Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced the
completion of a successful pre-NDA meeting with the U.S. Food and
Drug Administration (FDA) for FILSPARI® (sparsentan) in IgA
nephropathy (IgAN). The Company will submit a supplemental New Drug
Application (sNDA) in the first quarter of 2024 for conversion of
the existing U.S. accelerated approval of FILSPARI to full
approval. The Company also completed regulatory engagement on focal
segmental glomerulosclerosis (FSGS) in which the FDA communicated
that the Phase 3 DUPLEX Study results alone are not sufficient to
support an sNDA submission for an FSGS indication for sparsentan.
As a result, the Company will be conducting additional analyses of
FSGS data with plans to re-engage FDA in 2024, and is implementing
a strategic reorganization in Q4 2023 to focus near-term resources
on the ongoing FILSPARI launch in IgAN and the advancement of
pegtibatinase in classical homocystinuria (HCU).
“Following a successful pre-NDA meeting, we are
pleased to be moving forward with our planned sNDA submission for
full approval of FILSPARI in IgA nephropathy. Our team has been
working diligently to prepare a high-quality application which we
expect to submit next quarter,” said Eric Dube, Ph.D., president
and chief executive officer of Travere Therapeutics.
“Unfortunately, there is uncertainty around a regulatory path
forward for FSGS. While we intend to continue to engage with FDA on
a way forward for the more than 40,000 people living with FSGS in
the U.S., we must at the same time prioritize our operating
expenses. As a result, we have made the difficult decision to
reduce our workforce to further focus our resources on the FILSPARI
launch and clinical development of pegtibatinase; this action is
expected to extend our cash runway into 2028. We have not taken
this decision lightly and we are grateful to all of our colleagues
who have contributed tremendously to furthering our mission and
dedication to helping people living with a rare disease. We are
committed to supporting our colleagues who are affected through
this challenging time.”
Following supportive FDA feedback on the
Company’s plan to submit the two-year results from the Phase 3
PROTECT Study in IgAN, Travere to submit sNDA in Q1 2024 for full
U.S. approval of FILSPARI in IgAN
The Company recently completed a pre-NDA meeting
with the FDA to discuss the confirmatory results from the
Phase 3 PROTECT Study and next steps for submission of an sNDA for
full approval. The FDA indicated support for the Company’s plan to
submit an sNDA for conversion from accelerated approval to full
approval and the Company is on-track to submit the sNDA in Q1
2024.
Following engagement with FDA on the
two-year results from the Phase 3 DUPLEX Study of sparsentan in
FSGS, Company conducting additional analyses of FSGS
data
The Company also completed its planned Type C
meeting with the FDA to discuss previously reported results from
the Phase 3 DUPLEX Study of sparsentan in FSGS. The FDA
acknowledged the high unmet need for approved therapies as well as
the challenges in studying FSGS but indicated that the two-year
results from the Phase 3 DUPLEX Study alone are not sufficient to
support an sNDA submission. The FDA acknowledged the work being
done by the larger nephrology community to better understand
proteinuria and eGFR as endpoints in clinical trials of FSGS and
indicated a willingness to continue to engage with the Company on a
potential path forward for sparsentan in FSGS following the
Company’s consideration of additional evidence. The Company plans
to re-engage with the FDA later in 2024.
Strategic Reorganization
To further align the Company’s resources on the
ongoing FILSPARI launch and its planned Phase 3 program advancing
the development of pegtibatinase as the first potential
disease-modifying treatment for HCU, Travere is implementing an
approximate 20% workforce reduction focused on non-field-based
employees. These adjustments are expected to result in an estimated
annualized savings of approximately $25 million beginning in 2024,
and an estimated non-recurring charge of approximately $12 million
to $14 million primarily recognized in the fourth quarter of 2023.
Alongside other cost reduction measures planned, the Company now
expects operating expenses of less than $400 million in 2024,
exclusive of cost of goods sold, depreciation and amortization and
expected net milestone payments to be made of approximately $50
million. Together with $634.6 million in cash and cash equivalents
as of September 30, 2023, the Company expects to have a cash runway
into 2028.
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. FILSPARI 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 FSGS
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 U.S. 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 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 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
percent of patients receiving sparsentan achieved FPRE, compared to
26.0 percent of irbesartan-treated patients (p=0.0094). 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. In May 2023, the Company announced topline primary
efficacy results from the DUPLEX Study of sparsentan in FSGS. The
DUPLEX Study did not achieve the primary efficacy eGFR slope
endpoint over 108 weeks of treatment. Secondary and topline
exploratory endpoints trended favorably for sparsentan. Treatment
with sparsentan resulted in a reduction of proteinuria that was
sustained through 108 weeks of treatment. Results from the two-year
analysis demonstrated that sparsentan was well-tolerated and has
shown a comparable safety profile to irbesartan. Patients who
completed the DUPLEX 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: the planned submission of an sNDA for
full approval of FILSPARI in IgAN, and the anticipated timing and
outcome thereof; planned additional analyses of FSGS data and plans
and timing for re-engaging with FDA; the potential for
pegtibatinase to be the first potential disease modifying treatment
for HCU; statements regarding the planned strategic reorganization,
the expected impact thereof, the number of employee positions that
will be impacted, and the estimated amounts and timing of the
anticipated cost savings and charges related thereto; and
expectations regarding operating expenses, milestone payments and
cash runway. 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 strategic reorganization, the
Company’s business and finances in general, 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 its planned sNDA
submission for full approval of sparsentan in IgAN, 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 the risk that its cash runway might not last
as long as currently anticipated and 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 |
Travere Therapeutics (NASDAQ:TVTX)
Gráfico Histórico do Ativo
De Mai 2024 até Jun 2024
Travere Therapeutics (NASDAQ:TVTX)
Gráfico Histórico do Ativo
De Jun 2023 até Jun 2024