Practically 60% of sufferers with IgAN within the SPARTAN Research achieved full remission when utilizing FILSPARI as first-line remedy
SPARTACUS Research, PROTECT open-label extension, and real-world proof shows spotlight preliminary security and efficacy information of FILSPARI together remedy in IgAN
Late-breaking presentation demonstrates sparsentan delivered fast and sustained proteinuria discount, and long-term kidney well being advantages in a subset of sufferers with genetic, typically remedy resistant, FSGS
SAN DIEGO, Oct. 26, 2024 (GLOBE NEWSWIRE) — Travere Therapeutics, Inc., (Nasdaq: TVTX), offered new information additional demonstrating the medical good thing about 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 info offered at ASN offered further proof that FILSPARI is efficient throughout all subgroups of IgAN sufferers studied to-date, and that it achieved vital ranges of full remission when utilized in newly identified sufferers. We additionally shared preliminary information exhibiting that FILSPARI safely induced additional proteinuria discount when used with SGLT2 inhibitors or steroids, supportive of the flexibleness for use together with different medicines as wanted, mentioned Jula Inrig, M.D., chief medical officer of Travere Therapeutics. Moreover, we shared information exploring a subgroup of genetic FSGS sufferers in our DUPLEX Research. Genetic FSGS sufferers are sometimes remedy resistant so the numerous reductions in proteinuria and profit on outcomes reported on this group are very encouraging.
Key Findings from the PROTECT Research Subgroup Evaluation of Sufferers with Proteinuria Above and Beneath 1 g/g
- FILSPARI delivered superior proteinuria discount, and full proteinuria remission earlier and extra often in comparison with irbesartan no matter baseline UPCR, together with these at lower than 1.0 g/g.
Key Findings from the SPARTAN Research Evaluating FILSPARI as a First-Line Remedy
- FILSPARI delivered a fast and sustained discount in proteinuria of roughly 70% from baseline over 24 weeks in newly identified, RASi-naïve sufferers, and almost 60% of sufferers within the SPARTAN research achieved full remission of proteinuria at any cut-off date throughout the remedy interval. All through the 24 weeks, estimated glomerular filtration fee was steady.
Key Findings from the SPARTACUS Research, PROTECT OLE and Actual-World Use Evaluating FILSPARI in Mixture Remedy for IgAN
- Interim information from the SPARTACUS Research demonstrated that FILSPARI, when added to steady SGLT2i, was typically nicely tolerated. Roughly one-third of sufferers had their proteinuria lowered by a minimum of 50%, and two-thirds of sufferers by a minimum of 30% when measured after 24 weeks of remedy.
- Knowledge from the continuing PROTECT Research open-label extension and real-world use confirmed favorable security and additive efficacy outcomes when SGLT2i or immunosuppressants had been mixed with foundational FILSPARI remedy.
Key Findings from the DUPLEX Research Evaluating Sparsentan in Focal Segmental Glomerulosclerosis
- In a late-breaking presentation from the DUPLEX Research in a subset of sufferers with genetic mutations in podocyte proteins, a high-risk, remedy resistant FSGS, sparsentan delivered a fast 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 Research confirmed that health-related high quality of life for these sufferers with FSGS on sparsentan was steady over the two-year remedy interval, and that sufferers’ burden of kidney illness was improved in comparison with these receiving irbesartan.
Key Findings from the EPPIK Research Evaluating Sparsentan in Uncommon Proteinuric Illness in Pediatric Sufferers
- Preliminary information from the EPPIK Research confirmed that kids with a variety of uncommon proteinuric glomerular illness handled with sparsentan skilled fast and strong proteinuria discount of roughly 50% over 12 weeks.
About IgA Nephropathy
IgA nephropathy (IgAN), additionally referred to 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 conventional filtering mechanisms within the kidney, resulting in blood within the urine (hematuria), protein within the urine (proteinuria) and a progressive lack of kidney operate. Different signs of IgAN could embody swelling (edema) and hypertension.
IgAN is the commonest kind of main glomerulonephritis worldwide and a number one explanation for kidney failure as a result of glomerular illness. IgAN is estimated to have an effect on as much as 150,000 individuals within the U.S. and is among the commonest 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 infrequently results in kidney failure. FSGS is characterised by proteinuria, the place protein leaks into the urine as a result of a breakdown of the conventional filtration mechanism within the kidney. As soon as within the urine, protein is taken into account to be poisonous to different elements of the kidney, particularly the tubules, and is believed to contribute to additional illness development. Different frequent signs embody swelling in elements of the physique, generally known as edema, in addition to low blood albumin ranges, irregular lipid profiles and hypertension. Sparsentan isn’t accredited to be used in FSGS. There’s presently no accredited pharmacologic indicated for the remedy of FSGS.
About Travere Therapeutics
At Travere Therapeutics, we’re in uncommon for all times. We’re a biopharmaceutical firm that comes collectively every single 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 remedy choices is pressing “ that’s the reason our world staff works with the uncommon illness neighborhood to establish, develop and ship life-changing therapies. In pursuit of this mission, we constantly search to grasp the various views of uncommon sufferers and to courageously forge new paths to make a distinction of their lives and supply hope “ at the moment and tomorrow. For extra info, go to travere.com
FILSPARI ® (sparsentan) U.S. Indication
FILSPARI (sparsentan) is indicated to gradual kidney operate decline in adults with main 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 accessible solely by a restricted program referred to as the FILSPARI REMS. Beneath the FILSPARI REMS, prescribers, sufferers and pharmacies should enroll in this system.
Hepatotoxicity
Some Endothelin Receptor Antagonists (ERAs) have prompted elevations of aminotransferases, hepatotoxicity, and liver failure. In medical research, elevations in aminotransferases (ALT or AST) of a minimum of 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 remedy and month-to-month for the primary 12 months, after which each 3 months throughout remedy. Interrupt remedy and intently monitor sufferers who develop aminotransferase elevations greater than 3x ULN.
FILSPARI ought to typically be prevented in sufferers with elevated aminotransferases (>3x ULN) at baseline as a result of monitoring for hepatotoxicity could also be harder and these sufferers could also be at elevated danger for severe hepatotoxicity.
Embryo-Fetal Toxicity
FILSPARI may cause main delivery defects if utilized by pregnant sufferers based mostly on animal information. Due to this fact, being pregnant testing is required earlier than the initiation of remedy, throughout remedy and one month after discontinuation of remedy with FILSPARI. Sufferers who can change into pregnant should use efficient contraception earlier than the initiation of remedy, throughout remedy, and for one month after discontinuation of remedy 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 a minimum of 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 had been noticed in FILSPARI-treated sufferers, some ERAs have prompted elevations of aminotransferases, hepatotoxicity, and liver failure. To cut back the chance of potential severe hepatotoxicity, measure serum aminotransferase ranges and complete bilirubin previous to initiation of remedy and month-to-month for the primary 12 months, then each 3 months throughout remedy.
Advise sufferers with signs suggesting hepatotoxicity (nausea, vomiting, proper higher quadrant ache, fatigue, anorexia, jaundice, darkish urine, fever, or itching) to instantly cease remedy with FILSPARI and search medical consideration. If aminotransferase ranges are irregular at any time throughout remedy, interrupt FILSPARI and monitor as really helpful.
Contemplate re-initiation of FILSPARI solely when hepatic enzyme ranges and bilirubin return to pretreatment values and solely in sufferers who haven’t skilled medical 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 harder and these sufferers could also be at elevated danger for severe 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 change into pregnant of the potential danger to a fetus. Get hold of a being pregnant check previous to initiation of remedy with FILSPARI, month-to-month throughout remedy, and one month after discontinuation of remedy. Advise sufferers who can change into pregnant to make use of efficient contraception previous to initiation of remedy, throughout remedy, and for one month after discontinuation of remedy with FILSPARI.
- FILSPARI REMS: As a result of danger of hepatotoxicity and embryo-fetal toxicity, FILSPARI is accessible solely by a restricted program referred to as the FILSPARI REMS. Prescribers, sufferers, and pharmacies have to 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 better incidence of hypotension-associated hostile occasions, some severe, together with dizziness, in sufferers handled with FILSPARI in comparison with irbesartan. In sufferers in danger for hypotension, take into account eliminating or adjusting different antihypertensive drugs and sustaining applicable quantity standing. If hypotension develops, regardless of elimination or discount of different antihypertensive drugs, take into account a dose discount or dose interruption of FILSPARI. A transient hypotensive response isn’t a contraindication to additional dosing of FILSPARI, which could be given as soon as blood strain has stabilized.
- Acute Kidney Harm: Monitor kidney operate periodically. Medication that inhibit the renin-angiotensin system (RAS) may cause kidney damage. Sufferers whose kidney operate could rely partially on the exercise of the RAS (e.g., sufferers with renal artery stenosis, persistent kidney illness, extreme congestive coronary heart failure, or quantity depletion) could also be at specific danger of creating acute kidney damage on FILSPARI. Contemplate withholding or discontinuing remedy in sufferers who develop a clinically vital lower in kidney operate whereas on FILSPARI.
- Hyperkalemia: Monitor serum potassium periodically and deal with appropriately. Sufferers with superior kidney illness, taking concomitant potassium-increasing medicine (e.g., potassium dietary supplements, potassium-sparing diuretics), or utilizing potassium-containing salt substitutes are at elevated danger for creating hyperkalemia. Dosage discount or discontinuation of FILSPARI could also be required.
- Fluid Retention: Fluid retention could happen with ERAs, and has been noticed in medical research with FILSPARI. FILSPARI has not been evaluated in sufferers with coronary heart failure. If clinically vital fluid retention develops, consider the affected person to find out the trigger and the potential must provoke or modify the dose of diuretic remedy then take into account modifying the dose of FILSPARI.
Commonest 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 as a result of elevated dangers of hypotension, syncope, hyperkalemia, and adjustments in renal operate (together with acute renal failure).
- Sturdy and Reasonable CYP3A Inhibitors: Keep away from concomitant use of FILSPARI with robust CYP3A inhibitors. If a powerful CYP3A inhibitor can’t be prevented, interrupt FILSPARI remedy. When resuming remedy with FILSPARI, take into account dose titration. Monitor blood strain, serum potassium, edema, and kidney operate recurrently when used concomitantly with reasonable CYP3A inhibitors. Concomitant use with a powerful CYP3A inhibitor will increase sparsentan publicity which can improve the chance of FILSPARI hostile reactions.
- Sturdy CYP3A Inducers: Keep away from concomitant use with a powerful CYP3A inducer. Concomitant use with a powerful CYP3A inducer decreases sparsentan publicity which can cut back FILSPARI efficacy.
- Antacids and Acid Lowering Brokers: Administer FILSPARI 2 hours earlier than or after administration of antacids. Keep away from concomitant use of acid lowering brokers (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Sparsentan reveals pH-dependent solubility. Antacids or acid lowering brokers could lower sparsentan publicity which can cut back FILSPARI efficacy.
- Non-Steroidal Anti-Inflammatory Brokers (NSAIDs), Together with Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for indicators of worsening renal operate 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 operate, concomitant use of NSAIDs (together with selective COX-2 inhibitors) with medicine that antagonize the angiotensin II receptor could lead to deterioration of kidney operate, together with attainable kidney failure.
- CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and take into account dosage adjustment in accordance with the Prescribing Data. Sparsentan decreases publicity of those substrates, which can cut 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 chance of hostile reactions associated to those substrates.
- Brokers Growing Serum Potassium: Monitor serum potassium often 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 medicine that elevate serum potassium ranges could lead to hyperkalemia.
Please see the complete Prescribing Data, together with BOXED WARNING, for extra Necessary Security Data.
Ahead Trying Statements
This press launch comprises forward-looking statements as that time period is outlined within the Personal 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 remedy for IgAN and the flexibleness of FILSPARI for use together with different medicines; statements regarding medical 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 could 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 assessment and approval course of, in addition to dangers and uncertainties related to enrollment of medical trials for uncommon ailments, and dangers that ongoing or deliberate medical 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 typically, the success of its industrial merchandise and dangers and uncertainties related to its preclinical and medical stage pipeline. Particularly, the Firm faces dangers related to the continuing industrial launch of FILSPARI, market acceptance of its industrial merchandise together with efficacy, security, worth, 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 medical stage pipeline embody danger that the Firm’s medical candidates won’t be discovered to be protected or efficient and that present or anticipated future medical trials won’t proceed as deliberate. There isn’t a assure that regulators will grant approval of sparsentan for FSGS. The Firm additionally faces the chance that it will likely be unable to lift further funding which may be required to finish improvement of all or any of its product candidates, together with on account of macroeconomic situations; dangers regarding the Firm’s dependence on contractors for medical drug provide and industrial manufacturing; uncertainties regarding patent safety and exclusivity durations 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 that will restrict demand for the Firm’s merchandise. The Firm additionally faces further dangers related to world and macroeconomic situations, together with well being epidemics and pandemics, together with dangers associated to potential disruptions to medical trials, commercialization exercise, provide chain, and manufacturing operations. You might be 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, a lot of that are past our management. The Firm undertakes no obligation to publicly replace any forward-looking assertion, whether or not on account of new info, future occasions, or in any other case. Buyers are referred to the complete dialogue of dangers and uncertainties, together with underneath the heading Threat Components, as included within the Firm’s most up-to-date Type 10-Ok, Type 10-Q and different filings with the Securities and Alternate Fee.
Contact Data
| Media: 888-969-7879 mediarelations@travere.com |
Buyers: 888-969-7879 IR@travere.com |
