How does Lumvoa (veligrotug‑vvze) compare to Tepezza (teprotumumab) for treating thyroid eye disease?

Lumvoa and Tepezza Are Essentially Equivalent Treatment Options for Thyroid Eye Disease

Both Lumvoa (veligrotug) and Tepezza (teprotumumab) are FDA-approved IGF-1R inhibitors with identical indications for treating thyroid eye disease regardless of activity or duration, and current evidence suggests they deliver comparable clinical outcomes. 1, 2

Mechanism of Action

Both drugs function as monoclonal antibodies targeting the insulin-like growth factor-1 receptor (IGF-1R), which forms a complex with the thyrotropin receptor—a key driver of TED pathogenesis. 3 However, there is a critical pharmacologic distinction:

• Veligrotug (Lumvoa) acts as a full antagonist, providing near-complete inhibition of IGF-1 binding (≥50 nM) and near-complete blockade of IGF-1R autophosphorylation and AKT phosphorylation 4
• Teprotumumab (Tepezza) functions as a partial antagonist, plateauing at approximately 50% inhibition of IGF-1 binding 4

The two drugs have overlapping but distinct binding epitopes on the IGF-1R. 4

Clinical Efficacy: Head-to-Head Comparison

Lumvoa (Veligrotug) - THRIVE Trial Data

The Phase 3 THRIVE trial demonstrated robust efficacy at week 15 with only 5 infusions (versus 8 for Tepezza): 5

• Proptosis response rate: 70% vs 5% placebo (p<0.001)
• Mean proptosis reduction: 2.90 mm (Hertel) and 2.96 mm (MRI/CT)
• Diplopia improvement: 59% vs 20% placebo
• Diplopia resolution: 49% vs 12% placebo
• Overall response rate: 67% vs 5% placebo
• Durability: 70% of responders maintained response at week 52
• Treatment discontinuation: Only 4%

Tepezza (Teprotumumab) - Pooled Phase 2/3 Data

The pooled analysis of two RCTs with 8 infusions showed: 6, 3

• Proptosis response rate: 77% vs 15% placebo (p<0.0001)
• Mean proptosis reduction: 3.14 mm from baseline
• Diplopia improvement: 70% vs 31% placebo (53% complete resolution)
• Overall response rate: 74% vs 14% placebo
• Disease inactivation: 62% vs 22% placebo
• Durability: 67% maintained proptosis response at 51 weeks post-treatment

Practical Clinical Differences

Dosing Regimen

• Lumvoa: 5 infusions over 12 weeks (10 mg/kg first dose, then 20 mg/kg every 3 weeks) 5
• Tepezza: 8 infusions over 21 weeks (10 mg/kg first dose, then 20 mg/kg every 3 weeks) 3

This represents a significant practical advantage for Lumvoa—fewer infusions, shorter treatment duration, and potentially lower cost.

Safety Profile

Lumvoa (THRIVE trial): 5

• Generally well tolerated
• Most adverse events mild and resolved
• No serious treatment-related adverse events
• 4% discontinuation rate

Tepezza (pooled data): 6, 7

• Muscle spasms: 25%
• Nausea: 17%
• Alopecia: 13%
• Diarrhea: 13%
• Hearing impairment: 10% (potentially devastating and requires frequent monitoring)
• Hyperglycemia: 8%
• Fatigue: 10%
• 4% serious adverse events related to treatment

Critical caveat: Ototoxicity with Tepezza has emerged as a major concern requiring audiometric monitoring. 8 Lumvoa's hearing safety profile appears more favorable based on initial data, though longer-term surveillance is needed.

Contraindications

Both drugs are contraindicated in:

• Inflammatory bowel disease
• Pregnancy 7

Clinical Decision Algorithm

For active moderate-to-severe TED (CAS ≥3):

1. First-line choice: Either Lumvoa or Tepezza based on availability and insurance coverage

   • Favor Lumvoa if: Patient prefers shorter treatment course (5 vs 8 infusions), cost is a consideration, or hearing concerns exist
   • Favor Tepezza if: More extensive long-term safety data is desired (approved since 2020 vs 2026)

2. Both drugs work across disease spectrum: Despite original trial enrollment criteria requiring active disease, both are FDA-approved for TED "regardless of activity or duration" 1, 2

3. Chronic/inactive TED: Tepezza has demonstrated efficacy in longstanding disease (2-10 years duration, CAS ≤1) with -2.41 mm proptosis reduction vs -0.92 mm placebo 9. Lumvoa data in chronic disease is emerging.

4. Recalcitrant disease: Tepezza shows 85.9% proptosis response and 93.8% CAS response in patients who failed prior therapy 10. Lumvoa data pending.

Important Caveats

• Neither drug has been compared to each other or to established treatments (IV steroids, orbital radiation, surgery) in head-to-head trials 8
• Approximately one-third of patients lose benefit by 51 weeks post-treatment with either drug 3
• Prior orbital decompression surgery reduces response rates to Tepezza (46.7% diplopia response vs 77.5% in surgery-naïve patients) 10
• Cost considerations: Tepezza costs approximately $360,000 for full treatment course; Lumvoa pricing likely similar but with fewer infusions 8
• Long-term safety data is more robust for Tepezza (approved 2020) versus Lumvoa (approved 2026)

Bottom Line

Choose Lumvoa for shorter treatment duration (5 vs 8 infusions) and potentially better hearing safety profile, or choose Tepezza for more extensive long-term safety data and proven efficacy in chronic/recalcitrant disease. Both deliver clinically meaningful improvements in proptosis (approximately 3 mm reduction), diplopia, and disease activity with similar overall response rates around 70%. The full antagonist properties of Lumvoa may theoretically provide more complete IGF-1R blockade, but clinical outcomes appear equivalent. Monitor hearing function with either drug, avoid in inflammatory bowel disease and pregnancy, and counsel patients that approximately one-third may require retreatment or lose benefit over time.