Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced the
submission of a supplemental New Drug Application (sNDA) to the
U.S. Food and Drug Administration (FDA) for conversion of the
existing U.S. accelerated approval of FILSPARI
®
(sparsentan) in IgA nephropathy (IgAN) to full approval. In
February 2023, the FDA granted accelerated approval to FILSPARI as
the first and only non-immunosuppressive treatment targeting
glomerular injury in the kidney to reduce proteinuria in adults
with primary IgAN at risk of rapid disease progression. The sNDA is
based on 2-year confirmatory results from the Phase 3 PROTECT
Study, the only head-to-head study in IgAN versus an active
comparator.
“Since being introduced under accelerated approval, FILSPARI has
positively impacted the lives of many people living with IgAN. The
submission of the sNDA is an important step toward potentially
gaining full approval in IgAN in support of reaching more people
living with this devastating rare kidney disease,” said Eric Dube,
Ph.D., president and chief executive officer of Travere
Therapeutics. “FILSPARI is at the forefront of emerging new
treatment options providing hope for a delay in kidney transplant
or dialysis. The results from the pivotal Phase 3 PROTECT Study
show that by directly targeting glomerular injury in the kidney
with FILSPARI, patients can achieve sustained proteinuria reduction
and long-term kidney function preservation. We look forward to
working with the FDA throughout the upcoming review process.”
FILSPARI is a once-daily, oral medication that directly targets
glomerular injury in the kidney by blocking two critical pathways
of IgAN disease progression (endothelin-1 and angiotensin II).
FILSPARI is also the first and only non-immunosuppressive therapy
approved for the treatment of this rare kidney disease. The sNDA
submission is supported by results from the Phase 3 PROTECT Study
that showed that FILSPARI demonstrated long-term kidney function
preservation and achieved a significant reduction in proteinuria
and a clinically meaningful difference in eGFR slope versus an
active comparator.
The FDA has 60 days from the receipt of the application to
determine whether to accept it for review. The Company expects to
receive notice regarding the acceptance for review of the sNDA
submission as well as the timeline for sNDA review from the FDA in
the second quarter of 2024. In addition to the sNDA submission to
the FDA, the Company and its European commercial partner CSL Vifor
recently announced that the European Medicines Agency’s (EMA)
Committee for Medicinal Products for Human Use (CHMP) has
recommended approval of the conditional marketing authorization
(CMA) for sparsentan for the treatment of IgA nephropathy (IgAN) in
Europe. A decision by the European Commission is expected in the
second quarter of 2024. If approved, sparsentan would receive a CMA
in all member states of the European Union, as well as
in Iceland, Liechtenstein, and Norway.
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 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 estimated
glomerular filtration rate (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
was discontinued for 4 weeks -- at this time, the investigator
resumed standard of care treatment. In September 2023, the
Company announced topline two-year confirmatory secondary endpoint
results from the PROTECT Study of sparsentan in IgAN.
Sparsentan demonstrated long-term kidney function preservation and
achieved a clinically meaningful difference in eGFR total and
chronic slope versus irbesartan, narrowly missing statistical
significance in eGFR total slope while achieving statistical
significance in eGFR chronic slope for purposes of regulatory
review in the EU. Patients who completed the PROTECT double-blind
portion of the study on treatment were eligible to participate in
the open-label extension of the trial.
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.com
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.
Forward 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 “on-track,” “positioned,” “look forward
to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,”
“plans,” “expects,” “intends,” “potential,” 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: statements and
expectations regarding the FDA’s potential acceptance for filing of
the sNDA submission for FILSPARI in IgAN and the anticipated
timeline and outcome of the FDA’s review of the sNDA; statements
regarding the potential conditional marketing authorization of
sparsentan for the treatment of IgAN in the European Union,
Iceland, Liechtenstein and Norway and the anticipated timing
thereof, including the potential timing and outcome of the European
Commission’s decision; and the potential for emerging new treatment
options for IgAN that have the potential to provide hope for a
delay in kidney transplant or a dialysis. 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, as well as risks
and uncertainties associated with the Company’s business and
finances in general, the success of its commercial products and
risks and uncertainties associated with the Company’s preclinical
and clinical stage pipeline. Specifically, the Company faces risks
associated with market acceptance of its commercial products
including efficacy, safety, price, reimbursement, and benefit over
competing therapies, as well as risks associated with the
successful development and execution of commercial strategies for
such products, including FILSPARI. The risks and uncertainties the
Company faces with respect to its preclinical and clinical stage
pipeline include risk that the Company’s clinical candidates will
not be found to be safe or effective and that current or
anticipated future clinical trials will not proceed as planned.
Specifically, the Company faces risks related to the timing and
potential outcome of the FDA’s potential acceptance for filing and
review of the sNDA submission for full approval of FILSPARI in
IgAN, and the timing and potential outcome of the European
Commission’s decision regarding conditional marketing authorization
of sparsentan for IgAN. There is no guarantee that the FDA will
accept the sNDA submission for filing, that the European Commission
will grant conditional marketing authorization of sparsentan for
IgAN, or that regulators will grant full approval of sparsentan for
IgAN. The Company also faces the 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:888-969-7879mediarelations@travere.com
|
Investors:888-969-7879IR@travere.com |
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