prevalence
in Europe. The disorder is defined by progressive scarring of the
kidney and often leads to kidney failure. FSGS is characterized by
proteinuria, where protein leaks into the urine due to a breakdown
of the normal filtration mechanism in the kidney. Once in the
urine, protein is considered to be toxic to other parts of the
kidney, especially the tubules, and is believed to contribute to
further disease progression. Other common symptoms include swelling
in parts of the body, known as edema, as well as low blood albumin
levels, abnormal lipid profiles and hypertension. There is
currently no approved pharmacologic indicated for the treatment of
FSGS.
About the PROTECT Study
The PROTECT Study is one of the largest interventional studies
to date in IgA nephropathy (IgAN) and the only head-to-head trial
in this rare kidney disease. It is a global, randomized,
multicenter, double-blind, parallel-arm, active-controlled clinical
trial evaluating the safety and efficacy of 400 mg of sparsentan,
compared to 300 mg of irbesartan, in 404 patients ages 18 years and
up with IgAN and persistent proteinuria despite receiving at least
50% of max label dose and maximally tolerated ACE or ARB therapy.
In August 2021, the Company announced the PROTECT Study met
its pre-specified interim primary efficacy endpoint with
statistical significance. Based on the pre-specified, primary
analyses set, after 36 weeks of treatment, patients receiving
sparsentan achieved a mean reduction in proteinuria from baseline
of 49.8%, compared to a mean reduction in proteinuria from baseline
of 15.1% for irbesartan-treated patients (p<0.0001). The study’s
confirmatory secondary endpoint in the U.S. is eGFR total
slope from day 1 to week 110 of treatment. The confirmatory
secondary endpoint in the EU is eGFR chronic slope from week 6 to
week 110 of treatment, following the initial acute effect of
randomized treatment. Following the 110-week blinded treatment
period, treatment with study medication is discontinued for 4 weeks
-- at this time, the investigator resumes standard of care
treatment. Patients that completed the PROTECT double-blind portion
of the study on treatment were eligible to participate in the
open-label portion of the trial.
About the DUPLEX Study
The DUPLEX Study is the largest interventional study to date in
FSGS. It is a global, randomized, multicenter, double-blind,
parallel-arm, active-controlled Phase 3 clinical trial assessing
the efficacy and safety of sparsentan in 371 patients ages 8 to 75
years with primary FSGS. After a two-week washout period, patients
are randomized 1:1 to receive either sparsentan or irbesartan, the
active control, and subsequently dose titrated to the maximum dose
of 800 mg of sparsentan or 300 mg of irbesartan, as tolerated.
In February 2021, the Company announced that the ongoing
pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its
pre-specified interim FSGS partial remission of proteinuria (FPRE)
endpoint with statistical significance. FPRE is a clinically
meaningful endpoint defined as urine protein-to-creatinine ratio
(UP/C) ≤1.5 g/g and a >40 percent reduction in UP/C from
baseline. After 36 weeks of treatment, 42.0% of patients receiving
sparsentan achieved FPRE, compared to 26.0% of irbesartan-treated
patients (p=0.0094). Preliminary results from the interim analysis
suggest that at the time of the interim assessment, sparsentan had
been generally well-tolerated and shown a comparable safety profile
to irbesartan. The study’s primary efficacy endpoint in the U.S. is
the eGFR total slope from day 1 to week 108 of treatment. The
primary efficacy endpoint in Europe is the eGFR chronic
slope, from week 6 to week 108 of treatment, following the initial
acute effect of randomized treatment. Patients that completed the
DUPLEX double-blind portion of the study on treatment were eligible
to participate in the open-label portion of the trial.
About the SPARTACUS Study
The SPARTACUS Study aims to evaluate the safety and effect of
sparsentan in combination with SGLT2 inhibitor therapy in
approximately 60 adult IgAN patients at risk of disease progression
to kidney failure. In this 28-week, open-label, multi-center,
single-group Phase 2 exploratory study, eligible participants on
stable SGLT2 inhibitor dosing are administered sparsentan (target
dose of 400 mg) for 24 weeks after discontinuation of standard of
care ACEI and/or ARB treatment, followed by a 4-week safety
follow-up period. The study will evaluate safety and efficacy
outcomes including change in proteinuria from baseline and
achievement of remission of proteinuria-based endpoints through
week 24. Patient enrollment is ongoing and the study is anticipated
to readout in 2025.
About the SPARTAN Study
The SPARTAN Study a multi-center, open-label, single-group trial
exploring the safety and response to first-line sparsentan
treatment in newly diagnosed, renin angiotensin system (RAS)
blockade-naïve adult patients with biopsy-proven IgAN. The study is
a collaboration between Travere Therapeutics and the University of
Leicester (Study Sponsor) and is being conducted in 5 hospitals in
the UK. Participants (n=12) are administered sparsentan (target
dose of 400 mg) for 110 weeks, followed by a 4-week safety period.
In addition to established safety and efficacy assessments,
including incidence of adverse events, change in proteinuria and
eGFR, the mechanistic actions of sparsentan are explored through
renal MRI assessments and analyses comparing diagnostic biopsies
with repeat biopsies performed at week 24. The study is fully
enrolled, with final readout scheduled for 2025.
FILSPARI®
(sparsentan) U.S. Indication
FILSPARI is an endothelin and angiotensin II
receptor antagonist indicated to reduce proteinuria in adults with
primary immunoglobulin A nephropathy (IgAN) at risk of rapid
disease progression, generally a UPCR ≥1.5 g/g.
This indication is granted under accelerated
approval based on reduction in proteinuria. It has not been
established whether FILSPARI slows kidney function decline in
patients with IgAN. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory clinical trial.
FILSPARI®
(sparsentan) Important Safety Information
BOXED WARNING: HEPATOTOXICITY AND
EMBRYO-FETAL TOXICITYBecause of the risks of
hepatotoxicity and birth defects, FILSPARI is available only
through a restricted program called the FILSPARI REMS. Under the
FILSPARI REMS, prescribers, patients and pharmacies must enroll in
the program.
HepatotoxicitySome
Endothelin Receptor Antagonists (ERAs) have caused elevations of
aminotransferases, hepatotoxicity, and liver failure. In clinical
studies, elevations in aminotransferases (ALT or AST) of at least
3-times the Upper Limit of Normal (ULN) have been observed in up to
2.5% of FILSPARI-treated patients, including cases confirmed with
rechallenge.
Measure transaminases and bilirubin
before initiating treatment and monthly for the first 12 months,
and then every 3 months during treatment. Interrupt treatment and
closely monitor patients who develop aminotransferase elevations
more than 3x ULN.
FILSPARI should generally be avoided in
patients with elevated aminotransferases (>3x ULN) at baseline
because monitoring for hepatotoxicity may be more difficult and
these patients may be at increased risk for serious
hepatotoxicity.
Embryo-Fetal
ToxicityFILSPARI can cause major birth defects if
used by pregnant patients based on animal data. Therefore,
pregnancy testing is required before the initiation of treatment,
during treatment and one month after discontinuation of treatment
with FILSPARI. Patients who can become pregnant must use effective
contraception before the initiation of treatment, during treatment,
and for one month after discontinuation of treatment with
FILSPARI.
Contraindications: FILSPARI is
contraindicated in patients who are pregnant. Do not coadminister
FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or
aliskiren.
Warnings and Precautions
Hepatotoxicity: Elevations in ALT or AST of at
least 3-fold ULN have been observed. To reduce the risk of
potential serious hepatotoxicity, measure serum aminotransferase
levels and total bilirubin prior to initiation of treatment,
monthly for the first 12 months, then every 3 months during
treatment.
Advise patients with symptoms suggesting
hepatotoxicity (nausea, vomiting, right upper quadrant pain,
fatigue, anorexia, jaundice, dark urine, fever, or itching) to
immediately stop treatment with FILSPARI and seek medical
attention. If aminotransferase levels are abnormal at any time
during treatment, interrupt FILSPARI and monitor as
recommended.
Consider re-initiation of FILSPARI only when
hepatic enzyme levels and bilirubin return to pretreatment values
and only in patients who have not experienced clinical symptoms of
hepatotoxicity.
Avoid initiation of FILSPARI in patients with
elevated aminotransferases (>3x ULN) prior to drug
initiation.
Embryo-Fetal Toxicity: FILSPARI
can cause fetal harm. Advise patients who can become pregnant of
the potential risk to a fetus. Obtain a pregnancy test and advise
patients who can become pregnant to use effective contraception
prior to, during, and one month after discontinuation of FILSPARI
treatment.
FILSPARI REMS: FILSPARI is
available only through a restricted program under a REMS called the
FILSPARI REMS.
Important
requirements include:
- Prescribers must be
certified with the FILSPARI REMS by enrolling and completing
training.- All patients must enroll in the FILSPARI REMS prior to
initiating treatment and comply with monitoring requirements.-
Pharmacies that dispense FILSPARI must be certified with the
FILSPARI REMS and must dispense only to patients who are authorized
to receive FILSPARI.
Further information is available at
www.filsparirems.com or 1-833-513-1325.
Hypotension: There was a
greater incidence of hypotension-associated adverse events, some
serious, including dizziness, in patients treated with FILSPARI
compared to irbesartan. In patients at risk for hypotension,
consider eliminating or adjusting other antihypertensive
medications and maintaining appropriate volume status. If
hypotension develops, consider a dose reduction or dose
interruption of FILSPARI.
Acute Kidney Injury: Monitor
kidney function periodically. Patients whose kidney function may
depend in part on the activity of the renin-angiotensin system
(e.g., patients with renal artery stenosis, chronic kidney disease,
severe congestive heart failure, or volume depletion) may be at
particular risk of developing acute kidney injury on FILSPARI.
Consider withholding or discontinuing therapy in patients who
develop a clinically significant decrease in kidney function while
on FILSPARI.
Hyperkalemia: Monitor serum
potassium periodically and treat appropriately. Patients with
advanced kidney disease, taking concomitant potassium-increasing
drugs (e.g., potassium supplements, potassium-sparing diuretics),
or using potassium-containing salt substitutes are at increased
risk for developing hyperkalemia. Dosage reduction or
discontinuation of FILSPARI may be required.
Fluid Retention: Fluid
retention may occur with ERAs, and has been observed with FILSPARI.
If clinically significant fluid retention develops, after
evaluation, consider modifying the dose of FILSPARI.
Most common adverse reactions (5%) with
FILSPARI are peripheral edema, hypotension (including
orthostatic hypotension), dizziness, hyperkalemia, and anemia.
Drug interactions
- Renin-Angiotensin System
(RAS) Inhibitors and ERAs: Do not coadminister FILSPARI
with angiotensin receptor blockers (ARBs), ERAs, or aliskiren.
- Strong and Moderate CYP3A
Inhibitors: Avoid concomitant use of FILSPARI with strong
CYP3A inhibitors. Monitor blood pressure, serum potassium, edema,
and kidney function regularly when used concomitantly with moderate
CYP3A inhibitors.
- Strong CYP3A
Inducers: Avoid concomitant use with a strong CYP3A
inducer.
- Antacids and Acid Reducing
Agents: Administer FILSPARI 2 hours before or after
administration of antacids. Avoid concomitant use of acid reducing
agents (histamine H2 receptor antagonist and PPI proton pump
inhibitor) with FILSPARI.
- Non-Steroidal
Anti-Inflammatory Agents (NSAIDs), Including Selective
Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of
worsening renal function.
- CYP2B6, 2C9, and 2C19
Substrates: Monitor for efficacy of the concurrently
administered CYP2B6, 2C9, and 2C19 substrates and consider dosage
adjustment in accordance with the Prescribing Information.
- P-gp and BCRP Substrates:
Avoid concomitant use of sensitive substrates of P-gp and
BCRP with FILSPARI.
- Agents Increasing Serum
Potassium: Monitor serum potassium frequently. Concomitant
use of FILSPARI with potassium-sparing diuretics, potassium
supplements, potassium-containing salt substitutes, or other drugs
that raise serum potassium levels may result in hyperkalemia.
Use in specific populations
- Pregnancy / Females and
Males of Reproductive Potential: FILSPARI can cause fetal
harm, including birth defects and fetal death, when administered to
a pregnant patient and is contraindicated during pregnancy.
- Pregnancy Testing /
Contraception: Verify the pregnancy status and effective
method of contraception prior to, during, and one month after
discontinuation of FILSPARI treatment. The patient should contact
their physician immediately for pregnancy testing if onset of
menses is delayed or pregnancy is suspected.
- Lactation: Advise
patients not to breastfeed during treatment with FILSPARI.
- Hepatic
Impairment: Avoid use of FILSPARI in patients with any
hepatic impairment (Child-Pugh class A-C).
Please see Full Prescribing Information
for FILSPARI here.
About Travere Therapeutics
At Travere Therapeutics, we are in rare for
life. We are a biopharmaceutical company that comes together every
day to help patients, families and caregivers of all backgrounds as
they navigate life with a rare disease. On this path, we know the
need for treatment options is urgent – that is why our global team
works with the rare disease community to identify, develop and
deliver life-changing therapies. In pursuit of this mission, we
continuously seek to understand the diverse perspectives of rare
patients and to courageously forge new paths to make a difference
in their lives and provide hope – today and tomorrow. For more
information, visit travere.comForward Looking
Statements
This press release contains “forward-looking statements” as that
term is defined in the Private Securities Litigation Reform Act of
1995. Without limiting the foregoing, these statements are often
identified by the words “anticipate,” “believe,” “expect,”
“intend,” “may,” “might,” “objective,” “plan,” “will” or similar
expressions. In addition, expressions of our strategies, intentions
or plans are also forward-looking statements. Such forward-looking
statements include, but are not limited to, references to the
potential effect of FILSPARI (sparsentan) as a first-line treatment
in newly diagnosed IgAN patients and in combination with SGLT2
inhibitors, references to data on the long-term efficacy and
tolerability of FILSPARI in IgAN, references to data on the
efficacy and tolerability of sparsentan in FSGS and pediatric
proteinuric glomerular diseases, anticipated readout dates, and
references to PROTECT, DUPLEX, and the other studies referenced
herein. Such forward-looking statements are based on current
expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them,
and could cause actual outcomes and results to differ materially
from current expectations. No forward-looking statement can be
guaranteed. Among the factors that could cause actual results to
differ materially from those indicated in the forward-looking
statements are risks and uncertainties associated with the
regulatory review and approval process, risks associated with
enrollment of clinical trials for rare diseases, and risks that
ongoing or planned clinical trials may not succeed or may be
delayed for safety, regulatory or other reasons. The Company faces
risks related to the commercial launch of a new product; risks
associated with market acceptance of FILSPARI and other current and
future products, including efficacy, safety, price, reimbursement
and benefit over competing therapies; the risk that the results of
the Phase 3 PROTECT Study of sparsentan in IgAN will not be deemed
sufficient by the FDA to serve as the basis for an sNDA submission
for traditional approval of sparsentan; and the risk that the
results from the Phase 3 DUPLEX study of sparsentan in FSGS will
not serve as a basis for a regulatory submission for approval of
sparsentan for FSGS. There is no guarantee that regulators will
grant full approval of sparsentan for IgAN or FSGS. The Company
also faces risk that it will be unable to raise additional funding
that may be required to complete development of any or all of its
product candidates, including as a result of macroeconomic
conditions; risks relating to the Company's dependence on
contractors for clinical drug supply and commercial manufacturing;
uncertainties relating to patent protection and exclusivity periods
and intellectual property rights of third parties; risks associated
with regulatory interactions; and risks and uncertainties relating
to competitive products, including current and potential future
generic competition with certain of the Company's products, and
technological changes that may limit demand for the Company's
products. The Company also faces additional risks associated with
global and macroeconomic conditions, including health epidemics and
pandemics, including risks related to potential disruptions to
clinical trials, commercialization activity, supply chain, and
manufacturing operations. You are cautioned not to place undue
reliance on these forward-looking statements as there are important
factors that could cause actual results to differ materially from
those in forward-looking statements, many of which are beyond our
control. The Company undertakes no obligation to publicly update
any forward-looking statement, whether as a result of new
information, future events, or otherwise. Investors are referred to
the full discussion of risks and uncertainties, including under the
heading “Risk Factors”, as included in the Company’s most recent
Form 10-K, Form 10-Q and other filings with the Securities and
Exchange Commission.
Contact Info
Media:Nivi NehraVice President,
Corporate
Communications888-969-7879 mediarelations@travere.com |
Investors:Naomi EichenbaumVice
President, Investor
Relations888-969-7879 IR@travere.com |
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