American doctors have documented 84 hearing-related adverse events in patients taking teprotumumab (Tepezza) for thyroid eye disease, a treatment which is being evaluated by the TGA for use in Australia.
They found use of teprotumumab in patients with thyroid conditions was associated with a nearly 24-fold increased likelihood of any hearing disorder.
They said the association was specifically elevated for a variety of deafness conditions – e.g. bilateral deafness, Eustachian tube disorders, hypoacusis and tinnitus.
Teprotumumab is approved by the FDA to treat thyroid eye disease, also known as Graves’ disease, which is a painful and potentially sight-threatening disease.
Its manufacturer, Amgen, said Tepezza “may cause severe hearing impairment including hearing loss, which in some cases may be permanent.”
The University of Alabama researchers said accumulating case reports and series had suggested that teprotumumab may significantly increase the risk of hearing impairment that, in some cases, does not resolve.
They suggested patients undergoing the therapy should receive warnings about the increased risk of hearing-related impairments and receive audiometry before, during, and after treatment.
The doctors investigated the association between hearing impairment and teprotumumab use by analysing the United States Food and Drug Administration Adverse Event Reporting System, a publicly accessible database used for postmarketing surveillance and research.
They selected all adverse event reports containing teprotumumab or Tepezza and a similar comparison group from all patients with the same indications for teprotumumab use (e.g. autoimmune thyroiditis, endocrine ophthalmopathy, and hyperthyroidism) but who had not received the drug.
Hearing impairment events were identified using the hearing impairment Standardized MedDRA Query.
They identified 940 teprotumumab-associated adverse events, including 84 hearing-related adverse events, since April 2020.
A comparison group of 32,794 nonteprotumumab adverse events was identified with 127 hearing-related adverse events reported.
The study was reported in Ophthalmic Plastic and Reconstructive Surgery November/December 2024.
TGA application in Australia
Amgen said the infusion was a fully human monoclonal antibody and targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) and was approved in the US, Brazil and Saudi Arabia to treat thyroid eye disease.
Amgen said in a media release in April 2024 it had submitted a marketing authorisation application to the Therapeutic Goods Administration (TGA) in Australia for teprotumumab, the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain, and a New Drug Submission (NDS) to Health Canada.
On 13 January 2025 an Advisory Committee on Medicines statement from its December 2024 meeting, posted on the TGA website, showed that an application by Amgen Australia for Tepezza as a new medicine for thryoid eye disease was under evaluation by the TGA. It was designated a priority.
In the April 2024 media release, Amgen said the treatment “may cause severe hearing impairment including hearing loss, which in some cases may be permanent.”
“Assess patients’ hearing before, during, and after treatment with Tepezza and consider the benefit-risk of treatment with patients,” Amgen advised.
The most common adverse reactions (incidence ≥5% and greater than placebo) were muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders, it said.
The American researchers were Dr Gerald McGwin from the Department of Epidemiology, School of Public Health and the Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama, Dr Chynthia Owsley from the Department of Ophthalmology and Visual Sciences, and Dr Matthew Vicinanzo from the Department of Epidemiology and Alabama Ophthalmology Associates.
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