What’s Next for Chronic Kidney Disease Treatment and Access

Key Takeaways

• The chronic kidney disease (CKD) treatment pipeline includes emerging endothelin A receptor antagonists (ETAs), aldosterone synthase inhibitors (ASIs), and cell-based therapies that may help slow disease progression and delay kidney failure.
• Generic SGLT2 inhibitors could reduce treatment costs while increasing pressure on manufacturers to demonstrate the added clinical value of newer therapies.
• Payers will prioritize evidence of reduced albuminuria, slower kidney function decline, improved cardiovascular outcomes, and lower total costs of care when evaluating emerging treatments.

As the CKD treatment landscape continues to expand, new therapeutic classes and emerging treatment options are creating opportunities to improve patient outcomes while introducing new considerations for payers. In this interview, Roy Moore of Clarivate’s market access team discusses the current CKD treatment pipeline, potential US Food and Drug Administration (FDA) approvals, and the growing competitive landscape. He also examines how generic competition, clinical evidence, and evolving treatment guidelines may influence formulary decisions, reimbursement strategies, and patient access to emerging therapies.

Roy Moore: My name is Roy Moore. I'm on the therapy team here at Clarivate. I've got 20 years of experience in US and global market access, working in both syndicated and consulting businesses. As it relates to the topic today, I have experience in this therapeutic area. In fact, last year I worked on a project for IgA nephropathy, which includes a lot of the same drugs and similar dynamics at play.

What does the current CKD treatment and pipeline landscape look like, and which therapeutic classes or mechanisms are generating the most interest?

Moore: There's been a lot of activity when it comes to CKD and the available therapeutics, and that will evolve over the next several years. Historically, this disease was traditionally treated with angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors. Then came mineralocorticoid receptor antagonists (MRAs), including Kerendia, which was approved in 2021. We've seen a lot of activity with the SGLT2 inhibitors, which are also used to treat diabetes. They obtained CKD indications as part of their labels. And then, we've also seen the entry of semaglutide with CKD as part of its label.

It's going to be incumbent upon the payers to be monitoring this because it's a very large population of 35 to 40 million Americans that have CKD. It is commonly comorbid with type 2 diabetes, and it’s very costly. Patients who progress may progress toward renal failure, dialysis, transplantation, things of that nature. So, there's also going to be continued unmet need for this disease. There are new drug classes coming in. Some that particularly stand out are the ETAs and ASIs. They'll be combined with the SGLT2 inhibitors to get multiple mechanisms of action to attack parts of this disease. So, we'll see a lot of activity in those areas over the next couple of years.

Looking ahead, which emerging therapies, potential FDA approvals, or label expansions could have the greatest impact on CKD treatment over the next 12 to 24 months?

Moore: The CKD landscape is expected to undergo significant changes over the next several years. As I mentioned before, SGLT2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have already entered the market, and additional therapeutic classes are in development, similar to what has occurred with IgA nephropathy. One that stands out to me is zibotentan from AstraZeneca. It's an endothelin A antagonist that would be combined with dapagliflozin to offer a dual mechanism of action to treat this disease. The combination would focus on proteinuria, which is the presence of excess protein in the urine and a key indicator of kidney disease progression. This could be an important development over the next 12 to 24 months. Another potential treatment is a cell-based therapy called rilparencel, which could help preserve kidney function and delay dialysis or kidney failure if approved by the FDA.

The pipeline extends beyond these therapies. Over the next 3 to 4 years, another class, ASIs, could enter the market. These therapies would directly block the production of aldosterone and could be combined with SGLT2 inhibitors to provide a dual mechanism of action. These drugs would likely compete with MRAs, particularly Kerendia. Lastly, GLP-1 receptor agonists have already entered the CKD treatment landscape with semaglutide. Eli Lilly has a triple agonist in development called retatrutide, which targets GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors and could compete with semaglutide. Overall, the introduction of these different therapeutic classes will make the CKD treatment landscape more dynamic, with a lot to monitor over the next several years.

As the CKD landscape becomes more crowded, how do you expect competition to evolve among SGLT2 inhibitors and newer add-on therapies? Could generics or biosimilars affect pricing or formulary decisions?

Moore: As I mentioned before, a number of additional therapeutic classes are expected to enter the CKD market. But one thing I haven't talked about is genericization. For instance, SGLT2 inhibitors are becoming the standard of care for this population, and some have already gone generic. Dapagliflozin, for example, is now available as a generic version of Farxiga, with list prices as low as $10 per month. That's going to create a benchmark for how payers assess the relative value of new therapies.

Many of the new drugs in development will be used in combination with dapagliflozin, which means additional costs. Generic availability will provide some economic relief for payers. Historically, these patients were treated with ARBs and ACE inhibitors, which are low-cost generics. The introduction of SGLT2 inhibitors added costs, but generic versions can help offset some of that burden. However, newer therapies entering the market will introduce additional costs.

As a result, payers will likely prioritize SGLT2 inhibitors as early-line treatment, reserving newer add-on therapies for patients who do not respond adequately. That means manufacturers will need to demonstrate the additional value their products provide over SGLT2 inhibitors alone. In many instances, clinical trials are designed to compare dapagliflozin monotherapy with combination therapy, allowing payers to evaluate the marginal benefit of adding a new treatment. This will likely lead payers to position some newer therapies later in the treatment sequence, particularly for patients who have not responded adequately to existing options.

This competitive landscape will also open the door to more widespread contracting. As I mentioned earlier, SGLT2 inhibitors originally entered the market for diabetes, which is a heavily contracted therapeutic area. Payers will likely expect substantial rebates, particularly in classes where multiple agents compete for formulary placement.

What evidence will payers need to differentiate emerging CKD therapies, particularly around disease progression, cardiovascular outcomes, hospitalizations, and total cost of care?

Moore: Payers are going to pay very close attention to this disease because it's extremely expensive. Estimates put the annual cost to Medicare at more than $100 billion, driven by expenses associated with dialysis, transplantation, and disease progression. New therapies in development will be welcomed by payers, but they will need to demonstrate efficacy.

Clinical trials are being designed similarly to those for IgA nephropathy, with a focus on the incremental benefits of treatment. Key efficacy measures include reductions in albuminuria, slowing the decline in estimated glomerular filtration rate (eGFR), delaying the onset of end-stage renal disease, and reducing the need for dialysis or transplantation. Payers will focus on these measures of disease progression because they can help determine whether patients will require additional treatment, which increases costs. Therapies that can delay or prevent dialysis and transplantation will be particularly valuable to payers because of their potential to reduce the total cost of care.

Cardiovascular outcomes will also be important, particularly given the overlap between CKD and type 2 diabetes. I believe therapies that demonstrate a reduced risk of heart failure, hospitalization, or mortality, along with improvements in overall cardiovascular outcomes, will be especially attractive to payers. This will be particularly true if those benefits can be demonstrated against the current standard of care or as an improvement over existing monotherapy.

What are the key access and reimbursement considerations for payers as new CKD therapies enter the market, particularly around formulary placement, treatment sequencing, and patient selection?

Moore: For payers, this is a multifaceted issue. Interestingly, when I interviewed payers last year for a project on IgA nephropathy, one explained that the disease had historically required little active management because the available drugs were all generic. However, with the introduction of newer therapies, particularly SGLT2 inhibitors, payers had to take a more active approach to managing the disease. Something similar is happening with CKD. It's a very large population, with close to 40 million Americans affected. There are different stages of the disease, and as it progresses, both the clinical and financial burdens increase. The consequences of disease progression are significant, not only for patients who may experience kidney failure but also for payers facing the high costs of hospitalization, dialysis, and transplantation.

Generic availability will also play an important role in shaping payer decisions. As SGLT2 inhibitors become available as generics, payers will benefit from lower costs. Farxiga, for example, now has generic alternatives, with some list prices as low as $10 per month. That creates a benchmark for how payers assess the value of new therapies, particularly when existing branded treatments, such as Kerendia, cost approximately $600 per month. That represents the upper end of what payers may consider acceptable unless a new therapy demonstrates significant additional benefits. Generic competition will influence those expectations, but therapies that can demonstrate downstream benefits, such as reduced hospitalizations and improved clinical outcomes, will resonate with payers because of their potential to reduce overall costs.

Clinical guidelines will also play an important role in access and reimbursement decisions. Based on my conversations with payers, I expect prior authorization (PA) requirements and treatment criteria to closely align with established guidelines, particularly when head-to-head data are available to differentiate individual therapies. This could leave treatment decisions largely in the hands of physicians, provided patients meet the necessary criteria and have progressed beyond SGLT2 inhibitors as an early-line treatment.

Manufacturers will also need to consider the impact of competition and contracting. When a lower-cost alternative offers meaningful clinical benefits, manufacturers of newer therapies will likely need to offer rebates to secure formulary access. Higher rebates may be necessary to achieve preferred formulary placement. I expect contracting and rebate negotiations to become increasingly important over the next several years as the CKD treatment landscape continues to expand.