Understanding the Complexities Associated with IgA Nephropathy

Nefecon

Barrett and other researchers ran a trial on Nefecon, a steroid targeting the gut, for treating IgA nephropathy.

“Strangely, nephrologists are concentrating on the gut because we believe that the IgA that deposits within the filters of the kidneys originate from the parts of the immune system that lines the gut,” shared Barrett. “Therefore, developing a medication that specifically targets the immune system of the gut is a way of potentially turning off the production of this pathogenic IgA that then, in turn, stops this IgA depositing in the kidneys.”

The Nefecon trial tested a new medication called Tarpeyo (budesonide), also known as Nefecon, to prevent kidney damage for IgA nephropathy patients. Budesonide is a corticosteroid that prevents inflammation.

“The rationale behind Nefecon is that it is a steroid medication, specifically packaged in a way that delivers this steroid to the terminal ileum — the last part of the small intestines because that part of the small intestines is very enriched with immune cells,” noted Barrett.

Study Design

PharmaNewsIntelligence asked Barrett to describe how the study was designed and its outcomes. To begin, he explained the phase II study. “That was conducted in Europe and was a three-arm study looking at a placebo, 8 mg, and 16 mg of Nefecon for nine months,” revealed Barratt.

To determine the drug’s efficacy, researchers, including Barratt, looked at the interventional impacts on proteinuria at the nine-month mark. Barrett said that Nefecon proved to be effective in reducing proteinuria in patients with IgA nephropathy. Proteinuria was also used as an indicator of kidney failure.

Additionally, Barratt noted, “the phase II study showed us that we can target the gut, which can protect the kidneys in patients with IgA nephropathy.”

In addition, a global phase III study is being conducted with a similar procedure. Rather than looking at three arms, the international study compares 16 mg of Tarpeyo with a placebo. In addition to looking at proteinuria, the longitudinal, global study will look at the change in kidney function, referred to as eGFR, at the end of the two-year study.

Patient Recruitment

PharmaNewsIntelligence asked Barratt to explain the patient recruitment process. “This study was designed to look at patients with a high risk of progressive kidney function loss as defined by international criteria,” he responded.

“Patients who have more than 1 g of proteinuria despite optimized supportive care are at high risk of progression, and those were the patients included in this study,” continued Barratt. “Clinicians know there is a massive unmet need for these patients to have safe and effective treatments, and we don't have anything for them now.”

Side Effects of the Medication

Considering the strength of steroids and the commonly associated side effects, PharmaNewsIntelligence was curious about the side effects associated with the drug. Barret explained, “patients noticed some side effects, and because Nefecon is a steroid, there is a small amount of systemic absorption into the bloodstream.”

He shared that the side effects that patients in the study observed were similar but not as severe as those experienced with other steroids. 

“There were very few patients who decided to stop the treatment because of these side effects, and any of the side effects that did develop reversed when the treatment was stopped,” he noted. “The drug was very well tolerated. The effects were commonly associated with a drug like prednisolone.” Barratt continued to emphasize that the side effects were not common among the patients in the study.

Kidney Disease Support

Kidney disease is an incredibly challenging disorder that affects millions of people worldwide. According to the CDC, chronic kidney disease impacts 37 million adults in the United States alone.

Even though kidney damage is irreversible, very few people understand kidney disease well. Most people diagnosed with kidney disease are diagnosed at later stages of the disorder when the condition is already a burden. The CDC also states that nearly 40% of people who have chronic kidney disease and are not on dialysis do not know they have it.

Barret discussed the issues surrounding kidney disease education and the best ways to address them.

Cost Concerns

A primary concern associated with chronic kidney disease is its financial burden. “One thing healthcare professionals need to accept is that this is a disease of young people who have a significant lifetime risk of developing kidney failure requiring dialysis,” began Barratt. “Dialysis and all the complications of progressive kidney failure are incredibly costly. A phenomenal amount of money in the US alone is spent on providing dialysis. It is far more cost effective to prevent a young person from developing kidney failure than it is to treat kidney failure once it's developed.”

According to the American Society of Nephrology, the annual economic burden of end-stage renal disease is $32 billion in the US. Furthermore, each month, the average patient with end-stage renal disease accrues $14,399 in healthcare costs each month. Treating the disease early and preventing additional damage alleviates the financial burden on the payer, providers, and patients.

Awareness

Unfortunately, there is a lack of awareness surrounding kidney disease. Many patients do not understand their risk factors, and few providers have a well-rounded understanding of the disease.

“It's a real challenge because often kidney failure is the silent killer,” emphasized Barratt. “Unless providers or patients look for it, they’re not going to find it. Healthcare professionals need to raise general awareness. In the broader common causes of kidney failure, diabetes is the number one cause, so we need to spread awareness.”

While kidney disease is associated with diabetes and other comorbidities, it can be challenging for providers to recognize rare kidney diseases such as IgA nephropathy.

“The challenge for these rare kidney diseases, like IgA nephropathy, is that it's not something that often comes to mind for primary care physicians, patients, and general physicians, because it's rare. Most primary care physicians may only ever have one or two patients with IgA nephropathy in their career, so they can't be experts, and it's not something they think of,” said Barratt.

Barratt told PharmaNewsIntelligence that increased awareness of kidney disease amongst members of the healthcare industry and the general public is necessary. Providers are encouraged to act on the slightest indications of kidney disease by pursuing additional testing or referring a patient to a specialist.

Looking Ahead

Despite the challenges associated with kidney disease, specifically rare kidney disease, Barrett notes, “this is a very exciting time for rare kidney diseases. There's been a lot of support from the regulators to look at attainable endpoints. We have many companies who've been energized by the changing regulatory framework and are investing time, money, and effort in rare kidney diseases.”

As research progresses and additional therapies and treatments are made available, providers are encouraged to monitor kidney disease and seek further education on preventing, detecting, and treating the disorder.