Travere Therapeutics has recently launched their Phase 2 pediatric clinical trial, EPPIK (Evaluating Problematic Proteinuria in Kids) which is aimed at helping children with FSGS, MCD, IgAN and other rare kidney diseases. We know that with a clinical study specifically designed for kids, parents and caregivers may have some questions. We asked Travere to answer some of these questions and have complied an FAQ list for our community around EPPIK.

1. What is the EPPIK study?
   • EPPIK (Evaluating Problematic Proteinuria in Kids) is a Phase 2 study of children 1-17 years old with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), IgA nephropathy (IgAN), also known as Berger’s disease, IgA vasculitis (IgAV), also known as Henoch-Schönlein purpura, or Alport syndrome (AS). These rare kidney diseases are associated with progression to end-stage kidney disease and currently have limited or no treatment options. This study aims to further understand if an investigational therapy, sparsentan, can help the kidneys filter protein and slow the decline of kidney function.  The amount of protein found in the urine (called proteinuria) is seen as a marker of kidney function. Lowering proteinuria levels is associated with better kidney health outcomes.
2. What is sparsentan?
   • Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) – this means it is a dual acting, highly selective antagonist of both the endothelin A receptor (ETAR) and the angiotensin II subtype 1 receptor (AT1R).
   • In the EPPIK Study, sparsentan is taken once a day orally.
3. What is a Phase 2 study?
   • A Phase 2 study is a clinical trial that helps researchers determine how safe, tolerable and effective an investigational drug may be in specific patient populations, such as those noted above. While the EPPIK study is a Phase 2 study, sparsentan has been studied in another Phase 2 study as well as two Phase 3 studies involving approximately 880 patients (some of whom were children). The purpose of the EPPIK study is to gain further experience on the use of sparsentan in children.
4. How long does this study take?
   • Patients who meet all eligibility criteria and are enrolled in the study may expect to participate in the study for about 2 years and 3 months.
5. Will you be enrolling children with congenital Nephrotic Syndrome or infantile Nephrotic Syndrome?
   • Yes, children ages 1-17 with one of those syndromes who meet the study criteria will be able to participate in the EPPIK Study. The specific disorders we are looking for are noted above in the answer to question 1.
6. How many children and young people are you looking to enroll in this study?
   • We will be looking to enroll approximately 57 children in the EPPIK study.
7. How many study sites are there available? Where are these sites located?
   • Sites will be in the United States, UK, and various countries in the EU (France, Germany, Italy, Spain, Netherlands, Poland, Sweden). The final list of sites has not been fully determined yet.
8. Because this study is for children, how is it different than a study for adults?
   • The main difference is how much blood is drawn from the children to do all the tests necessary to evaluate sparsentan in the study. Patient safety is always our number one priority, and, with children, we won’t sample as much blood as we would from an adult. We narrowed the number of tests and worked with the central lab to be able to get results from a smaller sample size. We also must ensure that we adequately inform both the child who might participate in the study and the child’s parents/guardians about all the requirements the study has as well as any risks that may be associated with participating in the study. We do this by developing different study assents or ways to communicate what the study entails so that participating families understand the purpose of the study and what is involved.
9. Are you asking kids about the taste, smell, etc. of the study drug?
   • Yes, we will be asking the children to answer simple questions on how the drug tastes, smells, feels, etc.
10. How do you determine which participants will be required to have pregnancy testing or take birth control?
    • We realize this is a delicate subject for some children and their parents, but it is very important that any female child who has had her first menstruation period take birth control according to the protocol. This class of drugs is known to potentially cause harm to a developing fetus, and therefore we do not want any female participant who is able to have a child to become pregnant.
11. Is there flexibility where lab samples can be collected for my child? Is there an option for home care visits to collect these samples?
    • Yes, there is some flexibility in where labs are taken. If the child can’t make it to the clinical site to have the labs drawn, which is always the preferred way, we have contracted with a company that will come to the patient’s home or other convenient location, to draw the labs and send them in for testing.
12. Does my child have to stop the medications they’re on? What drugs can they remain on?
    • That depends, if they are enrolled in this study, they will need to stop any drug that functions similarly to the investigational drug. That is, if they are on an ACE inhibitor or ARB, they will need to stop those drugs at least 2 weeks before they begin taking the experimental drug and will not be able to take them while they are participating in the study. They will be able to continue with certain blood pressure medications if not in the same drug class, as well as many other medications they may be on. The Investigator will have a complete list of drugs that are allowed and not allowed.
13. What will happen to the results of this clinical study?
    • After all the patients have been enrolled and have completed the study, the data will be analyzed to see if it was successful in reducing the amount of protein in the urine and if it slowed the decline in kidney function as measured by estimated glomerular filtration rate, or eGFR. How well the drug was tolerated, that is, the safety profile, will also be analyzed. Those results will, in all likelihood, be put into a document known as a manuscript and published in a scientific journal. Data will also be added to the study listing on the clinicaltrials.gov website at the end of the study.
14. If my child is in another trial studying sparsentan, do they have to enroll in this new study? If so, will their study site change? 
    • No, if your child is participating in another trial with sparsentan they would not be eligible to join the EPPIK study. They would stay in the study they are currently in.

For more information about EPPIK, contact medinfo@travere.com

Kaneka’s LIPOSORBER® LA-15 System is a blood processing machine used outside of the body. This LDL apheresis device removes certain lipoproteins (cholesterol) from the blood. It’s used for pediatric and adult patients diagnosed with primary Focal Segmental Glomerulosclerosis (FSGS) either before transplant or who experienced FSGS recurrence after transplant.

Several doctors across the country have been treating patients with the LIPOSORBER®, including Dr. Joshua Zaritsky, a pediatric nephrologist, and Dr. Vasil Peev, an adult nephrologist. We asked both doctors to share their experience with the LIPOSORBER® system and recommendations for patients considering this treatment option.

What is your experience with LDL apheresis, and what kind of patients do you treat?

ZARITSKY: I’ve had experience with LDL apheresis over the last six years. There are two classes of patients I treat. One is patients who have had a renal transplant and have had recurrence — they’re probably the most common patients I treat. The other group of patients are those who have FSGS or another sort of steroid-resistant nephrotic syndrome. Those patients haven’t yet undergone transplantation.

PEEV: I’ve treated two patients so far with LDL apheresis who have had recurrent FSGS and are post-transplant.

What has the patient’s response been to the treatment?

ZARITSKY: I’ve had very good luck with those patients who have had recurrence after transplant. We actually published that data; we had seven back-to-back cases that were 100% successful. Since then, we’ve had some failures to treatment, but we’ve had very good luck post-transplant. In the pre-transplant area, we see response rates anywhere from 30-50%. But that being said, we’ve had some incredible responses. Other centers were about to take out both patients’ kidneys, and we’ve been able to rescue them and put them into remission.

PEEV: Both patients have had an outstanding response to LDL apheresis. One of them had recurrenceafter receiving a living-donor kidney from his mother. He’s now almost three years post-transplant with very stable renal function and no proteinuria. I just saw this patient recently and he’s doing fantastic! His kidney function remains somewhat impaired as his LDL apheresis treatment was initially delayed leading to some progression of CKD from recurrent FSGS after his transplant. When treating him after transplant, I initially gave him what is considered to be standard of care, i.e. plasmapheresis (and various other medications). He unfortunately failed these despite very aggressive and numerous efforts to control his proteinuria. The LDL apheresis was basically a Hail Mary treatment that really saved his kidney and kept him off dialysis.

Are patients comfortable during the treatment?

ZARITSKY: What I’ve noticed as a doctor is that this is very well-tolerated treatment. There’s not a lot of side effects. For the most part in my clinical experience, there hasn’t been a lot of side effects.

PEEV: From what I’ve heard patients say, it’s very comfortable and much smoother than dialysis treatment. The blood flows are much lower (50-100 CCs per hour). The treatments last for few hours and are very well tolerated. Patients don’t feel drained, which is something that’s frequently described with dialysis.

What is your recommendation for other nephrologists?

ZARITSKY: I think it’s important to reach out to other physicians who have some experience using the equipment, because we can also put our nurses in touch with their nurses who have experience. There’s some tricks and tips that we’re willing to share and, for the most part, it’s a nice community of doctors who are always willing to help out.

PEEV: I think that it’s definitely worth a try. Again, in the field of nephrology, unfortunately, we still are working with a handful of very old, adopted drugs from other medical specialties — mainly from oncology. I would convey the message to other nephrologists that the complication rates with this device are zero to none.

Although it may require initially some efforts by the nephrologists to get patients treated with the LIPOSORBER® device (in terms of getting access to the device), these efforts will likely be eventually rewarded.

In general, I think we should not spend much time with the other treatments if we see that they are not working or failing. Doctors should consider embarking on this treatment modality rather sooner, as sooner they expose their patients on this treatment (before more significant damage is done to the kidney), more likely the patients will have a good response.

How early do you suggest starting the treatment?

ZARITSKY: FSGS is one of these diseases that can aggressively decrease kidney function, and once that kidney function is gone, there’s no getting it back. The LIPOSORBER® is really one of these treatments that after patients have tried other treatment modalities, you want to treat them as soon as possible.

PEEV: Ideally within the first 8-12 weeks after presentation. If you see the patients not responding to first-line therapies in 8-10 weeks following the initial presentation with recurrent FSGS, I would recommend initiating this treatment as soon as possible. When left untreated this condition is frequently associated with allograft loss, despite the best efforts of the transplant team.

 

For more information about Kaneka’s LIPOSORBER® Trial, click here and here.

Levine succeeds NephCure co-founder Irving Smokler in the position

KING OF PRUSSIA, Pa. (June 15, 2021) — NephCure Kidney International (NephCure) announced today the election of longtime volunteer and board member Michael Levine as the new Board of Directors President. Levine, who joined NephCure’s Board of Directors in 2009, succeeds Irving Smokler, NephCure’s co-founder who has been with the organization since its inception in 2000. NephCure is one of the only organizations dedicated to finding better treatments and a cure for Nephrotic Syndrome and other rare, protein-spilling kidney diseases.

“I’m beyond proud of all we have accomplished over the past 21 years,” said Smokler. “We’ve gone from knowing relatively nothing about Nephrotic Syndrome and FSGS to now a much better understanding of genetic causes and pathways, and we’re likely only a couple years away from having our first approved therapies. Some of this is due to the $40 million we’ve raised for research. It’s been a pleasure to be a part of this organization’s creation and success. I am confident in our future and in Michael’s leadership and passion for NephCure’s mission.”

Levine has a special connection to NephCure — his son, Matthew, was diagnosed with focal segmental glomerulosclerosis (FSGS) in 2006, when he was only 2 years old. Shortly after Matthew’s diagnosis, Levine and his wife, Dana, joined NephCure in the pursuit of support and information.

Before long, Levine became a dedicated volunteer, later advancing to the Board of Directors’ Executive Committee, which he’s served on since 2009. Levine takes a leading role in planning and running both Countdown to a Cure New York, NephCure’s largest annual fundraising event, and the yearly All In for a Cure golf tournament and banquet. These events have helped raise millions of dollars to support NephCure’s mission of saving kidneys and saving lives.

Professionally, Levine has served as the president of L&L Painting for more than 14 years. The New York native’s deep passion for charity and helping others has also led him to join the Board of The Curetivity Foundation and actively contribute to various other charitable organizations throughout his life.

“My mission has always been to help find a cure for all the warriors battling FSGS, Nephrotic Syndrome, and other chronic kidney diseases,” Levine said. “They are waiting for us to deliver a cure. We will not fail them under any circumstances — failure is not an option.”

About NephCure Kidney International

NephCure Kidney International’s mission is to accelerate research for effective treatments for rare forms of Nephrotic Syndrome, and to provide education and support that will improve the lives of those affected by these protein-spilling kidney diseases. Founded in 2000 by a group of committed patient parents, NephCure has invested more than $40 million in kidney disease research and helped create a landscape where there are now nearly 30 interventional drug trials for primary glomerular kidney diseases. NephCure is a U.S. tax exempt 501(c)(3) public charity.

 

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We know that many of you may have questions on the recent regulatory update from Travere Therapeutics on their sparsentan program for FSGS. We’re posting this to help you understand what it means:

• Travere reported that despite the DUPLEX Study achieving its interim endpoint, the FDA indicated in recent interactions that the data from the DUPLEX Study are not yet adequate enough to support accelerated approval
• Travere noted that FDA has acknowledged the high unmet need and the limited treatment options for people living with FSGS
• For anyone participating in or following the DUPLEX Study, there are no changes to report at this time. The study will continue as planned to the final endpoint after 108 weeks of treatment
• Travere is continuing to engage with regulators about generating additional data from DUPLEX in the first half of next year with the gold of submitting for accelerated approval in 2022
• This means that sparsentan could potentially gain accelerated approval in the U.S. in 2023
• Patient retention in the study is critical to providing the FDA with most robust data package possible to support a potential approval at the appropriate time
• Travere remains confident in the potential for sparsentan to become a new treatment standard for FSGS, if approved
• Travere also recently announced that their Phase 3 PROTECT Study in IgAN has completed enrollment and interim data from the trial are expected in August of this year
• The interim data could also lead to an accelerated approval submission for IgAN

To read Travere Therapeutics’ original press release, click here.

Still want to learn more about how a drug gets approved by the FDA? Here is an FAQ list to help you find the information you’re seeking.

How does the FDA determine which study drugs are eligible for accelerated approval and which follow the normal regulatory timeline? 

The purpose of the FDA’s accelerated approval program is to get important new drugs to patients in need earlier. Generally speaking, the drug must have an impact on factors like survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more seriousone. The drug must fulfill an unmet medical need, which the FDA defines as providing a therapy where none exists or providing a therapy which may be potentially better than an available therapy.

How does this news impact my participation in the trial?

This news doesn’t change anything about your participation in this study. In fact, it’s very important that you remain in the study. Your continued participation is the only way Travere’s sparsenten will retain the potential to be granted accelerated approval. Please continue to do everything you are currently doing and comply with all study protocol/requirements. Be sure to talk to your study doctor if you have questions.

The FDA’s response to Travere’s request for accelerated approval was, ‘the available data from the interim assessment of the DUPLEX Study would not be adequate to support an accelerated approval at this time.’ Will they be able to submit for accelerated approval at a later time?

Although Travere was not granted accelerated approval at this time, they may still be able to submit for accelerated approval once additional data accrue in the DUPLEX Study. Subject to further discussions this summer, those data may become available to FDA in the first half of 2022.

What does this mean for Europe?

Travere continues to work through the conditional marketing authorization process and anticipates meeting with European regulators this summer to discuss next steps. Subject to their upcoming discussions with EMA, Travere is still planning for a submission in Europe this year. They expect to provide an update in the coming months.

 

Have you or your loved one been diagnosed with FSGS? We have resources for you.

The rates of severe kidney disease are high in individuals who are African American, Hispanic black, Afro-Caribbean, or of African ancestry. This could be due to differences in the genetic makeup in the APOL1 gene found typically in individuals with recent African, Caribbean, or Latin American descent. These differences in the genetic makeup are associated with increased rates of hypertension-associated kidney failure, FSGS, HIV-associated kidney disease, and other forms of nondiabetic kidney disease.

Fast facts about APOL1 FSGS:

• Black Americans account for 32% of all kidney failure in the US
• Black Americans are four times more likely to develop kidney failure than White Americans
• Approximately 4 in 10 Black Americans on dialysis have kidney failure caused by APOL1 gene changes
• Approximately 1 in 5 people with two copies of the APOL1 gene changes will develop kidney disease
• The high-risk APOL1 genotype is present in 75% of Black patients with FSGS

Below are resources we’ve complied that might be useful for you:

This informational flyer on APOL1 FSGS breaks down the basics and helps you better understand this disease.

To download the full informational sheet, click here.

In June 2020, we hosted a NephCure U session specifically on APOL1-Associated FSGS. Dr. Jeffrey Kopp from the NIDDK lead, “Kidney Disease in Patients of African Descent: APOL1-Associated Disease” and discussed more on the diagnosis, treatment options, and clinical trials. Listen in on the hour-long educational webinar below.

NephCure co-hosted a GlomCon Clinical Trial Conference Series session on Advances in APOL1 Therapeutics on February 14, 2021, featuring Dr. Ogo Egbuna, Dr. Opeyemi Olabisi, and Dr. David J. Friedman. Click here to watch the recording of this session.

In addition to these resources, there are also clinical trials available for APOL1-Associated FSGS patients. Clinical trials look at the safety and effectiveness of potential new treatments. The main goals of clinical trials are to find new ways to prevent, detect (find) or treat diseases or health conditions, and to make sure potential new treatments or therapies work well and are safe for people.  Check out some pre-screener questions below, provided by Vertex, to see if their clinical trial could be a fit for you or your loved one.

• Eligible participants must meet the following criteria:
• Be male or female adults between the ages of 18 and 65 (inclusive)
• Female participants must not be pregnant or breast-feeding
• Be of African, Caribbean or Latin American descent
• Have had a kidney biopsy which has found focal segmental glomerulosclerosis (FSGS)
• Have not had a diagnosis of kidney disease other than FSGS
• Be willing to complete the investigational apolipoprotein L1 (APOL1) gene test
• Be willing and able to follow the study instructions

To learn more about Vertex’s clinical trial, click here.  If you meet the preliminary criteria listed above, find the location closest to you and click the “I’m Interested” button to get in touch with an investigator for additional evaluation of eligibility.

You can find a full list of clinical trials for all protein-spilling kidney diseases on KidneyHealthGateway.com.

Need an on-the-go snack? Want to switch up the breakfast routine? Try making some of Chef Sachet’s kidney-friendly granola. As a mother and caregiver to a young boy suffering from FSGS, her recipes are tried and true for those following kidney conscious diets.

Granola Recipe

Prep Time: 5 min

Cook Time: 30 min

Yield: A LOT!

Ingredients:

• 6 cups oats
• 3 cups toasted shaved almonds
• 1 1/2 cups toasted sunflower seeds
• 1 cup unsweetened toasted coconut flakes
• 1 cup plumped raisins, dried cranberries
• 1 cup pure maple syrup
• 1 cup honey
• 1/2 cup coconut oil
• 2 tsp ground cinnamon (optional)

Instructions:

1. In a large bowl, toss oats with honey, syrup and oil.
2. Lay onto a non-stick baking sheet and toast in the over at 375 degrees for 20 min (or until oats are toasted and stiff). Be careful as to not over toast the oats as they will burn and turn bitter!
3. Let oats cool completely, then toss with other ingredients.
4. Store in a sealed cereal container or mason jar.

Important tips:

• Nuts (always use unsalted) provide a great source of protein for those trying to stay away from high phosphates in meat.
• Add some m&m’s and dried apricots and you got yourself a yummy trail mix!
• Add some yogurt, fresh fruit, and a drizzle of honey and you got yourself a delicious breakfast alternative!

Goldfinch Bio is a biotechnology company based in Cambridge, MA which focuses on advancing kidney precision medicine. Its mission is to deliver disease-modifying precision medicine that brings hope and renewed quality of life to people living with kidney diseases. We recently spoke with Goldfinch Bio’s Dr. Liron Walsh, Vice President Clinical and Translational Nephrology, who explains more about the company’s precision medicine approach, breaks down what podocytes are, and speaks more on its Phase 2 clinical research trial, TRACTION-2, which is currently enrolling patients.

What is precision medicine?

The causes of kidney disease are unique among groups of individuals. In diseases such as focal segmental glomerulosclerosis (FSGS), the causes of disease can vary from genetic to environmental. However, current treatments for FSGS are the same regardless of the cause.

With these “one-size-fits-all” approaches, some patients respond to treatment, while others do not. Many patients experience harmful side effects from these treatments with little to no benefits.

The goal of precision medicine is to develop treatments which are specifically designed to treat the underlying cause of an individual’s kidney disease. In this way, patients can receive the right medicine and avoid treatments which are not going to be helpful or may even be harmful.

Today, precision medicine is often used to treat cancer. By first understanding the genetic makeup of a patient’s tumor, a doctor can then choose the best medicine to specifically treat that patient’s cancer. This approach has greatly improved the lives of many people with cancer.

Precision medicine is now on the horizon for people with kidney diseases. Patients, nephrologists, and kidney researchers are working together to better understand the causes of kidney diseases. Through this deeper understanding, precision medicine will help develop treatments that target the specific causes of kidney diseases like FSGS and minimal change disease (MCD). Precision medicine holds promise to improve treatment outcomes and quality of life for many people living with kidney disease.

Goldfinch Bio and Precision Medicine

Goldfinch Bio is developing a novel experimental medicine, GFB-887, with the hope of preventing the progression of kidney disease in patients with FSGS, treatment-resistant MCD (TR-MCD), and diabetic nephropathy. While these kidney diseases may seem very different, they have something very important in common– very specialized cells of the kidneys called podocytes are damaged. GFB-887 is designed to specifically target these podocytes and prevent damage.

What are podocytes?

Podocytes are very specialized cells that wrap around the blood vessels of the kidneys. They form a network with other nearby podocytes to prevent the body from losing important proteins, such as albumin, while at the same time, filtering out waste. Normal functioning podocytes are very critical to our health.

When podocytes are damaged, gaps form in the barrier and important proteins are lost in the urine. This is commonly referred to as ‘spilling protein in the urine,’ and is an early sign of kidney disease. Patients with damaged podocytes experience swelling, weight gain, and fatigue. Unfortunately, damaged podocytes cannot heal, and they cannot be replaced by new, healthy podocytes. The kidney tries to repair the damage by creating a scar, much like the scar from a cut. Over time, more damage and more scarring will lead to kidney failure. By protecting the podocytes from being damaged in the first place and ensuring that the podocytes can function normally, it may be possible to prevent or delay kidney failure.

What makes the Goldfinch Bio team different than other pharmaceutical companies?

First, we are focused on advancing treatments for people with kidney diseases. Second, we are pioneering precision medicine for kidney diseases. While precision medicine is often used in cancer, and some rare genetic diseases as well, they are an entirely new area of drug research and development for kidney diseases. We are deeply committed to bringing innovative treatments to people with kidney diseases and working very closely with the patient community as partners.

Goldfinch Bio’s tagline is ‘Saving Kidneys, Ending Dialysis.’ How did you come up with this?

Our tagline– Saving Kidneys, Ending Dialysis–  is a shortened version of our vision, which is “We aspire to save kidneys and end dialysis.” We know that for many patients, kidney transplant and dialysis are the only treatment options. Unfortunately, kidney transplant may not be an option for many patients and is associated with significant long-term complications, and the experience of dialysis is very difficult. Through our precision medicine approach, we want to bring new, effective treatment solutions to patients so that we can give them hope and a renewed quality of life. We finalized our vision by hosting a focus group with people living with kidney disease to really understand what was important to them. A resounding theme emerged: these individuals expressed to us that they would give anything to avoid dialysis. And, from there, our new vision emerged.

Can you tell us more about your ongoing clinical trial?

The TRACTION-2 clinical research trial is evaluating our investigational precision medicine, GFB-887, for the potential treatment of FSGS, TR-MCD, and diabetic nephropathy. The purpose of the trial is to determine if GFB-887 is safe and may help people who have high levels of protein in their urine due to kidney diseases caused by podocyte injury. For more information on the trial, you can visit tractionclinicaltrial.com or at Kidney Health Gateway.

What are you most looking forward to at Goldfinch Bio?

We are very excited about the recent creation of our FSGS Patient Advisory Board.  We have created this board to foster a close working partnership with the patient community. For National Kidney Month, we held a virtual panel discussion with our board members. You can learn more about our Patient Advisory Board and watch the panel discussion here. We are very excited to continue to collaborate with this Board to ensure we have a patient-centric approach and mindset throughout our company.

To learn more about the TRACTION-2 clinical trial, click here. To see a full list of clinical research opportunities, and to find the trial best for you or your loved one, visit KidneyHealthGateway.com.

This article was developed in partnership with Goldfinch Bio, Inc.