By Beckie Fenrick, PharmD, MBA and Jason Peterson, RPh
Q4 2025 brings meaningful FDA activity across high-cost therapeutic areas, along with notable safety and labeling updates that could shift prescribing patterns. These changes—combined with new generics, updated COVID-19 vaccines, and a steeply discounted Stelara biosimilar—create several points of impact for pharmacy benefit oversight and formulary planning.
Rybelsus (semaglutide) – New Indication
Rybelsus, the oral formulation of semaglutide first approved in 2019 as an adjunct to diet and exercise for type 2 diabetes, received an expanded FDA indication to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who are at high cardiovascular risk. This aligns its cardiovascular-risk reduction indication with injectable semaglutide products Ozempic and Wegovy while maintaining oral administration.
Plan Sponsor Considerations
- Utilization Management: Prior authorization; quantity limits
- Cost Impact: WAC $998 for 30 daily tablets
- Clinical Notes: First oral GLP-1 with a MACE indication; offers the same cardiovascular-risk reduction benefit as injectable semaglutide for patients who cannot or prefer not to use injections
Lynkuet (elinzanetant) – New Approval
Lynkuet is a newly approved non-hormonal therapy for moderate to severe vasomotor symptoms (hot flashes) associated with menopause. In clinical trials, it significantly reduced both the frequency and severity of symptoms compared with placebo, with headache and fatigue reported as the most common adverse events.
Plan Sponsor Considerations
- Utilization Management: Prior authorization; quantity limits
- Cost Impact: WAC $625 for 60 capsules (two daily); alternatives include Veozah (WAC $567/30 days) and Premarin (brand WAC $212; generic WAC $180/30 days)
- Clinical Notes: Non-hormonal option; requires baseline and 3-month liver function testing; alternatives include Veozah (with hepatotoxicity boxed warning) and Premarin (recently had most boxed warnings removed)
Jascayd (nerandomilast) – New Approval
Jascayd is FDA-approved for adults with idiopathic pulmonary fibrosis (IPF), a progressive disease with limited treatment options. In clinical studies—including patients both on and off background antifibrotic therapy using Ofev (46%) or Esbriet (32%)—Jascayd was associated with stabilization of lung function versus placebo.
Plan Sponsor Considerations
- Utilization Management: Prior authorization; renewal criteria based on therapy response
- Cost Impact: WAC $16,220 for 60 tablets (taken every 12 hours); combination therapy annually may exceed $360k with Ofev or ~ $200k with generic Esbriet
- Clinical Notes: More likely to be used as add-on therapy than monotherapy; diarrhea was more common when combined with Ofev (62%) compared with Esbriet (24%) or monotherapy (26%)
Rhapsido (remibrutinib) – New Approval
Rhapsido is approved for adults with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. It is the first oral Bruton’s tyrosine kinase (BTK) inhibitor and the first targeted oral therapy indicated for CSU.
Plan Sponsor Considerations
- Utilization Management: Prior authorization; renewal criteria based on response
- Cost Impact: WAC $4,521 for 60 tablets (taken twice daily); pricing aligns with Dupixent and is ~30% higher than Xolair
- Clinical Notes: First targeted oral therapy for CSU; meta-analysis shows similar effectiveness and side-effect profile to Dupixent and Xolair; oral administration may be preferred over injectables
Updated COVID-19 Vaccine Formulations
For the 2025–2026 season, the FDA approved updated formulations of Comirnaty, Spikevax, mNEXSPIKE, and Nuvaxovid that target currently circulating variants. These vaccines are now fully or supplementally approved for adults 65 and older and for younger individuals with qualifying risk factors, and prior Emergency Use Authorizations were rescinded as part of the update.
Removal of Boxed Warnings for HRT
In November 2025, the FDA announced it will remove most boxed (“black box”) warnings from hormone replacement therapy medicines used for menopause symptoms. Earlier warnings highlighted risks such as heart disease, breast cancer, and dementia based on older research, but newer evidence shows these risks are much lower for most women; the FDA is working with manufacturers to update labels to better reflect current risk–benefit information, while a boxed warning for endometrial cancer will remain on estrogen-only products.
Select Generic Launches
| Brand Name | Generic Name | Generic WAC | Discount to Brand WAC | Launch Date | Comments |
| Mavenclad | cladribine | $8,843.50/tab | 20% | 11/25/2025 | Only 1 generic competitor launched with 4 additional manufacturers expected to enter the market. |
| Ravicti | glycerol phenylbutyrate | $185.22/ml | 22% | 10/20/2025 | 2 generic competitors launched with 4 additional manufacturers expected to enter the market. |
| Premarin (tablets) | estrogens conjugated | $6.01/tab | 15% | 10/17/2025 | Only 1 generic competitor launched with 1 additional manufacturer expected to enter the market. |
| Endometrin | progesterone | $13.27ea | 10% | 09/23/2025 | Only 1 generic launched and no additional manufacturers are expected to enter the market. |
| Adzenys XR-ODT | amphetamine | $17.34 | 14% | 09/02/2025 | Only 1 generic competitor with 2 additional manufacturers expected to enter the market. |
Select Biosimilar Launch: Starjemza (interchangeable with Stelara)
Starjemza, an interchangeable biosimilar to Stelara, launched at the largest list price discount to Stelara’s WAC to date: the 90 mg/mL strength is priced at $500 per syringe (a 98% discount to Stelara), and the 45 mg/0.5 mL strength at $440 (a 97% discount to Stelara). Even lower pricing is available through Mark Cuban Cost Plus Pharmacy, where both strengths are $360 per syringe plus $55 for next-day refrigerated shipping.
Final Thoughts on the Q4 2025 Drug Landscape
The approvals, label changes, and market entrants in Q4 2025 highlight areas where cost, utilization, and clinical guidance may shift in the coming year. Monitoring these developments—and adjusting formulary and UM strategy as needed—will be key to supporting appropriate access while managing pharmacy spend.
If you’re evaluating how these developments may shape your 2026 pharmacy benefit strategy, reach out to Navion to continue the conversation.
