Practically 60% of sufferers with IgAN within the SPARTAN Examine achieved full remission when utilizing FILSPARI as first-line therapy
SPARTACUS Examine, PROTECT open-label extension, and real-world proof displays spotlight preliminary security and efficacy knowledge of FILSPARI together therapy in IgAN
Late-breaking presentation demonstrates sparsentan delivered speedy and sustained proteinuria discount, and long-term kidney well being advantages in a subset of sufferers with genetic, usually therapy resistant, FSGS
SAN DIEGO, Oct. 26, 2024 (GLOBE NEWSWIRE) — Travere Therapeutics, Inc., (Nasdaq: TVTX), offered new knowledge additional demonstrating the scientific advantage of FILSPARI (sparsentan) in IgA nephropathy (IgAN) and reinforcing its potential in focal segmental glomerulosclerosis (FSGS) on the American Society of Nephrology (ASN) Kidney Week 2024.
The information offered at ASN offered extra proof that FILSPARI is efficient throughout all subgroups of IgAN sufferers studied to-date, and that it achieved important ranges of full remission when utilized in newly identified sufferers. We additionally shared preliminary knowledge displaying that FILSPARI safely induced additional proteinuria discount when used with SGLT2 inhibitors or steroids, supportive of the pliability for use together with different medicines as wanted, stated Jula Inrig, M.D., chief medical officer of Travere Therapeutics. Moreover, we shared knowledge exploring a subgroup of genetic FSGS sufferers in our DUPLEX Examine. Genetic FSGS sufferers are sometimes therapy resistant so the numerous reductions in proteinuria and profit on outcomes reported on this group are very encouraging.
Key Findings from the PROTECT Examine Subgroup Evaluation of Sufferers with Proteinuria Above and Under 1 g/g
- FILSPARI delivered superior proteinuria discount, and full proteinuria remission earlier and extra continuously in comparison with irbesartan no matter baseline UPCR, together with these at lower than 1.0 g/g.
Key Findings from the SPARTAN Examine Evaluating FILSPARI as a First-Line Remedy
- FILSPARI delivered a speedy and sustained discount in proteinuria of roughly 70% from baseline over 24 weeks in newly identified, RASi-naïve sufferers, and practically 60% of sufferers within the SPARTAN examine achieved full remission of proteinuria at any time limit throughout the therapy interval. All through the 24 weeks, estimated glomerular filtration price was steady.
Key Findings from the SPARTACUS Examine, PROTECT OLE and Actual-World Use Evaluating FILSPARI in Mixture Remedy for IgAN
- Interim knowledge from the SPARTACUS Examine demonstrated that FILSPARI, when added to steady SGLT2i, was usually properly tolerated. Roughly one-third of sufferers had their proteinuria decreased by no less than 50%, and two-thirds of sufferers by no less than 30% when measured after 24 weeks of therapy.
- Knowledge from the continuing PROTECT Examine open-label extension and real-world use confirmed favorable security and additive efficacy outcomes when SGLT2i or immunosuppressants have been mixed with foundational FILSPARI therapy.
Key Findings from the DUPLEX Examine Evaluating Sparsentan in Focal Segmental Glomerulosclerosis
- In a late-breaking presentation from the DUPLEX Examine in a subset of sufferers with genetic mutations in podocyte proteins, a high-risk, therapy resistant FSGS, sparsentan delivered a speedy and sustained proteinuria discount, together with some sufferers who achieved full remission and long-term kidney well being advantages.
- An evaluation of patient-reported outcomes from 306 grownup sufferers within the DUPLEX Examine confirmed that health-related high quality of life for these sufferers with FSGS on sparsentan was steady over the two-year therapy interval, and that sufferers’ burden of kidney illness was improved in comparison with these receiving irbesartan.
Key Findings from the EPPIK Examine Evaluating Sparsentan in Uncommon Proteinuric Illness in Pediatric Sufferers
- Preliminary knowledge from the EPPIK Examine confirmed that kids with a variety of uncommon proteinuric glomerular illness handled with sparsentan skilled speedy and sturdy proteinuria discount of roughly 50% over 12 weeks.
About IgA Nephropathy
IgA nephropathy (IgAN), additionally known as Berger’s illness, is a uncommon progressive kidney illness characterised by the buildup of immunoglobulin A (IgA), a protein that helps the physique combat infections, within the kidneys. The deposits of IgA trigger a breakdown of the traditional filtering mechanisms within the kidney, resulting in blood within the urine (hematuria), protein within the urine (proteinuria) and a progressive lack of kidney perform. Different signs of IgAN could embody swelling (edema) and hypertension.
IgAN is the most typical kind of major glomerulonephritis worldwide and a number one explanation for kidney failure resulting from glomerular illness. IgAN is estimated to have an effect on as much as 150,000 folks within the U.S. and is without doubt one of the most typical glomerular ailments in Europe and Japan.
About Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS) is a uncommon proteinuric kidney dysfunction in each kids and adults that’s estimated to have an effect on greater than 40,000 sufferers within the US with related prevalence in Europe. The dysfunction is outlined by progressive scarring of the kidney and sometimes results in kidney failure. FSGS is characterised by proteinuria, the place protein leaks into the urine resulting from a breakdown of the traditional filtration mechanism within the kidney. As soon as within the urine, protein is taken into account to be poisonous to different components of the kidney, particularly the tubules, and is believed to contribute to additional illness development. Different widespread signs embody swelling in components of the physique, often known as edema, in addition to low blood albumin ranges, irregular lipid profiles and hypertension. Sparsentan is just not authorised to be used in FSGS. There’s at the moment no authorised pharmacologic indicated for the therapy of FSGS.
About Travere Therapeutics
At Travere Therapeutics, we’re in uncommon for all times. We’re a biopharmaceutical firm that comes collectively day-after-day to assist sufferers, households and caregivers of all backgrounds as they navigate life with a uncommon illness. On this path, we all know the necessity for therapy choices is pressing “ that’s the reason our world staff works with the uncommon illness group to establish, develop and ship life-changing therapies. In pursuit of this mission, we constantly search to know the varied views of uncommon sufferers and to courageously forge new paths to make a distinction of their lives and supply hope “ at this time and tomorrow. For extra info, go to travere.com
FILSPARI ® (sparsentan) U.S. Indication
FILSPARI (sparsentan) is indicated to sluggish kidney perform decline in adults with major immunoglobulin A nephropathy (IgAN) who’re in danger for illness development.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY
Due to the dangers of hepatotoxicity and delivery defects, FILSPARI is on the market solely by a restricted program known as the FILSPARI REMS. Below the FILSPARI REMS, prescribers, sufferers and pharmacies should enroll in this system.
Hepatotoxicity
Some Endothelin Receptor Antagonists (ERAs) have induced elevations of aminotransferases, hepatotoxicity, and liver failure. In scientific research, elevations in aminotransferases (ALT or AST) of no less than 3-times the Higher Restrict of Regular (ULN) have been noticed in as much as 3.5% of FILSPARI-treated sufferers, together with instances confirmed with rechallenge.
Measure transaminases and bilirubin earlier than initiating therapy and month-to-month for the primary 12 months, after which each 3 months throughout therapy. Interrupt therapy and carefully monitor sufferers who develop aminotransferase elevations greater than 3x ULN.
FILSPARI ought to usually be prevented in sufferers with elevated aminotransferases (>3x ULN) at baseline as a result of monitoring for hepatotoxicity could also be tougher and these sufferers could also be at elevated threat for critical hepatotoxicity.
Embryo-Fetal Toxicity
FILSPARI may cause main delivery defects if utilized by pregnant sufferers based mostly on animal knowledge. Subsequently, being pregnant testing is required earlier than the initiation of therapy, throughout therapy and one month after discontinuation of therapy with FILSPARI. Sufferers who can turn out to be pregnant should use efficient contraception earlier than the initiation of therapy, throughout therapy, and for one month after discontinuation of therapy with FILSPARI.
Contraindications
FILSPARI is contraindicated in sufferers who’re pregnant. Don’t coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren.
Warnings and Precautions
- Hepatotoxicity: Elevations in ALT or AST of no less than 3-fold ULN have been noticed in as much as 3.5% of FILSPARI-treated sufferers, together with instances confirmed with rechallenge. Whereas no concurrent elevations in bilirubin >2-times ULN or instances of liver failure have been noticed in FILSPARI-treated sufferers, some ERAs have induced elevations of aminotransferases, hepatotoxicity, and liver failure. To scale back the danger of potential critical hepatotoxicity, measure serum aminotransferase ranges and complete bilirubin previous to initiation of therapy and month-to-month for the primary 12 months, then each 3 months throughout therapy.
Advise sufferers with signs suggesting hepatotoxicity (nausea, vomiting, proper higher quadrant ache, fatigue, anorexia, jaundice, darkish urine, fever, or itching) to instantly cease therapy with FILSPARI and search medical consideration. If aminotransferase ranges are irregular at any time throughout therapy, interrupt FILSPARI and monitor as beneficial.
Take into account re-initiation of FILSPARI solely when hepatic enzyme ranges and bilirubin return to pretreatment values and solely in sufferers who haven’t skilled scientific signs of hepatotoxicity. Keep away from initiation of FILSPARI in sufferers with elevated aminotransferases (>3x ULN) previous to drug initiation as a result of monitoring hepatotoxicity in these sufferers could also be tougher and these sufferers could also be at elevated threat for critical hepatotoxicity.
- Embryo-Fetal Toxicity: FILSPARI may cause fetal hurt when administered to a pregnant affected person and is contraindicated throughout being pregnant. Advise sufferers who can turn out to be pregnant of the potential threat to a fetus. Acquire a being pregnant check previous to initiation of therapy with FILSPARI, month-to-month throughout therapy, and one month after discontinuation of therapy. Advise sufferers who can turn out to be pregnant to make use of efficient contraception previous to initiation of therapy, throughout therapy, and for one month after discontinuation of therapy with FILSPARI.
- FILSPARI REMS: Because of the threat of hepatotoxicity and embryo-fetal toxicity, FILSPARI is on the market solely by a restricted program known as the FILSPARI REMS. Prescribers, sufferers, and pharmacies should be enrolled within the REMS program and adjust to all necessities (www.filsparirems.com).
- Hypotension: Hypotension has been noticed in sufferers handled with ARBs and ERAs. There was a larger incidence of hypotension-associated hostile occasions, some critical, together with dizziness, in sufferers handled with FILSPARI in comparison with irbesartan. In sufferers in danger for hypotension, think about eliminating or adjusting different antihypertensive drugs and sustaining acceptable quantity standing. If hypotension develops, regardless of elimination or discount of different antihypertensive drugs, think about a dose discount or dose interruption of FILSPARI. A transient hypotensive response is just not a contraindication to additional dosing of FILSPARI, which will be given as soon as blood stress has stabilized.
- Acute Kidney Harm: Monitor kidney perform periodically. Medication that inhibit the renin-angiotensin system (RAS) may cause kidney damage. Sufferers whose kidney perform could rely partially on the exercise of the RAS (e.g., sufferers with renal artery stenosis, power kidney illness, extreme congestive coronary heart failure, or quantity depletion) could also be at specific threat of growing acute kidney damage on FILSPARI. Take into account withholding or discontinuing remedy in sufferers who develop a clinically important lower in kidney perform whereas on FILSPARI.
- Hyperkalemia: Monitor serum potassium periodically and deal with appropriately. Sufferers with superior kidney illness, taking concomitant potassium-increasing medication (e.g., potassium dietary supplements, potassium-sparing diuretics), or utilizing potassium-containing salt substitutes are at elevated threat for growing hyperkalemia. Dosage discount or discontinuation of FILSPARI could also be required.
- Fluid Retention: Fluid retention could happen with ERAs, and has been noticed in scientific research with FILSPARI. FILSPARI has not been evaluated in sufferers with coronary heart failure. If clinically important fluid retention develops, consider the affected person to find out the trigger and the potential have to provoke or modify the dose of diuretic therapy then think about modifying the dose of FILSPARI.
Most typical hostile reactions
The most typical hostile reactions ( ‰¥5%) are hyperkalemia, hypotension (together with orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney damage.
Drug interactions
- Renin-Angiotensin System (RAS) Inhibitors and ERAs: Don’t coadminister FILSPARI with ARBs, ERAs, or aliskiren resulting from elevated dangers of hypotension, syncope, hyperkalemia, and adjustments in renal perform (together with acute renal failure).
- Robust and Reasonable CYP3A Inhibitors: Keep away from concomitant use of FILSPARI with sturdy CYP3A inhibitors. If a robust CYP3A inhibitor can’t be prevented, interrupt FILSPARI therapy. When resuming therapy with FILSPARI, think about dose titration. Monitor blood stress, serum potassium, edema, and kidney perform commonly when used concomitantly with average CYP3A inhibitors. Concomitant use with a robust CYP3A inhibitor will increase sparsentan publicity which can improve the danger of FILSPARI hostile reactions.
- Robust CYP3A Inducers: Keep away from concomitant use with a robust CYP3A inducer. Concomitant use with a robust CYP3A inducer decreases sparsentan publicity which can scale back FILSPARI efficacy.
- Antacids and Acid Decreasing Brokers: Administer FILSPARI 2 hours earlier than or after administration of antacids. Keep away from concomitant use of acid decreasing brokers (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Sparsentan displays pH-dependent solubility. Antacids or acid decreasing brokers could lower sparsentan publicity which can scale back FILSPARI efficacy.
- Non-Steroidal Anti-Inflammatory Brokers (NSAIDs), Together with Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for indicators of worsening renal perform with concomitant use with NSAIDs (together with selective COX-2 inhibitors). In sufferers with quantity depletion (together with these on diuretic remedy) or with impaired kidney perform, concomitant use of NSAIDs (together with selective COX-2 inhibitors) with medication that antagonize the angiotensin II receptor could lead to deterioration of kidney perform, together with attainable kidney failure.
- CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and think about dosage adjustment in accordance with the Prescribing Data. Sparsentan decreases publicity of those substrates, which can scale back efficacy associated to those substrates.
- P-gp and BCRP Substrates: Keep away from concomitant use of delicate substrates of P-gp and BCRP with FILSPARI. Sparsentan could improve publicity of those transporter substrates, which can improve the danger of hostile reactions associated to those substrates.
- Brokers Growing Serum Potassium: Monitor serum potassium continuously in sufferers handled with FILSPARI and different brokers that improve serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium dietary supplements, potassium-containing salt substitutes, or different medication that elevate serum potassium ranges could lead to hyperkalemia.
Please see the total Prescribing Data, together with BOXED WARNING, for extra Vital Security Data.
Ahead Trying Statements
This press launch comprises forward-looking statements as that time period is outlined within the Non-public Securities Litigation Reform Act of 1995. With out limiting the foregoing, these statements are sometimes recognized by the phrases on-track, positioned, sit up for, will, would, could, may, believes, anticipates, plans, expects, intends, potential, or related expressions. As well as, expressions of methods, intentions or plans are additionally forward-looking statements. Such forward-looking statements embody, however aren’t restricted to, references to: assertion associated to the potential for FILSPARI for use as a first-line therapy for IgAN and the pliability of FILSPARI for use together with different medicines; statements regarding scientific research, together with however not restricted to trial design, outcomes and timing associated thereto; and prevalence estimates. Such forward-looking statements are based mostly on present expectations and contain inherent dangers and uncertainties, together with components that might delay, divert or change any of them, and will trigger precise outcomes and outcomes to vary materially from present expectations. No forward-looking assertion will be assured. Among the many components that might trigger precise outcomes to vary materially from these indicated within the forward-looking statements are dangers associated to the timing and end result of the research described herein and uncertainties related to the regulatory evaluation and approval course of, in addition to dangers and uncertainties related to enrollment of scientific trials for uncommon ailments, and dangers that ongoing or deliberate scientific trials could not succeed or could also be delayed for security, regulatory or different causes. The Firm additionally faces dangers associated to its enterprise and funds on the whole, the success of its business merchandise and dangers and uncertainties related to its preclinical and scientific stage pipeline. Particularly, the Firm faces dangers related to the continuing business launch of FILSPARI, market acceptance of its business merchandise together with efficacy, security, value, reimbursement, and profit over competing therapies, in addition to dangers related to the profitable improvement and execution of business methods for such merchandise, together with FILSPARI. The dangers and uncertainties the Firm faces with respect to its preclinical and scientific stage pipeline embody threat that the Firm’s scientific candidates is not going to be discovered to be protected or efficient and that present or anticipated future scientific trials is not going to proceed as deliberate. There isn’t any assure that regulators will grant approval of sparsentan for FSGS. The Firm additionally faces the danger that it will likely be unable to lift extra funding that could be required to finish improvement of all or any of its product candidates, together with because of macroeconomic situations; dangers regarding the Firm’s dependence on contractors for scientific drug provide and business manufacturing; uncertainties regarding patent safety and exclusivity intervals and mental property rights of third events; dangers related to regulatory interactions; and dangers and uncertainties regarding aggressive merchandise, together with present and potential future generic competitors with sure of the Firm’s merchandise, and technological adjustments which will restrict demand for the Firm’s merchandise. The Firm additionally faces extra dangers related to world and macroeconomic situations, together with well being epidemics and pandemics, together with dangers associated to potential disruptions to scientific trials, commercialization exercise, provide chain, and manufacturing operations. You’re cautioned to not place undue reliance on these forward-looking statements as there are essential components that might trigger precise outcomes to vary materially from these in forward-looking statements, lots of that are past our management. The Firm undertakes no obligation to publicly replace any forward-looking assertion, whether or not because of new info, future occasions, or in any other case. Traders are referred to the total dialogue of dangers and uncertainties, together with beneath the heading Threat Elements, as included within the Firm’s most up-to-date Type 10-Ok, Type 10-Q and different filings with the Securities and Trade Fee.
Contact Information
| Media: 888-969-7879 mediarelations@travere.com |
Traders: 888-969-7879 IR@travere.com |
