Teprotumumab-TRBW

CAMBRIDGE, England--(BUSINESS WIRE)--Today, Amgen announced that the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for TEPEZZA® (teprotumumab) as the first therapy specifically licensed for the treatment of adult patients with moderate-to-severe Thyroid Eye Disease (TED). Affecting approximately 50,000 people in the UK,1 TED is a progressive and potentially vision-threatening condition, which can cause eye bulging, double vision, eye pain, redness and swelling.2 People living with TED often experience anxiety and depression, concerns about their facial appearance and a loss of confidence.3 This can impact their ability to work, socialise and maintain relationships.3,6 “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.” Teprotumumab’s marketing authorisation in the UK is supported by multiple clinical studies,5,7,8,9 including the Phase 3 clinical trial, OPTIC (n=83).5 Other clinical studies that supported the marketing authorisation in the UK include the TED01RV Phase 2 clinical study (n=88),7 the HZNP-TEP-403 Phase 4 clinical study (n=62),8 and the OPTIC-J Phase 3 study in Japan (n=54).9 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]).5 “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. “Teprotumumab offers eligible TED patients in the UK an important new treatment option.” The safety data for teprotumumab is based on multiple clinical studies.5,7,8,9 The most common side effects observed in 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%).4 Amgen will work with the National Institute for Health and Care Excellence (NICE) to seek reimbursement of teprotumumab for all eligible patients. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Notes to Editors About Thyroid Eye Disease (TED) TED is a serious, progressive and potentially vision-threatening autoimmune disease.10 It often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signalling complex on cells within the retro-orbital space.11,12 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness.13,14 Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and double vision.2 About teprotumumab Teprotumumab is a monoclonal antibody that specifically targets and blocks the insulin-like growth factor-1 receptor (IGF-1R), which is thought to play a central role in the development of TED.15 It binds to the IGF-1R, preventing it from being activated and sending signals that lead to muscle and tissue expansion, as well as inflammation behind the eye.15 This can help reduce TED symptoms, such as proptosis (eye bulging).4,5 For further product information, please see the Summary of Product Characteristics, which will be available at: https://www.medicines.org.uk/emc About the Phase 3 OPTIC clinical trial A prospective, multi-centre randomised, double-blind, placebo-controlled, Phase 3 trial of the IGF-1R inhibitor teprotumumab or placebo in adults with Graves’ disease and active moderate-to-severe thyroid eye disease.5 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.5 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 24.5 For more information on the OPTIC clinical trial go to: https://clinicaltrials.gov/study/NCT03298867. About Amgen UK Amgen’s mission is to serve patients. A biotechnology innovator since 1980, our science- based heritage is at the heart of everything we do. We remain on the cutting edge of innovation, using technology and human genetic data to push beyond what is known today. In the UK, Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. As a regional hub, we employ around 650 people in the UK and Ireland across our commercial, R&D and corporate functions. Committed to driving sustainable solutions that can adapt to an ever-evolving health system, we are proud to serve patients every day. For more information visit: https://www.amgen.co.uk/ References 1 British Thyroid Foundation. Thyroid eye disease. Available at: https://www.btf-thyroid.org/thyroid-eye-disease/1000. Last accessed: May 2025. 2 Royal National Institute of the Blind (RNIB). Thyroid eye disease. Available at: https://www.rnib.org.uk/your-eyes/eye-conditions-az/thyroid-eye-disease/#:~:text=It%20is%20well%20known%20that,be%20taking%2C%20such%20as%20steroids. Last accessed: May 2025. 3 Smith TJ, et al. How patients experience thyroid eye disease. Front. Endocrinol. 2023;9(14):1283374. 4 TEPEZZA (teprotumumab) Summary of Product Characteristics. Will be available at: https://www.medicines.org.uk/emc 5 Douglas RS, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med 2020;382:341-352. 6 British Thyroid Foundation. Thyroid eye disease: patient leaflet. Available at: https://www.btf-thyroid.org/thyroid-eye-disease-leaflet#:~:text=You%20may%20also%20feel%20anger,both%20social%20and%20at%20work. Last accessed: May 2025. 7 Smith TJ, et al. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med 2017;376:1748-1761. 8 Douglas RS, et al. Efficacy and Safety of Teprotumumab in Patients with Thyroid Eye Disease of Long Duration and Low Disease Activity. JCEM 2024;109(1):25-235. 9 Hiromatsu Y, et al. A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patients. Lancet Reg Health West Pac. 2025;55:101464. 10 Ponto KA, et al. Quality of life and occupational disability in endocrine orbitopathy. Dtsch Arztebl Int. 2009;106(17):283-289. 11 Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257. 12 Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol. 2003;170:6348-6354. 13 McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO ) survey. Br J Ophthalmol. 2007;91:455-458. 14 Bartalena L, et al. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy. Eur J Endocrinol. 2021;185(4):G43-G67. 15 Patel A, et al. A New Era in the Treatment of Thyroid Eye Disease. Am J Ophthalmol. 2019;208:281-288.

In the first quarter, sales of the top three products Amgen gained from its $27.8 billion acquisition of Horizon Therapeutics fell far short of analyst expectations, with each seeing a double-digit sequential sales decline. It’s been 19 months since Amgen completed its $27.8 billion acquisition of Horizon Therapeutics, and the California company is still struggling to build momentum for three of the prized possessions of the deal—rare disease drugs Uplizna, Krystexxa and Tepezza.When Amgen presented its first-quarter earnings Thursday, none of the trio met analyst expectations. With sales of $91 million, Uplizna came up $20 million short of the consensus projection. Meanwhile, Krystexxa’s haul of $236 million was $57 million shy of expectations, and Tepezza’s $381 million figure was $69 million off the mark.The shortfall for the Horizon products came during a quarter in which most of the company’s other treatments exceeded expectations. In fact, Amgen’s overall revenue of $8.1 billion was a 9% increase year over year and topped the analyst consensus. The lack of success for the Horizon drugs is apparently becoming a sore subject for Amgen execs. During a conference call, after an analyst asked about the stagnant sales of Tepezza and referred to a “couple years” since the Horizon buyout, Chief Financial Officer Peter Griffith was quick to make a correction.“Just a reminder that the transaction closed in October of 2023,” Griffith said. “It’s been about a year and a half, although so much has happened in the world it might feel like more than that.”The most vexing Horizon product has been with Tepezza, which remains the lone drug on the market for thyroid eye disease. In its second full year on the market under Horizon, in 2022, it generated $1.96 billion in revenue. But, in the following year, sales came in at $1.77 billion, followed by $1.85 billion last year, when there were signs that Tepezza was rallying.But the $381 million quarterly result for the treatment was a stunner—it’s lowest figure for a three-month period since the first quarter of 2021 and a 17% sequential decline.“Sales of Tepezza and Krystexxa were adversely impacted in the quarter by changes to U.S. wholesaler inventory levels," Amgen’s chief commercial officer Murdo Gordon explained. "We do not expect similar deductions in inventory levels for the remainder of the year."But the result sounded an alarm bell with Mizuho Securities analyst Salim Syed, who noted the 9% decline in volume and 8% decrease in inventory levels, which “likely put the Horizon acquisition into even more question,” he wrote in a note to investors.Gordon explained that the initial uptake of Tepezza was strong as it was a long-awaited answer for people who had serious cases of the eye disease and were readily prescribed the treatment from plastic surgeons. To grow sales, Tepezza needs to secure more prescriptions from general ophthalmologist and endocrinologists, he added.But tapping this segment of the market “may be more challenging to penetrate than previously communicated by the company,” analysts from Citi wrote in a note to clients.Amgen is far from abandoning hope for Tepezza. The company recently gained a thumbs-up from Europe’s Committee for Medicinal Products for Human Use nd is ready to launch there upon an expected approval. An additional edge Amgen could secure to help spur sales would be to earn approval for a subcutaneous version of Tepezza, as opposed to the 60- to 90-minute infusions patients undergo every three weeks as it stands. A subQ option would allow patients to receive the treatment faster and in many more settings than at infusion centers. Testing on the formulation began last year.On a much smaller scale, sales also were disappointing for Uplizna, which fell sequentially from $101 million in the fourth quarter to $91 million in the first.But help has already arrived in the form of a label expansion last month, making Uplizna the first drug to win an FDA approval for immunoglobulin G4-related disease (IgG4-RD), a disease that affects 20,000 patients in the U.S. and has no standard of care. Additionally, Amgen announced Thursday that it has secured an FDA decision date of Dec. 14 for Uplizna to treat patients with generalized myasthenia gravis (gMG).With respect to all of the Horizon products, Amgen’s message on Thursday was to give them more time.“It’s a very young portfolio of products where we’re really just beginning to address the severe diseases that these drugs treat,” Jay Bradner, Amgen’s R&D chief, said. “Whether it’s Tepezza, Uplizna, Krystexxa or Tavneos, these are going to be key growth-driving products for us over the long haul.”