Travere Therapeutics, Inc., (Nasdaq: TVTX) today announced
that the U.S. Food and Drug Administration (FDA) has granted full
approval to FILSPARI® (sparsentan) to slow kidney function decline
in adults with primary IgAN who are at risk of disease progression.
FILSPARI was granted accelerated approval in February 2023 based on
the surrogate marker of proteinuria. Full approval is based on
positive long-term confirmatory results from the PROTECT Study
demonstrating that FILSPARI significantly slowed kidney function
decline over two years compared to irbesartan.
“We know that most people living with IgAN are
at risk of disease progression and are seeking a safe, effective
and convenient treatment option that can help preserve their kidney
function. Full approval now enables physicians to confidently
prescribe FILSPARI more broadly as a once-daily, oral,
non-immunosuppressive treatment, that can provide superior
preservation of kidney function and replace current standard of
care,” said Eric Dube, Ph.D., president and chief executive officer
of Travere Therapeutics. “With KDIGO’s recent draft guidelines
recommending FILSPARI as a foundational kidney-targeted therapy and
lowering the targeted proteinuria level for all IgAN patients to
under 0.5 g/day or 0.3 g/day – FILSPARI is well positioned to
become foundational care for IgAN as the treatment landscape
evolves. We are grateful to the patients, caregivers, clinical
trial investigators, healthcare providers, and advocates who have
worked alongside our team at Travere for so many years to help
raise the bar on protecting and preserving kidney health for those
living with rare kidney disease.”
FILSPARI is the only oral, once-daily,
non-immunosuppressive medication that directly targets glomerular
injury in the kidney by blocking two critical pathways of IgAN
disease progression (endothelin-1 and angiotensin II).
The two-year efficacy data contained in the
FDA-approved label is a modified intention to treat (ITT) analysis,
and as preferred by the FDA, evaluates data from all patients
regardless of treatment discontinuation. In the final analysis of
the 404 randomized patients, FILSPARI significantly reduced the
rate of decline in kidney function from baseline to Week 110
compared to irbesartan. In the ITT analysis included in the label,
the mean eGFR slope from baseline to Week 110 was -3.0 mL/min/1.73
m2/year for FILSPARI and -4.2 mL/min/1.73 m2/year for irbesartan,
corresponding to a statistically significant treatment effect of
1.2 mL/ min/1.73 m2/year (p=0.0168). The positive treatment
effects on proteinuria compared to the active control irbesartan
that were observed at Week 36 were durable out to the two-year
measurement period. Additional results from the PROTECT Study
demonstrated the benefit of FILSPARI on absolute eGFR accrued over
time and by Week 110 resulted in a 3.8 mL/min/1.73 m2 difference in
the mean change from baseline between FILSPARI and irbesartan.
Results from the PROTECT Study showed that
FILSPARI was well tolerated with a clearly defined safety profile
that has been consistent across all clinical trials conducted to
date. Following engagement with the FDA, the Company expects to
submit an sNDA for a potential modification to the liver-monitoring
REMS.
“As a physician who has dedicated my career to
treating patients with glomerular diseases, I believe the full
approval of FILSPARI for IgAN provides us with a critically
important tool for patient management,” said Brad Rovin, M.D.,
medical director at The Ohio State University Center for Clinical
Research Management, director, Division of Nephrology, and steering
committee member for the PROTECT Study. “This approval should
facilitate patient access to a medication that targets injury
directly in the kidney, reduces proteinuria, even to the point of
complete remission in some patients, and is more effective than
current standard-of-care treatment in preserving kidney function
over time. This is a very exciting milestone in the evolution of
treating IgAN.”
“Today’s full approval of FILSPARI brings new
hope to the IgAN community, and I’m grateful for the progress that
has been made in giving patients a new treatment option that can
help protect their kidneys,” said Bonnie Schneider, executive
director and co-founder of the IgA Nephropathy Foundation.
“The expanded indication and full approval of
FILSPARI is welcome news for the rare kidney disease community,”
said Josh Tarnoff, chief executive officer of NephCure. “We
have waited a long time for a medicine to slow the irreversible
kidney damage from IgAN and appreciate Travere’s leadership in
championing new endpoints for IgAN that have spurred significant
innovation for this rare kidney disease.”
Travere Therapeutics has a comprehensive
patient support program, Travere TotalCare®, to enable a smooth
experience for patients, their caregivers, and healthcare
providers. This program provides services, assistance, and
resources that can help patients understand IgAN, manage the
insurance process, fill their prescriptions and initiate
treatment. Patients or providers can call 833-FILSPARI
(833-345-7727) or visit TravereTotalCare.com to learn more.
Conference call information
Travere Therapeutics will host a conference call
and webcast today, Thursday, September 5, 2024 at 6 p.m. ET to
discuss the FDA full approval of FILSPARI. To participate in the
conference call, dial +1 (888) 394-8218 (U.S.) or +1 +1 (323)
994-2093 (International), confirmation code 1966916. The webcast
can be accessed on the Investor page of Travere’s website at
ir.travere.com/events-presentations. Following the live webcast, an
archived version of the call will be available for 30 days on the
Company’s website.
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 Phase 3 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 FILSPARI (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.
The primary efficacy endpoint for the interim
analysis was the change from baseline in urine protein/creatinine
ratio at Week 36. The key secondary efficacy endpoint for the final
analysis was the rate of change in eGFR over a 110-week period
following initiation of randomized therapy.
The trial met the pre-specified primary endpoint
which showed that after 36 weeks patients receiving FILSPARI
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 two-year efficacy data contained in the
FDA-approved label is a modified intention to treat (ITT) analysis,
and as preferred by the FDA, evaluates data from all patients
regardless of treatment discontinuation. In the final analysis of
404 randomized patients, FILSPARI reduced the rate of decline in
kidney function from baseline to Week 110 compared to irbesartan.
The mean eGFR slope from baseline to Week 110 was -3.0 mL/min/1.73
m2/year for FILSPARI and -4.2 mL/min/1.73 m2/year for irbesartan,
corresponding to a statistically significant treatment effect of
1.2 mL/ min/1.73 m2/year (p=0.0168).
Additional results from the PROTECT Study
demonstrated the benefit of FILSPARI on absolute eGFR accrued over
time and by Week 110 resulted in a 3.8 mL/min/1.73 m2 difference in
the mean change from baseline between FILSPARI and irbesartan.
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 (sparsentan) is indicated to slow
kidney function decline in adults with primary immunoglobulin A
nephropathy (IgAN) who are at risk for disease progression.
IMPORTANT SAFETY
INFORMATION
BOXED WARNING: HEPATOTOXICITY AND
EMBRYO-FETAL TOXICITY
Because 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.
Hepatotoxicity
Some 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 3.5% 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 Toxicity
FILSPARI 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 in up to 3.5% of
FILSPARI-treated patients, including cases confirmed with
rechallenge. While no concurrent elevations in bilirubin
>2-times ULN or cases of liver failure were observed in
FILSPARI-treated patients, some ERAs have caused elevations of
aminotransferases, hepatotoxicity, and liver failure. To reduce the
risk of potential serious hepatotoxicity, measure serum
aminotransferase levels and total bilirubin prior to initiation of
treatment and 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
because monitoring hepatotoxicity in these patients may be more
difficult and these patients may be at increased risk for serious
hepatotoxicity.
-
Embryo-Fetal Toxicity: FILSPARI can cause
fetal harm when administered to a pregnant patient and is
contraindicated during pregnancy. Advise patients who can become
pregnant of the potential risk to a fetus. Obtain a pregnancy test
prior to initiation of treatment with FILSPARI, monthly during
treatment, and one month after discontinuation of treatment. Advise
patients who can become pregnant to use effective contraception
prior to initiation of treatment, during treatment, and for one
month after discontinuation of treatment with FILSPARI.
- FILSPARI
REMS: Due to the risk of hepatotoxicity and
embryo-fetal toxicity, FILSPARI is available only through a
restricted program called the FILSPARI REMS. Prescribers, patients,
and pharmacies must be enrolled in the REMS program and comply with
all requirements (www.filsparirems.com).
-
Hypotension: Hypotension has been observed in
patients treated with ARBs and ERAs. 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,
despite elimination or reduction of other antihypertensive
medications, consider a dose reduction or dose interruption of
FILSPARI. A transient hypotensive response is not a
contraindication to further dosing of FILSPARI, which can be given
once blood pressure has stabilized.
-
Acute Kidney Injury: Monitor kidney function
periodically. Drugs that inhibit the renin-angiotensin system (RAS)
can cause kidney injury. Patients whose kidney function may depend
in part on the activity of the RAS (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 in clinical studies with FILSPARI. FILSPARI has
not been evaluated in patients with heart failure. If clinically
significant fluid retention develops, evaluate the patient to
determine the cause and the potential need to initiate or modify
the dose of diuretic treatment then consider modifying the dose of
FILSPARI.
Most common adverse
reactions
The most common adverse reactions (≥5%) are
hyperkalemia, hypotension (including orthostatic hypotension),
peripheral edema, dizziness, anemia, and acute kidney injury.
Drug interactions
-
Renin-Angiotensin System (RAS) Inhibitors and
ERAs: Do not coadminister FILSPARI with ARBs, ERAs,
or aliskiren due to increased risks of hypotension, syncope,
hyperkalemia, and changes in renal function (including acute renal
failure).
-
Strong and Moderate CYP3A Inhibitors: Avoid
concomitant use of FILSPARI with strong CYP3A inhibitors. If a
strong CYP3A inhibitor cannot be avoided, interrupt FILSPARI
treatment. When resuming treatment with FILSPARI, consider dose
titration. Monitor blood pressure, serum potassium, edema, and
kidney function regularly when used concomitantly with moderate
CYP3A inhibitors. Concomitant use with a strong CYP3A inhibitor
increases sparsentan exposure which may increase the risk of
FILSPARI adverse reactions.
-
Strong CYP3A Inducers: Avoid concomitant use
with a strong CYP3A inducer. Concomitant use with a strong CYP3A
inducer decreases sparsentan exposure which may reduce FILSPARI
efficacy.
-
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. Sparsentan
exhibits pH-dependent solubility. Antacids or acid reducing agents
may decrease sparsentan exposure which may reduce FILSPARI
efficacy.
-
Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including
Selective Cyclooxygenase-2 (COX-2)
Inhibitors: Monitor for signs of worsening renal
function with concomitant use with NSAIDs (including selective
COX-2 inhibitors). In patients with volume depletion (including
those on diuretic therapy) or with impaired kidney function,
concomitant use of NSAIDs (including selective COX-2 inhibitors)
with drugs that antagonize the angiotensin II receptor may result
in deterioration of kidney function, including possible kidney
failure.
-
CYP2B6, 2C9, and 2C19 Substrates: Monitor for
efficacy of concurrently administered CYP2B6, 2C9, and 2C19
substrates and consider dosage adjustment in accordance with the
Prescribing Information. Sparsentan decreases exposure of these
substrates, which may reduce efficacy related to these
substrates.
-
P-gp and BCRP Substrates: Avoid concomitant
use of sensitive substrates of P-gp and BCRP with FILSPARI.
Sparsentan may increase exposure of these transporter substrates,
which may increase the risk of adverse reactions related to these
substrates.
- Agents
Increasing Serum Potassium: Monitor serum potassium
frequently in patients treated with FILSPARI and other agents that
increase serum potassium. 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.
Please see the
full Prescribing
Information, including BOXED WARNING, for
additional Important Safety Information.
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
strategies, intentions or plans are also forward-looking
statements. Such forward-looking statements include, but are not
limited to, references to: the positioning of FILSPARI to
potentially become foundational care in IgAN and to potentially
replace the current standard of care; expectations regarding the
continuing commercial launch of FILSPARI, expectations regarding
prescribing behavior, patient access and matters related thereto;
statements regarding planned engagement with the FDA and plans to
submit an sNDA for a potential modification to the liver-monitoring
REMS; and statements relating to KDIGO guidelines. 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
its preclinical and clinical stage pipeline. Specifically, the
Company faces risks associated with the ongoing commercial launch
of FILSPARI, 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. 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 |
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/21920774-d9c9-4c88-9a02-3a33a53714e8
Travere Therapeutics (NASDAQ:TVTX)
過去 株価チャート
から 8 2024 まで 9 2024
Travere Therapeutics (NASDAQ:TVTX)
過去 株価チャート
から 9 2023 まで 9 2024