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. He supports client and broker engagements, develops tailored insights using pharmacy claims data, and delivers clinical guidance that informs benefit design and strategic decision-making. Jake also plays a central role in educating both internal teams and external partners on emerging clinical trends, from biosimilars to gene therapies, and champions independent thought leadership across the healthcare ecosystem.

Prism is committed to delivering actionable insights that resonate with our business partners and broader audience. If you’re interested in working with us or have a clinical topic you’d like to see explored in a future edition, please reach out to us directly. We welcome the conversation.

Every year, I head into December with the same goal: slow down a bit. More time with family and friends, admiring increasingly elaborate Christmas light displays, and inevitably waiting until December 21 to order gifts. I also like to convince myself that this festive and relaxed mindset will somehow translate into a quieter month at work. As usual, the pharmaceutical market had other plans. So, without lingering too long on personal grievances (as I put the final touches on this newsletter over Festivus), let’s recap a December that delivered no shortage of market-moving developments.

-Jake

Direct-to-Patient Pricing: Big Headlines, Narrow Impact (for Now)

We’ll start with the latest updates on Most Favored Nation (MFN) pricing and Direct-to-Patient (DTP) models. On December 19, President Trump announced 9 new pricing agreements with major pharmaceutical manufacturers. The announcement had 2 distinct components:

• MFN: Manufacturers agreed to provide all State Medicaid programs with access to MFN pricing on select products.
• DTP: Several manufacturers committed to offering reduced prices directly to patients through the TrumpRx platform beginning in early 2026.

The headlines were loud. The substance is more nuanced. Any responsible benefit decision-maker should evaluate these announcements drug by drug. In many cases, the economics are far less disruptive than the press coverage suggests. Below is a practical breakdown, all costs based on typical 30-day supplies.

• Amgen – Repatha DTP price drops list price from $573 to $239. This undercuts the estimated PBM net cost of ~$279. A case where DTP is competitive today.
• Bristol Myers Squibb – Reyataz DTP price drops list price from $1,449 to $217. While this beats PBM net cost, Reyataz is less commonly used in modern HIV regimens, and the generic is available for ~$26. Headline-friendly, clinically unremarkable.
• Boehringer Ingelheim – Jentadueto DTP price drops list price from $525 to $55 versus an estimated PBM net cost of ~$293. Generic availability is expected in 2026, and broader DPP-4 class erosion is coming as Januvia and Janumet generics enter the market.
• Genentech – Xofluza DTP price drops list price from $168 to $50. Beats PBM net cost, but routing an acute flu treatment through a DTP channel raises access concerns. Speed matters here, and community pharmacy access remains critical.
• Gilead Sciences – Epclusa DTP price drops list price from $24,920 to $2,425 per fill. Total treatment cost would be ~$7,275 for a full course. Net PBM cost is unclear due to lack of rebate data, but this DTP pricing materially undercuts the authorized generic (sofosbuvir/velpatasvir), which runs ~$23,378 per course. One of the most compelling opportunities in the announcement.
• GlaxoSmithKline – Advair Diskus DTP price drops list price from $265 to $89. Typically see near-complete utilization shift to generic fluticasone/salmeterol through PBM channel. Mark Cuban Cost Plus lists the generic at ~$44, further limiting the relevance of the DTP price.
• Merck – Januvia DTP price drops list price from $330 to $100 versus an estimated PBM net cost of ~$184. Generic entry is expected in May 2026, so additional price compression is imminent regardless of DTP.
• Novartis – Mayzent DTP price drops list price from $9,987 to $1,137 versus an estimated PBM net cost of ~$7,594. This is another case where DTP pricing could represent real savings, assuming operational barriers can be addressed.
• Sanofi – Plavix and Insulin Portfolio Plavix drops list price from $756 to $16, and insulin products would be listed at $35 per month. Plavix has been non-formulary across PBMs for years due to generic clopidogrel availability at <$10 per month. Insulin pricing aligns with existing market dynamics rather than redefining them.

Bottom Line: a handful of these examples present legitimate savings opportunities. Many do not.

When evaluated individually and adjusted for net cost, generic availability, and low-cost alternatives, the overall impact of these announcements is likely far more limited than the headlines suggest.

Where these prices do matter most is for:

• Uninsured individuals
• Members in HDHPs who may be exposed to full or partial unrebated list price at the point of sale

For plan sponsors, pursuing access to DTP pricing via a pharmacy benefit carve-out should be approached cautiously. While not impossible, carve-outs require independent management of utilization controls, prior authorization, accumulators, and clinical DUR functions that PBMs typically handle (as mentioned in previous installments of Jake’s Takes). Several PBMs have indicated they are actively working to compete with these DTP prices in their 2026 contracting cycles. To date, those efforts remain conceptual rather than finalized.

For now, watchful waiting remains the prudent approach. At the same time, thoughtful discussions around innovative pricing and access models should absolutely remain on the table. Prism is actively participating in these discussions and helping clients evaluate what is actionable versus what is simply market noise.

Therapies to Watch Following Recent FDA Approvals

In addition to pricing updates, December introduced several FDA approvals that may meaningfully influence future utilization and cost trends across specific therapeutic areas, most notably weight loss, asthma, and antihyperlipidemic therapy (cholesterol).

Wegovy Pill

On December 22, the FDA approved the first oral GLP-1 for weight loss: the Wegovy pill from Novo Nordisk. The oral formulation carries the same 2 core indications as injectable Wegovy for weight management and cardiovascular risk reduction, but was not approved for MASH, which remains specific to the injectable product.

Novo Nordisk plans to launch the pill in early 2026. The starting 1.5 mg dose is expected to be offered at $149 per month via savings programs, though this is a titration dose and not intended for long-term maintenance. Clinical outcomes were driven by the 25 mg dose, where average weight loss reached 16.6%, comparable to injectable Wegovy. The wholesale acquisition cost of the Wegovy pill is currently listed at $1,349 for a 30-day supply. The Wegovy injection carries the same price for a 28-day supply, since a once-weekly injection results in a 4-week package. Looking closely at this, the annual gross cost of Wegovy injection technically ends up $1,349 higher than the pill assuming perfect adherence, because dispensing every 28 days leads to one additional fill each year compared with 30-day supplies.

Because the Wegovy pill is peptide-based, it must be taken on an empty stomach with limited water, followed by a 30-minute wait before eating, drinking, or taking other oral medications. These requirements may pose adherence challenges for some patients and do not apply to injectable GLP-1s.

Competition is coming quickly. Eli Lilly’s oral GLP-1 candidate orforglipron, a non-peptide agent without the same fasting restrictions, is under FDA review and expected to launch in early 2026, with trial data showing ~11.2% average weight loss at 72 weeks.

Exdensur

On December 16, the FDA approved Exdensur (depemokimab) from GlaxoSmithKline, the first ultra-long-acting biologic for severe eosinophilic asthma. Exdensur enters a crowded biologic asthma market that includes Dupixent, Nucala, Xolair, Fasenra, and Cinqair.

The key differentiator with Exdensur is dosing frequency. Exdensur is administered just twice per year, compared with every 2–8 weeks for existing biologics. That convenience comes with trade-offs: Exdensur must be administered by a healthcare provider and cannot be self-injected at home. Medispan lists a wholesale acquisition cost of $26,000 per injection, or $52,000 per year; identical to Dupixent’s annual WAC at maintenance dosing. That said, additional consideration is needed for provider administration costs under the medical benefit for Exdensur.

This approval also refocuses attention on the class overall. Xolair, which ranked second only to Dupixent in asthma biologic spend in 2024, is expected to face biosimilar competition in 2026. Once net pricing is known, plans should be prepared to move quickly to realign coverage toward the lowest net-cost options in the injectable asthma category.

Lerochol

On December 15, the FDA approved Lerochol (lerodalcibep), a third-generation PCSK9 inhibitor positioned to compete with Repatha, Praluent, and Leqvio.

Lerochol is differentiated primarily by its dosing convenience, injection volume, and storage requirements. It is self-administered as a once-monthly, single small-volume subcutaneous injection and remains stable at room temperature for up to 3 months. By comparison, Repatha, the highest-selling PCSK9 inhibitor based on 2024 sales, is administered either every 2 weeks as a single injection that requires a brief warm-up period after refrigeration, or monthly via the Pushtronex device, which delivers 3 sequential injections over approximately 5 minutes.

Early clinical evidence suggests that Lerochol’s LDL-C reduction is at least comparable to, and in some analyses may exceed that of Repatha. However, Repatha currently has more mature long-term cardiovascular outcomes data, and direct head-to-head outcomes trials between the agents have not yet been completed.

While Lerochol pricing has not yet been released, its dosing simplicity and storage profile suggest it may be favored from a patient preference and adherence standpoint once it enters the market.

Hemgenix: Five Year Data and What It Means for Cost and Care

Hemgenix, approved in 2022 as the first gene therapy for hemophilia B, has always raised two big questions: First, does it truly replace long term prophylaxis? Second: if we spend millions upfront, how long before the investment pays off? Recent five-year data from CSL Behring’s HOPE B study, which followed 51 adult males, offers the clearest view yet. Researchers compared patients’ annual bleed rates after a single Hemgenix infusion with baseline rates measured during a six-month observation period prior to treatment. Clinically, the results are compelling. Mean adjusted annual bleed rate fell about 90%, from roughly 4.2 to 0.4. 94% of patients discontinued continuous prophylaxis. Overall factor IX consumption declined by approximately 96% across five years.

This naturally leads to the economic question. Using very simple math and acknowledging this is not actuarial: If factor IX use drops by about 96%, we can assume a similar proportion of factor IX drug cost is avoided. Residual factor use, which is roughly 4% of baseline, should then be added back as ongoing cost. Typical prophylaxis regimens range from $500k to $900k per member per year (gross cost), with $600k often used as a midpoint estimate.

Under those assumptions, Hemgenix begins to look economically viable more quickly for members who were already on the higher end of prophylaxis spending. At year five, some plans could be approaching break even. For members on the lower end of factor IX cost, break even likely shifts closer to years six or seven.

Next steps: a long-term extension study will follow patients out to 15 years. This will be critical for understanding durability, retreatment potential, and the true return on investment.

Of course, cost is only part of the story. Access, preparation, and clinical logistics for gene therapy remain complex and costly. Uptake across the broader gene therapy market has been uneven, and several hemophilia gene therapies have been removed from the market due to lack of use. Many providers and patients also remain comfortable with established non gene therapy options for hemophilia that have delivered reliable outcomes for years.

Even so, the five-year Hemgenix data are encouraging. We see clinically meaningful reductions in bleeding and factor utilization, along with a realistic path to economic value over time, especially in higher cost prophylaxis populations. As durability data mature and payer strategies evolve, Hemgenix will remain an important therapy to monitor in the hemophilia B landscape.