September 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.
September Policy Shake-Up: MFN and Tariffs
September was anything but quiet in Washington when it comes to drug policy. Two storylines grabbed the spotlight: the long-anticipated deadline for President Trump’s Most Favored Nation (MFN) Executive Order and a surprise announcement of 100% tariffs on branded drugs. Let’s unpack what happened and what it means.
MFN: A Summer of Deadlines
September 29 marked the day manufacturers had to respond to President Trump’s MFN push. A quick recap:
- May 12, 2025 – The original EO pushed to tie U.S. drug prices to the lowest prices in other developed nations, signaling potential disruption to PBM rebate structures and renewed attention on direct-to-patient (DTP) models.
- July 31, 2025 – Letters went out to 17 drugmakers, laying out four requirements with a 60-day ultimatum: MFN pricing for Medicaid, no better prices abroad, direct-to-patient sales at MFN price levels, and trade support linked to U.S. price cuts.
What have we seen since? A handful of manufacturers launched cash-pay, direct-to-patient programs. On September 29, President Trump also touted a deal with Pfizer to provide discounted drugs to Medicaid plus a handful of products via the DTP route (more on this in the next section of the newsletter). Meanwhile, PhRMA, the industry trade group, offered its own proposal, seemingly on behalf of the broader industry, stating manufacturers would commit to:
- $500 billion in U.S. infrastructure investments, with 100,000+ jobs on the way (including 25,000 in biopharma).
- Expanded patient assistance programs, with an emphasis on the Medicine Assistance Tool (MAT) to help patients easily locate financial assistance.
- A new hub, AmericasMedicines.com, is set to launch January 2026 to connect patients with manufacturer direct-to-patient programs.
At this point, we can speculate, but perhaps more confidently than we could at the beginning of the summer, as the landscape rapidly changes: expect more direct-to-patient offerings from big pharma as they try to balance White House pressure with business realities.
Tariffs: Big Headline, Smaller Impact
On September 29, President Trump also announced a 100% tariff on imported branded and patented drugs that was expected to start October 1. The president quickly reversed course on October 1 and announced he would be delaying these tariffs as the White House engages in conversations with manufacturers over the coming weeks. Between MFN and the threat of tariffs, the common thread is clear: Washington wants drugmakers to lean harder into U.S. pricing concessions and direct-to-patient access. For plan sponsors, this could eventually reshape rebate structures, pricing models, and how patients access therapies.
TrumpRx and the Ever-Evolving Direct-to-Patient Market
As a follow-up to the September policy developments, it’s important to address the latest wave of direct-to-patient announcements. Manufacturers are increasingly testing DTP models outside of traditional PBM channels. Over the past several weeks, Bristol Myers Squibb (BMS), Novartis, and Pfizer have each expanded into this space, signaling momentum behind cash-based pricing strategies aimed at transparency and “lowest net cost” positioning.
Bristol Myers Squibb: Expanding from Eliquis to Sotyktu
- Eliquis entered the BMS DTP program in July at 40% below list price, aligning the cash price with typical PBM net costs after rebates.
- Sotyktu (for plaque psoriasis) will join the program in January 2026 at a cash price of $950 per 30-day supply. This reflects an 86% discount off WAC and a 66% reduction versus current estimated net cost post-rebate. Copay assistance is available, but BMS has not publicly disclosed an annual maximum. To reach a $950 net price through PBM channels, plans would require an estimated $22,000 in copay support annually in addition to rebates.
Novartis: Cosentyx DTP Launch
- Effective November 1, Novartis will introduce Cosentyx (psoriasis and other inflammatory conditions) as its first DTP product.
- The program offers a 55% discount off WAC, yielding an estimated cash price of $3,571 per month.
- By comparison, PBM rebates for Cosentyx currently average 50–55% off WAC. For many plan sponsors, PBM net costs may be similar or lower once factoring in Novartis’s $16,000 annual copay assistance program.
Pfizer: TrumpRx Partnership
In a landmark agreement announced on September 30, Pfizer committed to offering many of its medicines via a new direct-to-patient platform, TrumpRx.gov, at deep discounts, with savings ranging up to 85% and averaging roughly 50%. The deal also includes a three-year grace period during which Pfizer products will not face tariffs tied to Section 232 investigations (provided Pfizer continues investing in U.S. manufacturing) and requires that Pfizer price newly launched medicines in the U.S. in line with prices in other developed countries (i.e. “most-favored-nation” pricing). Under this framework, the sliding scale of discounts offered through TrumpRx complements the discounts already being proposed under the White House MFN approach.
The September 30 White House MFN fact sheet highlighted three Pfizer therapies that will be available through discounted DTP pricing:
- Eucrisa (atopic dermatitis): 80% discount for direct purchasers. PBM rebates typically 55–60% discount off WAC. Copay assistance: $3,800 annually.
- Xeljanz (rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, others): 40% discount for direct purchasers. PBM rebates average 45–50% discount off WAC. Copay assistance: $4,000–$15,000 annually, depending on insurance.
- Zavzpret (migraine): 50% discount for direct purchasers. No reliable PBM rebate estimates or copay assistance data currently available.
Key Takeaways for Plan Sponsors
These programs highlight a trend toward greater transparency and alternative distribution models. However, a critical issue remains unresolved: utilization management. Current DTP programs do not include clinical oversight mechanisms, which are traditionally handled by PBMs and are particularly important for specialty and high-cost therapies. Without such safeguards, DTP may serve less as a direct replacement for PBM-managed access and more as a tool for highlighting the true economics of drug pricing.
Plan sponsors should view these developments as a signal of what may come. While the immediate impact on benefit design is limited, the expansion of DTP programs reinforces the need to evaluate strategies around net cost, manufacturer assistance, and clinical appropriateness. That said, these DTP programs will likely be most impactful for uninsured or underinsured patients, at least in the near term.
Ocaliva Pulled from Market Following FDA Safety Concerns
On September 11, Intercept Pharmaceuticals announced that it would be removing its primary biliary cholangitis (PBC) therapy, Ocaliva, from the market. Ocaliva was first approved by the FDA nine years ago but has faced ongoing safety concerns throughout its life cycle. In 2021, it received a contraindication for use in patients with advanced cirrhosis, and in 2024, the FDA issued a safety alert linking the drug to serious liver injury in PBC patients without cirrhosis.
Ocaliva received accelerated approval in 2016, meaning the approval was granted based on surrogate endpoints rather than direct evidence of clinical benefit, with the expectation that confirmatory trials would follow. A surrogate endpoint is a stand-in measurement, such as a lab test or biomarker, that researchers use to predict whether a treatment will help patients live longer or feel better. Because these measures do not prove real clinical benefit on their own, drugs approved using surrogate endpoints can only receive accelerated approval until confirmatory studies are completed. In November 2024, the FDA denied Intercept’s bid for full approval, citing an unfavorable benefit risk profile. By August 2025, the FDA requested the drug’s removal from the market and placed all ongoing clinical trials on hold.
Primary biliary cholangitis is a chronic autoimmune liver disease marked by destruction of the bile ducts in the liver, leading to inflammation, scarring, and eventual liver failure. Ursodiol has long been considered first line therapy and was originally FDA approved as Urso 250 in 1997. It is currently the only product available with full FDA approval for PBC; however, it is often not as effective as the newer brand products. In 2024, two new agents, Iqirvo and Livdelzi, received accelerated approval using the same surrogate endpoints as Ocaliva. Unlike Ocaliva, these therapies work through different mechanisms of action and to date have not demonstrated the same safety risks.
From a cost perspective, generic ursodiol remains the most affordable option at about $500 per year. In contrast, Ocaliva carried a wholesale acquisition cost of $116,241 annually, while Livdelzi’s is $153,373 and Iqirvo’s is $139,430. For patients who now must transition away from Ocaliva, cost will be a factor, but clinical benefit may be the deciding point. Both Livdelzi and Iqirvo have demonstrated strong efficacy in terms of biochemical response, yet Livdelzi showed a statistically significant improvement in pruritus (itching), a common and burdensome symptom in PBC. This advantage makes Livdelzi the more clinically compelling of the two, while Iqirvo may be a reasonable choice in situations where price or patient specific safety considerations guide decision making.
Bisphosphonates Show Survival Advantage Beyond Bone Health
A new real-world study presented at the American Society for Bone and Mineral Research annual meeting highlights an important development in osteoporosis management. Researchers found that bisphosphonates, including alendronate (Fosamax) and ibandronate (Boniva), were linked to a lower risk of death following a low trauma fracture when compared with denosumab (Prolia). In adults aged 50 and older who experienced fractures, survival probabilities at 48 months post fracture were 24.4% higher in men and 28.1% higher in women on bisphosphonates. While refracture free survival rates were similar between the two treatment groups, bisphosphonates were associated with lower all-cause mortality, particularly in patients with cardiometabolic conditions such as hypertension and diabetes, geriatric conditions such as dementia and neurological disorders, and complex cardiovascular conditions such as heart failure, chronic kidney disease, and arrhythmias. Since more than 60 percent of fractures occur in individuals with comorbidities, these findings emphasize the importance of evaluating osteoporosis therapies not only for their impact on bone health but also for their broader effects on overall survival.
For plan sponsors and healthcare professionals, this study reinforces the long-standing role of bisphosphonates as first line therapy. In addition to strong efficacy and extensive safety data, generics remain highly affordable with costs often under $50 per year. In contrast, Prolia and its current biosimilars average about $3,000 annually for the drug itself, with additional medical costs tied to administration by a healthcare professional. Even though biosimilar prices are expected to decrease by at least 50% with the introduction of Bildyos in late 2025 or early 2026, the cost difference remains substantial. When combined with evidence suggesting broader survival benefits, bisphosphonates stand out as a highly cost effective and convenient option for many patients with osteoporosis.
