November 2025 Clinical Update
The Rapidly Evolving Economics of GLP-1s and Biosimilars
In a marketplace where brand drug pricing tends to follow a predictable trajectory, directional shifts are rare enough to make everyone pause. November delivered several such moments. Prices on specific products moved downward, but with an important qualifier. Many of these reductions appeared in the direct to patient channel, which operates entirely outside the traditional pharmacy benefit and requires cash payments. Still, direct to patient activity was only part of the story, with Mark Cuban also introducing a new biosimilar. Taken together, November’s announcements underscore a broader theme. Plan sponsors must actively monitor emerging price signals and be prepared to adapt strategy in real time, while staying grounded in operational reality and clinical responsibility.
Let’s start with GLP-1’s. On November 6th, President Trump introduced the next step in his most favored nation pricing effort by announcing agreements with Eli Lilly and Novo Nordisk to reduce payments for their weight loss products. These lower prices will apply to cash-paying patients through the TrumpRx platform beginning in 2026. Novo Nordisk added a follow-on update on November 17th, announcing immediate price reductions for existing self-pay patients on Wegovy and Ozempic. At this point, keeping track of which doses are discounted through which channel on which date has become its own full-time job. Prices are changing quickly enough that the accompanying table reflects what we know today, with no guarantee it will still be current by the time you’re reading this sentence. Net costs are based off current average rebate estimates.
Moving to our second favorite topic after GLP-1 products, the biosimilar market continued its rapid evolution. The Stelara biosimilar category, in particular, has moved at a pace that stands in contrast to the slower rollout of Humira biosimilars in 2023. Interest among plan sponsors is high, and the pricing pressure has intensified quickly. CivicaScript’s $985 per 90mg syringe option seemed difficult to beat, yet Mark Cuban’s Cost-Plus Pharmacy introduced Starjemza at $415 per 90mg syringe, including shipping. Starjemza is interchangeable with Stelara, which allows for simple one-to-one switching and positions it as the top contender for lowest net cost in the category.
So, what should plan sponsors take away from this? Direct to patient pricing offers real savings, but access is complicated. Pre-funded card or stipend models exist to help members purchase these products outside the pharmacy benefit. However, these options still lack key infrastructure such as utilization management controls, accumulator integration, and claims connectivity. That combination creates operational friction and potential clinical blind spots if pharmacists and providers cannot see the full scope of a member’s therapy.
Biosimilar savings, by comparison, are far more accessible. Every plan sponsor should be asking how to ensure access to the lowest net cost product available in the category and how quickly member transitions can be operationalized.
Stepping back, the message is straightforward. These price changes should prompt plan sponsors to engage their PBMs and ask how they plan to compete with the lowest net cost options now emerging across multiple channels. The market is shifting quickly, and strategy must shift with it.
Caplyta’s New Indication and Its Market Implications
Caplyta, or lumateperone, is a second-generation antipsychotic originally approved in 2019 for schizophrenia and bipolar depression. It carries one of the highest price tags in the category at roughly $21,000 per year, compared to under $100 annually for generic alternatives like aripiprazole or quetiapine. Branded competitors Vraylar and Rexulti offer only slightly lower prices. What sets Caplyta apart is its remaining window of exclusivity. Rexulti is expected to face generic competition around 2029 and Vraylar around 2030. Caplyta is protected until 2039, giving it a long period of uninterrupted brand pricing.
On November 6th, the FDA expanded Caplyta’s labeling to include adjunctive use with antidepressants for major depressive disorder (MDD), increasing its potential reach. The following snapshot helps illustrate the size of that market.
Caplyta’s Expanded Market: Population Snapshot
Bipolar Disorder and Schizophrenia
- 2.8% of the U.S. population is estimated to have bipolar disorder, approximately 9.5 million individuals
- 0.25 to 0.64% is estimated to have schizophrenia, approximately 1.5 million individuals
- 10 to 20% of patients diagnosed with depression may actually have bipolar disorder
- Combined potential pool for bipolar disorder and Schizophrenia (current market): ~11 million individuals
Major Depressive Disorder (MDD)
- 21 million adults experienced at least 1 major depressive episode in 2021
- 8.9 million received medication treatment
- 2.8 million meet criteria for treatment-resistant depression, the group aligned with Caplyta’s new indication
Plans can still apply reasonable utilization management for this new MDD use, such as requiring 2 antidepressant trials to confirm treatment resistance, confirming adjunctive rather than monotherapy use, and using annual reauthorization cycles. These are permissible under Mental Health Parity as long as they are no more restrictive than comparable medical and surgical criteria.
Across phase 3 adjunctive MDD studies, Caplyta produced symptom improvements consistent with other atypical antipsychotic augmenters. Its key advantage is tolerability. Unlike aripiprazole, Rexulti, or Vraylar, which carry notable rates of akathisia (movement disorder characterized by restlessness), Caplyta demonstrated placebo-like extrapyramidal symptoms and minimal restlessness. It also maintained a neutral metabolic profile with little to no weight gain or laboratory abnormalities. Quetiapine XR remains a more sedating option with a higher metabolic burden.
Overall, Caplyta’s efficacy is class-consistent, but its tolerability profile may offer an advantage for certain patients. For plan sponsors, appropriate utilization management and patient-specific therapy selection will be essential as its use expands into the MDD space.
When a $595,000 Drug Meets a $60,000 Alternative
Familial chylomicronemia syndrome, or FCS, is a rare genetic form of severe hypertriglyceridemia (high triglycerides) that places patients at high risk for acute, life-threatening pancreatitis. Tryngolza, approved in December 2024, became the first medication to be commercially available for this condition. Although FCS is extremely rare, the financial impact is significant. Tryngolza, manufactured by Ionis Pharmaceuticals, carries an annual price of $595,000, creating substantial exposure for any plan that encounters even a single claim.
Redemplo entered the spotlight on November 18th when the FDA approved it for the same indication. The manufacturer, Arrowhead, positioned Redemplo at a markedly lower annual price of $60,000. Arrowhead has been transparent about its pricing strategy, noting that Redemplo has potential applicability in a far more common condition currently in clinical trials: severe hypertriglyceridemia, or SHTG. SHTG affects an estimated 3 million individuals in the U.S., compared to the very small FCS population. Ionis is also studying Tryngolza for SHTG, signaling a competitive future market. Arrowhead additionally highlighted that 93% of FCS patients who experience acute pancreatitis require hospitalization, with an average 10-day inpatient stay costing approximately $60,000 per episode.
The comparison table below outlines key differences between the two agents. While cross-trial data must always be interpreted cautiously, preliminary review suggests that Redemplo may offer a clinical advantage and clearly delivers benefits in cost, administration, and safety considerations.
GLP-1 Falls Short in Alzheimer’s: EVOKE Trials Miss Primary Endpoint
After a whirlwind of GLP-1 label expansions, it appears one indication on the ever-growing list will not be added as a new FDA approval, for now. Novo Nordisk announced that the EVOKE and EVOKE+ Phase 3 trials evaluating oral semaglutide (Rybelsus) in early Alzheimer’s disease did not meet the primary endpoint of slowing clinical decline.
Although FCS is rare, the pharmacy benefit world is no stranger to ultra-high-cost claimants emerging only after a claim has already been processed. Redemplo presents a meaningful opportunity for PBMs and plan sponsors to get ahead of this risk. Preferring Redemplo as a clinically appropriate lowest-net-cost option may help plans avoid the financial shock associated with a future Tryngolza claim.
Summary of the Trials
- EVOKE and EVOKE+ enrolled approximately 3,800 adults aged 55–85 with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
- Participants received daily oral semaglutide titrated to 14 mg and were followed for 104 weeks.
- The primary endpoint was change in CDR-SB, a standard measure of disease progression.
- The outcome showed no statistically significant difference versus placebo, despite modest biomarker signals that suggested the drug was engaging relevant pathways. This disconnect between biomarker activity and clinical outcomes indicates that any biological effect was not strong enough to slow meaningful cognitive decline over the 2-year study period.
The trials were closely watched amid growing interest in GLP-1s as potential neuroprotective agents. While semaglutide did not demonstrate disease modifying effects, the Alzheimer’s treatment landscape has advanced over the past 3 years. The FDA approved the first two disease modifying therapies, Kisunla and Leqembi. Earlier this year, Biogen and Eisai also introduced Leqembi Iqlik, a once weekly subcutaneous formulation that allows at home administration and avoids the infusion burden associated with the original IV product.
Plan sponsors may no longer expect a new wave of Alzheimer’s related GLP-1 utilization, though the results are disappointing for individuals affected by the disease and their families. The absence of a new indication avoids additional cost pressure in an already high spend category. Continued monitoring of the Alzheimer’s pipeline remains important, particularly as real world data emerge for Kisunla, Leqembi, and the subcutaneous Leqembi Iqlik.
