Tepezza authorized in UK

Amgen announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for Tepezza (teprotumumab) as the first targeted therapy specifically licensed for the treatment of adult patients with moderate-to-severe Thyroid Eye Disease (TED). TED affects approximately 50,000 people in the UK. It is a frequently misdiagnosed and debilitating autoimmune condition that can lead to vision impairment, eye pain and changes in facial appearance. TED is a progressive and potentially vision-threatening condition, which can cause eye bulging, double vision,  redness and swelling. People living with TED often experience anxiety and depression, concerns about their facial appearance and a loss of confidence. This can impact their ability to work, socialise and maintain relationships

Teprotumumab’s marketing authorisation in the UK is supported by multiple clinical studies, including the Phase III clinical trial, OPTIC (n=83). Other clinical studies that supported the marketing authorisation in the UK include the TED01RV Phase II clinical study (n=88), the HZNP-TEP-403 Phase IV clinical study (n=62), and the OPTIC-J Phase III study in Japan (n=54). In the OPTIC trial, teprotumumab demonstrated a statistically significant improvement in the primary endpoint, proptosis (eye bulging) responder rate at 24 weeks, with 83% (34/41) of patients demonstrating a reduction of at least 2mm compared to baseline, versus 10% (4/42) of patients treated with placebo (difference of 73%, 95% confidence interval, 59 to 88; P=<0.001]).

The safety data for teprotumumab is based on multiple clinical studies. The most common side effects observed in these clinical trials are muscle spasms (27.6%), diarrhoea (14.5%), hearing impairment (13.8%), alopecia (13.2%), hyperglycaemia (13.2%), fatigue (12.5%), nausea (10.5%), headache (10.5%), dry skin (9.9%), dysgeusia (8.6%), Covid-19 (6.6%), ear discomfort (6.6%) and nail disorder (5.9%).

Amgen will work with the National Institute for Health and Care Excellence (NICE) to seek reimbursement of teprotumumab for all eligible patients.

"The marketing authorisation for teprotumumab as the first therapy specifically licensed for Thyroid Eye Disease (TED) in the UK marks a step forward for the patient community,” said Dr Tony Patrikios, Executive Medical Director, Amgen UK & Ireland. “TED can negatively affect patients’ lives impacting vision, causing eye pain, making everyday tasks difficult and causing a loss of self-confidence. This authorisation introduces a new alternative treatment option and reinforces Amgen’s commitment to supporting eligible patients with serious, underserved conditions.”

“For adult patients living with Thyroid Eye Disease (TED), it can be challenging to receive a diagnosis and referral to specialist centres. TED is often mistaken for other more common conditions, which can be frustrating and distressing for patients. This may also lead to delays in receiving treatment. When patients are diagnosed with TED, they are currently faced with limited treatment options targeting ‘generalised inflammation’. These treatments do not specifically target the underlying cause and drivers of TED,” said Dr Jimmy Uddin, Consultant Ophthalmologist, Oculoplastic & Orbital Surgeon, Moorfields Eye Hospital and St George’s Hospital Medical School, London “Teprotumumab offers eligible TED patients in the UK an important new treatment option.”

The OPTIC clinical trial was a prospective, multi-centre randomised, double-blind, placebo-controlled, Phase III trial of the IGF-1R inhibitor teprotumumab or placebo in adults with Graves’ disease and active moderate-to-severe thyroid eye disease. (NCT03298867)

83 patients between the ages of 18-80 were recruited and randomised 1:1 to receive 8 intravenous infusions of either teprotumumab or placebo. Infusions were administered every 3 weeks over 21 weeks, with a final clinical evaluation at week 24. The initial dose of teprotumumab was 10mg/kg, with each subsequent infusion dosed at 20mg/kg.

The primary endpoint of the trial was proptosis response, defined as a reduction of at least 2mm in proptosis from baseline in the study eye without a corresponding increase of at least 2mm in the fellow (contra-lateral) eye at week 24.

See citation- Douglas RS et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020, 382:341