Upgrade Your Adult Patients’ IgAN Treatment

Transcript

This is a transcript of an educational program sponsored by Travere Therapeutics.

FILSPARI^® (sparsentan) is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. Please see the full Prescribing Information, including BOXED WARNING, for additional Important Safety Information.

ReachMD Announcer:
You’re listening to ReachMD. This medical industry feature, titled “Upgrade Your Adult Patients' IgAN Treatment” is sponsored by Travere Therapeutics.

This presentation is intended for US healthcare professionals only. Please listen to the entire program for indication and important safety information including boxed warnings for FILSPARI also known as sparsentan. Full prescribing information can be found at www.filsparihcp.com.

And now, here are Dr.'s Omaima Degani and Abdul Abdellatif. 

Dr. Degani:
My name is Omaima Degani. I'm a community based nephrologist in the Chicago area. I see the whole gamut of nephrology patients, including IgA Nephropathy. 

Dr. Abdellatif:
My name is Dr. Abdul Abdullatif. I'm a joint assistant professor of medicine at Baylor College of Medicine. I'm also the chief of nephrology at CLS health in the Houston area. I see a broad range of patients with chronic kidney disease, including patients with glomerular diseases.

Dr. Degani:
So for many years, we've really only had one treatment option, that's RAS inhibition, either ACE or ARB. I have been using ACE and ARB because that is the standard of care, but I feel at this time that we really need to find better ways to treat our patients. 

How are you currently setting proteinuria goals for your patients? Do you feel the treatments we have currently reach those goals?

Dr. Abdellatif:
Currently, when I treat my patients with IgA nephropathy, I always wanted to target the recommended guidelines goal of less than one gram, but I noticed that the patient's disease stayed still active and progressing even at that level. 

Dr. Degani:
I think that we do our best and we treat our patients with RAS inhibition, but most patients do not, unfortunately, achieve what we want them to achieve…And I think recently we have a study, the RaDaR study from the UK, that has shown that we really should be using lower proteinuria goals than we have been, especially in the younger patients.

Are you aware of that trial?

Dr. Abdellatif:
Yeah, actually it's very interesting…Actually, what they noticed, that even at lower levels of proteinuria, even less than a gram, these young patients who were in their thirties or even their twenties, were having end-stage renal disease within 10 years of their diagnosis.

Dr. Degani:
So, you know, for me at least these results were very surprising. You know, as a community nephrologist, we always try to treat patients to about a gram of proteinuria and we feel very comfortable thinking that patients will not progress. But this recent data does tell us that we need to be more aggressive with our patients and…treating to a lower level. Because as we know, time is nephrons.

So, Dr. Abdellatif, the IgA nephropathy treatment landscape has changed in the past several years with the availability of new treatment options and new mechanisms of action, which we've never had before.

Dr. Abdellatif:
Actually, I'm glad that 30 years after the birth of RAS blockade, now we have other options for our patients. We know that we can target different pathways...either at the cellular level or directly at the kidney level.

Dr. Degani:
Yeah, I totally agree. It's actually a very exciting time to be a nephrologist. Having all these treatment options available.

How do you define a therapy as foundational standard of care for IgA nephropathy?

Dr. Abdellatif:
A foundational therapy is a therapy that works directly in the kidney and targets...glomerular damage, with no immunosuppression, achieving better proteinuria reduction than what we currently have with RAS inhibition, but also need to have a favorable safety profile to allow for long-term use, and finally… can be used in a wide range of patients.

Dr. Degani:
Well, FILSPARI is the first and only single molecule that touches both the endothelin-1 and angiotensin II pathways. Our current standard of care, RAS inhibition, only touches the angiotensin II.

I think FILSPARI is definitely an upgrade to traditional standard of care with RAS inhibition.

In fact, the PROTECT trial was specifically designed to demonstrate that.

In the PROTECT trial, FILSPARI offered superior, rapid, and sustained proteinuria reduction compared…head-to-head…against a maximum labeled dose of irbesartan.

Dr. Abdellatif:
The efficacy results from the PROTECT trial, it's actually outstanding. We saw that using FILSPARI has a greater reduction in proteinuria that was early and sustained.

What do you think about the safety profile of FILSPARI?

Dr. Degani:
So I certainly think we can be reassured with the data that FILSPARI can be well tolerated by our patients.

There were no severe cases of edema or associated discontinuation for patients on FILSPARI in the study. Although some cases of elevated LFTs were found in the study, there was no drug-induced liver injury following treatment with FILSPARI.

Dr. Abdellatif:
That's very assuring, because as we discussed earlier about a foundational therapy, that we need something that we can use for our patients for a long period of time with a favorable safety profile.

Voiceover:
The most common adverse reactions (≥5%) are peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia.

Dr. Degani:
What kinds of results have you observed with your patients on FILSPARI?

Dr. Abdellatif:
I have seen positive results in my patients on FILSPARI…In one patient who had actually been treated with multiple other medications with a baseline therapy of RAS blockade, as soon as I switched him from RAS blockade to FILSPARI, within four weeks, I saw about 50% reduction in proteinuria, and on follow-up visits, that proteinuria reduction was completely sustained while staying on the medication.

Dr. Degani:
FILSPARI really does…seem to be the optimal treatment in our patients with IgA nephropathy.

Dr. Abdellatif:
Dr. Degani, how are you currently integrating FILSPARI in your clinical practice?

Dr. Degani:
In my clinical practice, I am using FILSPARI as a first-line agent. Patients typically come to me on ACE or ARB already, and I am stopping that medication, starting FILSPARI in the appropriate IgA nephropathy patients, in the hopes of reducing their proteinuria and slowing their disease progression.

Dr. Abdellatif:
If you could describe FILSPARI in one word...what would it be?

Dr. Degani:
So if I had to describe FILSPARI in one word, I would describe it as essential. I do feel it is an essential part of the treatment paradigm for IgA nephropathy.

Dr. Abdellatif:
To me, as a practicing nephrologist, we can definitely think of FILSPARI as the upgraded standard of care for patients with IgA nephropathy.

Voiceover:
INDICATIONS AND USAGE
FILSPARI^® (sparsentan) is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.

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.

HEPATOTOXITICTY
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.