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.

GLP-1 Class Update: Rybelsus Gains Cardiovascular Indication

Another GLP-1 has expanded its label. On October 17, 2025, Novo Nordisk announced FDA approval of a new indication for Rybelsus (semaglutide), the oral GLP-1 receptor agonist, to reduce the risk of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes (T2D) who are at high risk for these events.

In the pivotal trial (SOUL), Rybelsus 14 mg achieved a 14% relative reduction in MACE risk at 4 years compared with placebo. This result is consistent with the GLP-1 class, similar to dulaglutide (Trulicity) and liraglutide (Victoza), and somewhat lower than the 26% reduction seen with injectable semaglutide (Ozempic). That said, these figures should be compared with caution, as study populations and follow-up durations differ. When selecting a GLP-1 for cardiovascular risk reduction, the choice should be based on indication and comorbidities, patient preference, and formulary access.

The table below compares GLP-1 agents with cardiovascular indications:

• Some products have FDA approval only for individuals with established cardiovascular disease, while others are approved for those without established CVD but considered at high risk.
• MACE stands for major adverse cardiovascular event.
• NNT represents the number of patients that need to be treated to prevent one cardiovascular event.
• Effectiveness in A1C lowering and weight reduction is ranked from 1 (most effective) to 4 (least effective). Notably, tirzepatide (Mounjaro/Zepbound), the most potent agent for both glycemic control and weight loss, is excluded from this table, as it has not yet been approved for reducing the risk of major cardiovascular events.

Key takeaways for plan sponsors: This approval highlights the importance of staying informed about new FDA indications and how PBMs incorporate them into coverage. The Rybelsus label expansion is unlikely to create a surge in utilization since this product was already covered for T2D, but it underscores a larger concern for plan sponsors. It is essential to verify how your PBM handles label expansions for weight-loss GLP-1s, particularly, when those products are excluded from coverage.

For example, Zepbound’s approval for obstructive sleep apnea in adults with obesity introduces a potential gray area. If a plan excludes weight-loss medications, will the PBM still add Zepbound for its new indication? Understanding this in advance is critical to prevent unexpected claims and costs. Prism continues to work closely with PBMs to ensure coverage decisions accurately reflect each client’s benefit design documents, helping avoid surprises during year-end reviews and ensuring alignment between intent, policy, and execution.

IQVIA Institute: Global Drug Expenditure Remains Steady at 15% of Healthcare Costs

The IQVIA Institute for Human Data Science released its latest report, “Drug Expenditure Dynamics 2000–2022,” offering one of the most comprehensive looks at global medicine spending trends across 12 major markets. Despite growing attention on pharmaceutical costs, the data show that drug spending has remained remarkably stable, averaging 15% of total healthcare expenditure, for more than two decades. Let’s unpack the numbers…

Key Highlights

• Stability across time: Drug spending as a share of total healthcare costs has remained between 15–17% since 2000, converging around 15% across developed markets.
• Wide variation by country: The U.K. (9%), Canada (11%), and Ireland (11%) remain the lowest, largely due to strong cost controls, generic substitution, and price negotiations. Japan (20%) and South Korea (19%) rank highest, but mainly because of lower overall healthcare spending, not higher drug costs.
• United States outlier: The U.S. leads the world in absolute and per-capita healthcare spending ($13,192 per person), with drug spending of $1,337 per capita, roughly 15% of total healthcare spend, consistent with the global average.
• Healthcare costs are rising faster than drug costs: Total healthcare spending has grown much faster than drug spending since 2000, driven by hospital, physician, and administrative costs. Medicines, in contrast, have seen slower growth due to generic and biosimilar competition, loss of exclusivity, and policy interventions.
• Data gaps persist: Official data from the OECD still omit hospital drugs and post-rebate figures, underestimating true total drug expenditure. IQVIA supplemented these gaps using proprietary data, national reports, and adjusted purchasing-power methods to normalize cross-country comparisons.

Missing the GLP-1 Surge (2023–2025)

While the report provides valuable historical context, it does not capture the transformative impact of GLP-1 medications that accelerated between 2023 and 2025. This period saw unprecedented adoption of semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) across both obesity and diabetes populations.

If included, one could speculate that these years would likely shift the 15% equilibrium upward, particularly in the U.S. market, reflecting both utilization growth and limited generic/biosimilar offsets. The next IQVIA update may show this “GLP-1 era” as the first major inflection point in decades of otherwise stable drug-to-healthcare cost ratios.

HIV Prevention Landscape: Yeztugo vs Apretude

On June 18, 2025, the FDA approved Gilead’s Yeztugo (lenacapavir) for HIV pre-exposure prophylaxis (PrEP). The product offers twice-yearly dosing, intended to improve adherence by reducing the number of required injections. Its main competitor, ViiV Healthcare and GSK’s Apretude (cabotegravir), has been available since 2021 for the same indication, administered once every two months (6 doses annually).

At first glance, Yeztugo appeared to hold a competitive advantage due to its less frequent dosing schedule. However, new data indicate that Yeztugo may not be the patient-preferred option. Findings from ViiV’s CLARITY study suggest that Apretude may be better tolerated, which could have significant implications for adherence and long-term success. Although these results come from a study sponsored by ViiV, the tolerability and patient experience data are worth noting.

CLARITY Study Highlights

• The study compared a single-dose of Yeztugo (lenacapavir) with Apretude (cabotegravir) in 63 HIV-negative adults.
• 69% of participants rated Apretude injections as “totally or very acceptable,” compared with 48% for Yeztugo.
• 90% of participants and 86% of healthcare providers preferred Apretude over Yeztugo.
• The most common reasons for patient preference of Apretude included less pain during and after injection, smaller and shorter-lasting injection nodules, and overall better tolerability.
• Healthcare providers cited fewer and less severe side effects as the primary reasons for favoring Apretude.

In addition to its tolerability advantage, Apretude carries a lower annual gross cost at approximately $24,755 compared with $28,128 for Yeztugo. Cost, comfort, and adherence all play key roles in therapy selection, particularly given the Affordable Care Act’s $0 coverage requirement for USPSTF-recommended HIV PrEP medications. As the long-acting PrEP market evolves, understanding the nuances between federal guidelines, patient preference, clinical efficacy, and cost will be crucial for coverage strategy and formulary design.

FDA Rewrites the Biosimilar Playbook

After last month’s buzz on tariffs, most favored nation, and direct to consumer pricing, the FDA/Trump administration announced another focus for addressing drug prices on October 29: expediting the process of developing biosimilars. In a move aimed squarely at the high-cost biologic market, the agency announced steps it would be taking to cut the typical biosimilar development timeline nearly in half, from roughly 5–8 years down to about 3–4.

Until now, manufacturers were required to run costly human “switching” and comparative studies to prove sameness to the reference biologic, an expensive detour that often added years and millions of dollars to development. The new draft guidance flips that script: when advanced analytical testing can prove similarity, those studies may no longer be necessary. The FDA is also backing away from requiring switching studies for interchangeability, opening the door for faster pharmacy-level substitution.

Shortening biosimilar timelines by dropping switching studies raises fair questions. These studies were originally designed to confirm that patients could move between a brand and its biosimilar without added risk or loss of efficacy. The FDA now believes modern analytical and pharmacokinetic/pharmacodynamic testing can reliably demonstrate similarity without those large human trials. Europe has already gone this route. In 2023, the European Medicines Agency (EMA) and Heads of Medicines Agencies (HMA) stated that EU-approved biosimilars are considered interchangeable and that additional switch studies aren’t required.

For plan sponsors, this means the biosimilar pipeline could be rolled out faster than anticipated, especially in high-spend categories like oncology and autoimmune disease. Provided this new process takes hold, expect competition (and savings) to show up earlier, especially as we learn from recent biosimilar launches like Humira and Stelara. Formulary and contracting teams should be ready to pivot quickly as launch timelines compress and rebate dynamics shift. So where does that leave us? Let’s take a quick look at the current landscape and what’s on the horizon as the next round of high-impact biosimilar launches takes shape.

For patients, faster approvals could translate to earlier access to lower-cost biologics and fewer administrative hurdles at the pharmacy counter. The next hurdle won’t be regulatory (nor is it necessarily a new hurdle). Rather, it will be education and confidence in switching. The Prism clinical team continues to closely monitor the biosimilar pipeline as well as safety and efficacy studies that support their use. Don’t hesitate to reach out if you’re looking for more info on how to responsibly and effectively approach biosimilar transitions.