dm+d

Unassigned

New Medicines

TepezzaThyroid eye disease (Graves orbitopathy); active, moderate-to-severe

Information

Tepezza
New molecular entity
Horizon Therapeutics
Horizon Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase III Clinical Trials
Launched
Yes
Jun 21Company webinar presentation reports plans to expand Tepezza to Europe, starting the regulatory process Q1 2022 as well as plans to expand use to chronic TED and develop a subcutaneous formulation [22]
Jun 21Company reports uptake of Tepezza in the US has risen in recent months, following disruptions due to COVID. Horizon management noted that 75% of disrupted patients had either restarted or were scheduled to resume treatment versus a 50% figure from the previous month. A leading expert in the US reported significant amounts of interest in the treatment from patients but sees price as a potential hurdle to its use, as well as side effects with around 80% of his patients reporting side effects, most commonly muscle cramps, nausea and diarrhoea. Success of Tepezza may affect recruitment into trials of other potential treatments, such as RVT-1401 [21].
Jun 21Company is currently focussing on development in US and Japan. No indication of plans for Europe [20]
Nov 20Company presentation reports they are "Pursuing global expansion to provide TEPEZZA to patients with TED in other parts of the world" following "Significantly higher TEPEZZA net sales expectations of >$800M (previously >$650M)" in the US. A subcutaneous formulation is also being investigated as well as potential in other diseases, e.g. diffuse cutaneous systemic sclerosis [19].
Nov 20Offers an alternative to steroids and surgery that returns the eyeball to a normal position in the eye socket. Horizon believes the complexity of manufacturing Tepezza could pose a barrier to potential biosimilar competition [14]. On announcement of US approval, FDA spokesperson said "approval marks an important milestone for the treatment of thyroid eye disease. Currently, there are very limited treatment options for this potentially debilitating disease. This treatment has the potential to alter the course of the disease, potentially sparing patients from needing multiple invasive surgeries by providing an alternative, non surgical treatment option" [16].
Jun 20Launched in the US Q1 2020 [17]
Jan 20Horizon priced its treatment for thyroid eye disease at $14,900 per vial following the U.S. FDA approval and said the drug would be available in the US in the coming weeks [15].
Jan 20Approved in US [12].
Dec 19All 12 members of an FDA advisory committee voted to recommend the approval of teprotumumab. [11]
Sep 19Granted priority review in US with a PDUFA goal date of 8/3/20 [10].
Jul 19Horizon Therapeutics file BLA for the treatment of active thyroid eye disease US [9].
Mar 19Horizon expects to submit NDA to FDA in mid 2019 [6]; (no info about any EU application)
Mar 18Has orphan drug status, breakthrough therapy status and fast track status in the US [4].
Mar 18Genmab is collaborating with Horizon Pharma in developing teprotumumab [2].

Category

A fully human IgG1k monoclonal antibody (mAb) that binds to insulin-like growth factor-1 (IGF-1R)
Thyroid eye disease is the most common cause of orbital inflammation and proptosis in adults. It affects an estimated 400,000 people in the UK, a prevalence of 0.7% [1].
Thyroid eye disease (Graves orbitopathy); active, moderate-to-severe
Intravenous infusion

Trial or other data

Oct 21Results of OPTIC-X published in Ophthalmology. Patients treated with teprotumumab had a high rate of maintained response at week 48 (27 weeks after last dose): 91.7% for overall response, 90.6% for proptosis, 85.7% for diplopia [23].
Apr 21Pooled data analysis, subgroup analysis, and off-treatment follow up results from two randomised, double-masked, placebo controlled, multicentre trials of adults with active thyroid eye disease (n=171), found more patients receiving teprotumumab than placebo achieved a proptosis response (77% v 15%, number needed to treat 1.6; primary endpoint), diplopia response (NNT 2.5) and overall response (NNT 1.7) at 24 wks [21].
Nov 20Horizon Therapeutics announced new data presented at the American Academy of Ophthalmology Annual Meeting, including findings suggesting benefits of teprotumumab in the less severe eye of patients with Thyroid Eye Disease (TED), and new data from the OPTIC 48-week follow-up study and OPTIC-X clinical trial, with findings showing that the majority of teprotumumab patients who were diplopia responders in OPTIC at week 24 maintained their response at week 72. Patients who received placebo during the OPTIC PIII trial and then received teprotumumab in the OPTIC-X extension trial also achieved clinically significant diplopia improvement with an average of 12 months of disease, vs 6 months in OPTIC [20]
Jan 20PIII OPTIC trial (NCT03298867; n=83) is published in the NEJM; it found teprotumumab resulted in better outcomes for proptosis at week 24 (primary outcome) than placebo (proptosis response of 83% [n=34] vs. 10% [n=4], p<0.001), respectively) and for Clinical Activity Score, diplopia, and quality of life; serious ADRs were uncommon [13].
Sep 19Horizon Pharma announce early completion of the PIII OPTIC trial. The study (NCT03298867; EudraCT 2017-002763-18) enrolled 83 patients at 13 sites across the US, Germany and Italy. Topline results are expected Q2 2019 [5].
Apr 19Further results from the PIII OPTIC trial were presented at the 2019 American Association of Clinical Endocrinologists (AACE) Scientific and Clinical Congress. The new data were from 2 secondary endpoints. Throughout the 24 week treatment period, patients treated with teprotumumab had an average proptosis reduction of 2.82 mm vs 0.54 mm for placebo (p<0.001). There was a significant difference in proptosis reduction from baseline between teprotumumab and placebo at all study time points: Week 6 (-2.00 mm vs. -0.38), Week 12 (-2.70 vs. -0.64), Week 18 (-3.26 vs. -0.59) and Week 24 (-3.32 vs. -0.53). Patients treated with teprotumumab had an overall responder rate of 78% vs 7.1% in the placebo group at week 24 (p<0.001). Overall response rate to teprotumumab was significantly better than placebo from baseline at all study time points: Week 6 (43.9% vs. 4.8%), Week 12 (63.4% vs. 11.9%), Week 18 (73.2% vs 11.9%) and Week 24 (78.0% vs. 7.1%). An extension trial OPTIC‐X (NCT03461211) is ongoing [8].
Feb 19Horizon Pharma announce topline results from PIII OPTIC trial. In trial (n=83), more patients treated with teprotumumab vs. placebo, had a meaningful improvement in proptosis (bulging of eye): 82.9 vs 9.5% achieved primary endpoint of ≥2 mm reduction in proptosis (p<0.001) [7].
Mar 18PIII trial to assess the efficacy, tolerability, and safety of teprotumumab in patients with Graves ophthalmopathy start (OPTIC; NCT03298867). The primary endpoint will measure the proptosis responder rate of ≥ 2 mm reduction of proptosis in the study eye (without deterioration in the fellow eye) at week 24. 76 patients will be enrolled in the US, Germany and Italy . Collection of primary outcome data is expected to complete Jun 19 [3].
May 17PII study published in NEJM. Teprotumumab met its primary and secondary endpoints in patients with active phase Graves´ ophthalmopathy (NCT01868997). 88 patients were randomised to receive teprotumumab (10 mg/kg first infusion, then 20 mg/kg for remaining seven infusions administered every 3 weeks over 6 months) or placebo (total eight infusions, every 3 weeks over 6 months) in the US, Germany, Italy, Netherlands and the UK [4].

Evidence based evaluations