First oral GLP-1 drug for weight loss

In our latest edition of this ongoing series to highlight anticipated new drugs, we’ll review:

• Wegovy® (semaglutide) in a new oral formulation for chronic weight management and to reduce the risk of major adverse cardiovascular events (MACE).
• Depemokimab for severe asthma and chronic rhinosinusitis (inflammation of the nasal and sinus passages) with nasal polyps.
• Remibrutinib for chronic spontaneous urticaria, a skin condition with repeated, spontaneous hives and/or swelling.

These drugs treat chronic conditions and are expected to receive Food and Drug Administration (FDA) approval before the end of 2025.

The Optum Rx drug pipeline and surveillance team continuously monitors and evaluates medications in development and shares important details on upcoming drug approvals.

Please refer to our 3rd quarter Rx Outlook report for additional technical background and supplemental sources.

Expected FDA decision: 4th Quarter 2025 

Therapeutic use
Overweight and obesity are very common in the U.S., with 74% of the adult population overweight, including 40% living with obesity. 

The FDA is reviewing a new oral formulation of Wegovy for chronic weight management, which could make it the first oral GLP-1 receptor agonist approved for weight loss. Currently, the only oral formulation of a GLP-1 receptor agonist is Rybelsus® (semaglutide), which is approved for type 2 diabetes.

This formulation is intended for adults who are overweight or obese with one or more associated conditions. It’s also being studied for the ability to reduce the risk of serious cardiovascular events (also referred to as MACE) in adults with established cardiovascular disease.

Competitive environment

Wegovy would be the first GLP-1 receptor agonist that can be taken orally for chronic weight management or weight loss. It would be competing with Novo Nordisk’s own injectable semaglutide and Eli Lilly’s injectable tirzepatide (Zepbound®). It would be a potential option for patients who prefer daily oral medications over injectable products (e.g., patients suffering from needlephobia). Weight loss effectiveness and side effect risks for oral Wegovy are comparable to the injectable formulation.

In addition to other injectable products, oral Wegovy would also be competing with Eli Lilly’s pipeline oral GLP-1 receptor agonist, orforglipron. In recent trials, orforglipron demonstrated superior weight loss vs. placebo. Eli Lilly is expected to file for approval later this year, with potential approval in 2026. 

For reference, the estimated wholesale acquisition cost for injectable Wegovy is approximately $16,000 per year. As Rybelsus® (oral semaglutide for type 2 diabetes) and Ozempic® (injectable semaglutide for type 2 diabetes) have similar pricing, it’s likely that oral Wegovy would be priced similarly to the injectable formulation.

Expected FDA decision: December 16, 2025

Therapeutic use
Depemokimab is under review for add-on maintenance treatment of eosinophilic asthma, a rare subtype of asthma, in patients age 12 years and older with type 2 inflammation. Additionally, depemokimab is under review as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyps.

Asthma is a chronic lung disease that can cause shortness of breath, chest tightness and coughing. Uncontrolled symptoms (or exacerbations) can result in hospitalization and life-threatening complications. Asthma affects approximately 26.8 million adults and 4.5 million children in the U.S. About 5% to 10% of patients have severe asthma, including eosinophilic asthma. These patients are typically difficult to treat despite available inhaled therapies.

Chronic rhinosinusitis with nasal polyps causes inflammation of the nasal and sinus passages with nasal polyps, leading to symptoms like facial pain/pressure, loss of smell (hyposmia/anosmia), nasal drainage and nasal obstruction. Chronic rhinosinusitis affects 2.1% of the U.S. population and nasal polyps develop in about 30% of cases.

Competitive environment

Asthma is typically treated with inhaled corticosteroids and other maintenance therapies, such as inhaled long-acting beta 2 agonists. Many of the standard of care inhaler treatment options are available generically as single-ingredient drugs and combination products. 

In patients with continued uncontrolled asthma, several injectable biologic products have been approved, including Nucala® (mepolizumab), Fasenra® (benralizumab) and Cinqair® (reslizumab). Other biologics are also used, including Dupixent® (dupilumab) and Tezspire® (tezepelumab).

Chronic rhinosinusitis with nasal polyps is typically treated with intranasal corticosteroids. Like asthma, uncontrolled chronic rhinosinusitis can be treated with injectable biologics, including Dupixent®, Nucala® and Xolair® (omalizumab).

Depemokimab achieved treatment goals in clinical trials but has not been compared head-to-head against the biologic drug alternatives for both eosinophilic asthma and chronic rhinosinusitis with nasal polyps. Notably, depemokimab is administered every six months, whereas the current biologic treatment options require injections every four to eight weeks. However, depemokimab will need to be administered by a healthcare provider, while alternatives may be self-administered.

For reference, the wholesale acquisition cost for Nucala, the only other similar drug approved for both asthma and chronic rhinosinusitis, is approximately $46,000 per year.

FDA approved: September 30, 2025

Therapeutic use
Remibrutinib is intended for adults with chronic spontaneous urticaria, a skin condition with repeated, spontaneous hives and/or swelling that lasts six weeks or more. 

Chronic spontaneous urticaria affects about 1.7 million people in the U.S. It is seen in women twice as commonly as men, and is more common in patients between 20 to 40 years of age.

Remibrutinib is a potential oral alternative to injectable biologics such as Dupixent® (dupilumab) and Xolair® (omalizumab). 

Competitive environment

Chronic spontaneous urticaria is treated with second-generation H1-antihistamines, which are available as over-the-counter products and generic prescriptions. However, about 50% of patients continue to have symptoms while receiving H1-antihistamines. Second-line therapy includes injectable biologics, Genentech’s Xolair® (omalizumab) and Regeneron/Sanofi’s Dupixent® (dupilumab). Biosimilar competition is expected for Xolair in the second half of 2026.

Remibrutinib would provide a novel mechanism of action for the treatment of chronic spontaneous urticaria and an oral alternative to injectable products in patients who have failed first-line antihistamines. It works by blocking a specific chemical cascade to prevent the release of histamine that causes itch, hives/welts and swelling. 

The efficacy for remibrutinib appears promising, with a rapid onset of action, but there are no head-to-head trial comparisons against injectable biologics.

While this class of inhibitors has historically been associated with liver toxicity, elevated toxicity signals were rare and transient with remibrutinib, and it was generally well-tolerated in the trials.

Initial indication for remibrutinib would be limited to adults (18+ years), targeting a smaller population than Xolair and Dupixent, which are both approved for patients 12 years and older and for a range of other indications.

Remibrutinib is also in development for multiple other indications, including hidradenitis suppurativa, myasthenia gravis, and multiple sclerosis. These would be unique indications compared to Xolair and Dupixent, but each of those conditions has other treatment options currently available.

For reference, the wholesale acquisition cost for Dupixent, the latest drug approved for chronic spontaneous urticaria, is approximately $48,000 per year.