Amgen released positive topline findings from a phase 3 clinical trial evaluating TEPEZZA (teprotumamb-trbw) administered as a subcutaneous injection for the treatment of moderate-to-severe active thyroid eye disease (TED).
Hold up … isn’t TEPEZZA already commercially available?
Indeed, it is. In fact, the therapy first received FDA approval in 2020 as the first and only treatment indicated for TED. And since then, updates have included:
- An expansion of its indication
- An update to its prescription warning label
- Real-world data supporting its use for dysthyroid optic neuropathy
- Positive phase 4 data for its use in patients with chronic / low clinical activity score (CAS) TED
- Additional phase 4 data supporting its extended use for TED
So what’s this new data regarding?
Keep in mind: In its current approved form, TEPEZZA is administered as an intravenous (IV) injection in the arm.
- Its dosing frequency: Every 3 weeks for eight infusions
In this new phase 3 data, TEPEZZA was administered as a subcutaneous (SC) injection via an on-body injector (OBI).
- Its proposed dosing frequency: (Potentially) every 2 weeks for 12 injections
- This is still investigational
Ahh, gotcha. Alrighty then — tell me about this phase 3 trial.
Initiated in 2024, this is a randomized, double-masked, placebo-controlled, parallel-group, multicenter trial (NCT06248619).
Its purpose: To evaluate the safety and efficacy of SC TEPEZZA versus placebo among patients with active TED. Other details include:
- The participants: 89 patients (ages 18-90) with TED and a CAS ≥ 3 mm at baseline
- See here for more criteria.
- The setup: Patients received SC TEPEZZA or a placebo via an OBI every 2 weeks for a total of 12 injections.
And what was measured?
The primary outcome was proptosis responder rate (PRR), as measured by the percentage of participants with a ≥2-mm reduction from baseline in proptosis in the study eye without deterioration [≥2-mm increase] of proptosis in the fellow eye at Week 24.
Secondary outcomes (also measured at Week 24) included:
- Mean change from baseline in proptosis measurement in the study eye
- Overall responder rate
- Percentage of patients with a CAS value of 0 or 1.
- Diplopia responder rate
See here for the full list.
Next up: the findings.
For starters, the study met its primary endpoint in demonstrating a statistically significant and clinically meaningful 77% proptosis response rate during its 24-week placebo-controlled period:
- 76.7% TEPEZZA OBI vs 19.6% placebo (p < 0.0001)
And what was the mean reduction in proptosis?
This secondary endpoint clocked in at -3.17 mm at week 24 (-3.17 mm TEPEZZA OBI vs -0.80 mm placebo; p<0.0001).
How did the other secondary outcomes fare?
Amgen reported “statistically significant and clinically meaningful improvements” across the other endpoints:
- Overall responder rate
- Percentage of patients achieving a CAS of 0 or 1
- Changes in diplopia (as ordinal response categories)
- DRR and complete DRR
To note: While another secondary outcome—the mean change from baseline in week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) appearance subscale—was not statistically significant, Amgen reported a “numerical trend favoring TEPEZZA OBI.”
Sounds promising … now let’s talk safety.
In general, TEPEZZA OBI’s safety results were "generally consistent” with its pre-established safety profile in IV form, although some patients experienced mild-to-moderate injection site reactions.
- Notably: These reactions did not impact their treatment.
Among the most common adverse events (occurring in ≥10%):
- Muscle spasms
- Tinnitus
- Weight decrease
- Ear discomfort
- Nausea
- Diarrhea
So! What were the takeaways from this data?
The results indicate a promising potential for expanding TEPEZZA’s administration options with comparable efficacy to its standard IV method—though the dosing frequency will differ and is still under investigation.
In the meantime, we’ll be staying tuned for more developments from Amgen on this front (including a more detailed data readout in the near future).