August 2025 Clinical Recap
Jake Goll, PharmD (jake.goll@theprismhealthgroup.com) serves as the clinical consultant at Prism Health Group, where he provides end-to-end oversight of clinical strategy through in-depth data analysis, proactive consultation, and subject matter expertise.
Repatha’s Expanding Role: Managing Cost and Access
Last month, the FDA expanded Repatha’s label to include reducing the risk of major adverse cardiovascular events (MACE) in adults at increased risk, even without established cardiovascular disease (CVD). Until now, this benefit was reserved only for patients with documented CVD. Repatha also carries approvals for hyperlipidemia and multiple forms of familial hypercholesterolemia. While high LDL, hypertension, diabetes, and smoking remain the classic risk factors, this new indication broadens eligibility and could drive utilization upward. At a net cost of about $310 per month, plan sponsors should closely monitor trends, since even modest uptake could translate into meaningful spend.
That said, it’s important to remember that generic statins, which typically cost just a few cents per tablet, remain a cost-effective foundation of cardiovascular risk reduction. For patients who tolerate them, statins should stay the frontline therapy. Requiring a statin trial and failure before moving to Repatha is a practical step therapy approach that protects both clinical outcomes and plan budgets.
This label expansion is good news for patients who need more options, but it also means plan sponsors must prepare for the ripple effects: higher utilization, higher costs, and potential pressure on formularies. Now is the time to review utilization management strategies, reinforce statins as the first-line therapy, and ensure monitoring systems are in place to catch shifts in spend before they become trends. Aligning patient access with responsible plan design will help balance clinical value with financial sustainability. Some action items to consider moving forward:
- Monitor Repatha claims for new utilization patterns and cost trends
- Reinforce statins as the preferred first-line therapy
- Ensure step therapy and prior authorization edits are in place
- Reassess formulary positioning and member communications as needed
MASH Market Shakeup: Wegovy Steps In
On August 15th, Wegovy picked up yet another notch on its label with FDA approval for metabolic-associated steatohepatitis (MASH), better known to most as non-alcoholic fatty liver disease. That makes Wegovy only the second drug cleared for this indication, following Madrigal’s Rezdiffra in March 2024. The addressable market is hardly niche: roughly 6% of U.S. adults, or about 15 million people, live with MASH, and prevalence is rising.
Wegovy usually makes headlines for its hefty price tag. But for MASH, it looks like the “discount” option. A year of Wegovy carries a wholesale acquisition cost of $17,537 versus $50,077 for Rezdiffra.
From a clinical perspective, we’re still stuck with indirect comparisons. No head-to-head trials exist, so we have to look at each study in isolation. As always, these cross-trial reads should come with a large asterisk. That said, on placebo-adjusted endpoints, Wegovy appears to outperform Rezdiffra, at a fraction of the cost. It’s also worth noting that Wegovy lowers A1C, reduces cardiovascular risk, and drives weight loss, which are added benefits that Rezdiffra does not offer.
For payers and PBMs, the math seems obvious: Wegovy should be prioritized, at least as a step therapy option for MASH. But as usual, things get tricky when we consider rebate mechanics. Many plan sponsors exclude Wegovy for weight loss today. Will pharma contracting allow payers to capture manufacturer rebates if coverage is restricted to MASH only? Even without rebates, and current estimates suggest Wegovy rebates run at 45–50%, the economics still tilt in Wegovy’s favor unless Rezdiffra’s price drops substantially. All of that said, the table below summarizes some of the high-level advantages and disadvantages of each product.
The other open question is durability. Both products received accelerated approval because the FDA is still waiting to see if improvements in liver histology actually translate into better survival, fewer transplants, or reduced liver events. Until then, this is a high stakes bet on early surrogate outcomes.
Crohn’s Disease Therapy Meta-Analysis Highlights Value of Lower-Cost Options
A meta-analysis published last month in the American Gastroenterology Association’s Gastro Hep Advances sought to compare the efficacy of all available drug therapies for moderate-to-severe Crohn’s disease. With GI agents representing a steadily growing drug class, driven by high-cost biologic therapies and the rising prevalence of inflammatory bowel disease, it is important to understand which treatments provide the most value. This study synthesized results from 77 randomized controlled trials to inform utilization management strategies and guide patients toward cost-effective, clinically appropriate options.
In biologic-naive patients, adalimumab (Humira) in a high induction regimen ranked highest for inducing remission, while the combination of infliximab and azathioprine was most effective for maintaining remission. Among patients naive to immunomodulators, infliximab (Remicade) plus azathioprine and methotrexate were among the most effective induction strategies. In biologic-exposed patients, upadacitinib (Rinvoq) ranked highest for both induction and maintenance of remission, with ustekinumab (Stelara), risankizumab (Skyrizi), and vedolizumab (Entyvio) also demonstrating meaningful benefit. Notably, conventional agents such as azathioprine and methotrexate continued to show efficacy, reinforcing their role as lower-cost alternatives when appropriate based on individual patient characteristics; these drugs tend to have more side effects and require closer monitoring.
To compare therapies, the authors used a metric called SUCRA (Surface Under the Cumulative Ranking curve). In plain terms, SUCRA provides a ranking score from 0 to 100 that estimates the probability a treatment is the best among those studied. A higher SUCRA value means a therapy is more likely to be among the most effective options, while lower scores suggest less effectiveness. This method allows for easier side-by-side comparison across multiple drugs, even when head-to-head trials are lacking.
Ultimately, the results highlight that biologics frequently demonstrate similar efficacy; differences are modest and confidence intervals in the 77 studies that were analyzed often overlap. For pharmacy benefit managers and plan sponsors, this underscores the opportunity to emphasize cost-effective, clinically responsible choices. Biosimilars of adalimumab (Humira) and infliximab (Remicade) in particular remain highly effective therapies, meaning clinical outcomes can often be achieved at a fraction of the cost compared to newer agents, particularly in biologic naïve patients.
Not every Crohn’s patient requires the newest or most expensive drug. By strategically leveraging lower-cost therapies and biosimilars when appropriate, plans can ensure strong clinical outcomes while maintaining sustainable benefit design.
Semaglutide for Cardiovascular Risk: Clinical Gains vs. Cost Pressures
A recent real-world study published in JAMA Open Network evaluating 23,522 adults (mean age 56, nearly 70% with diabetes) found that semaglutide initiation led to meaningful improvements in cardiovascular risk factors. Patients experienced weight reductions of 3.8% overall (greater in those without diabetes at 5.1%), modest blood pressure improvements, lower cholesterol, and reductions in A1C for those with diabetes. All results were assessed at 13 to 24 months. Clinically, the results are encouraging, though the magnitude of benefit, particularly in weight loss, is less pronounced than what was reported in clinical trials. The study notes that adherence likely plays a role in these differences.
The financial story tells a different side. Despite these health improvements, monthly healthcare expenditures rose by an average of $80 in the 13–24 months following semaglutide initiation, excluding the cost of the drug itself, largely due to inpatient costs. Increases were seen across both diabetic and non-diabetic patients, particularly in circulatory and metabolic disease categories. The study underscores a disconnect between short-term clinical outcomes and financial impact, raising questions about cost-effectiveness in the real-world setting.
Semaglutide is demonstrating real-world improvements in cardiovascular risk factors, but it comes with higher short-term costs that continue to strain budgets as utilization grows. The long-term value story is still unfolding, and one of the biggest challenges for plan sponsors is that those savings may only be realized if employees remain with the plan long enough to benefit. Improved outcomes years down the line don’t necessarily translate into savings if these employees leave for another job. In this sense, the return on investment for therapies like semaglutide is tied not only to adherence, but also to employee retention. Adherence itself is a double-edged sword: it is essential for driving clinical benefit, but it also drives higher pharmacy spend in the short term. As with many high-cost therapies, the reality is that not all patients will achieve the same outcomes seen in clinical trials, and the timing of when those outcomes appear adds another layer of complexity for plan sponsors managing both budgets and benefits.
