How Does Tepezza Cause Hearing Loss?

The short version: the receptor Tepezza was designed to block is the same receptor the inner ear depends on to keep its sensory cells alive. Blocking it systemically, every three weeks, for five months, can damage structures that do not grow back.

What Tepezza Is and What It Does

Tepezza (teprotumumab-trbw) is a monoclonal antibody approved by the FDA in January 2020 — the first and only drug approved to treat thyroid eye disease.

Thyroid eye disease is an autoimmune condition, most often associated with Graves' disease, in which the immune system attacks tissue in the orbit. The muscle and fat behind the eye swell, pushing the eye forward. Patients develop proptosis (bulging), double vision, eye pain, light sensitivity, and in severe cases vision-threatening complications. The active inflammatory phase typically lasts six months to two years.

Tepezza works by binding to and blocking the insulin-like growth factor-1 receptor (IGF-1R). In TED, IGF-1R is over-expressed on orbital fibroblasts and appears to sit at the center of the inflammatory cascade driving tissue expansion. Blocking it interrupts that process — and it works: in the pivotal trials, 82% of Tepezza patients showed meaningful reduction in eye bulging versus 10% on placebo.

The problem is that IGF-1R is not confined to the orbit.

Why That Receptor Matters to the Inner Ear

IGF-1 signaling is essential to the development, survival, and repair of the cochlea — the spiral structure in the inner ear that converts sound waves into nerve signals. The cochlea's sensory hair cells depend on that signaling pathway to stay viable and to recover from stress.

This relationship was documented in the medical literature well before Tepezza existed. Research going back years established that IGF-1 deficiency is associated with sensorineural hearing loss, and that IGF-1 plays a protective role in cochlear tissue.

Tepezza is not delivered to the eye. It is infused intravenously and circulates throughout the body, blocking IGF-1R wherever it is expressed — including in the inner ear. The drug is given at 10 mg/kg for the first dose and 20 mg/kg for seven more, once every three weeks.

The result is repeated, sustained systemic blockade of a receptor the cochlea needs.

Cochlear hair cells in humans do not regenerate. Damage to them is permanent. That single biological fact is why "reversible side effect" and "sensorineural hearing loss" are difficult claims to hold at the same time — and it is why the permanence question sits at the center of this litigation.

Researchers publishing case reports in 2021 in Ophthalmic Plastic and Reconstructive Surgery proposed exactly this mechanism: that the hearing damage they were observing resulted from inhibition of the IGF-1 and IGF-1R pathway.

Notably, Tepezza's own prescribing information acknowledges that formal studies of the drug's molecular, biochemical, and physiologic effects were not conducted.

What the Research Actually Found

The pre-approval trials: 10%, described as reversible

Tepezza's safety profile was established in two randomized, placebo-controlled trials — Study 1 (NCT01868997) and Study 2, the OPTIC trial (NCT03298867) — involving 170 patients total, of whom 84 actually received Tepezza. Horizon reported hearing-related adverse events in roughly 10% of treated patients, including deafness, eustachian tube dysfunction, hyperacusis, hypoacusis, and autophony, and characterized them as generally temporary and resolving after treatment ended.

Eighty-four patients is a small evidentiary base on which to characterize the permanence of an injury.

May 2021 — Stanford / ENDO 2021: 65%

Researchers presented findings at the Endocrine Society's ENDO 2021 conference evaluating patients who received at least four Tepezza infusions. Of 26 patients studied, 17 (65%) developed otologic symptoms. Broken down: six (23%) reported hearing loss, seven (27%) developed tinnitus, three (12%) reported ear-plugging sensation, and roughly 29% developed autophony. Symptoms emerged after an average of about 3.6 infusions. Some patients showed new or worsening sensorineural hearing loss — the type caused by damage to inner ear hair cells.

The researchers recommended that physicians warn patients about potential hearing effects and that patients receive baseline audiogram testing before treatment.

That recommendation would not appear on Tepezza's label for another two years. Source: Endocrine Society, ENDO 2021 — "Increased Risk of Hearing Impairment With New Thyroid Eye Disease Treatment"

August 2021 — Irreversible sensorineural hearing loss documented

A case report in The Annals of Otology, Rhinology, and Laryngology described a 61-year-old woman with Graves' disease who developed bilateral hearing loss, sound distortion, and tinnitus after Tepezza treatment. Infusions were stopped and she was treated with oral corticosteroids. Four months later her hearing had not improved. The authors described it as one of the first documented cases of ototoxicity producing irreversible sensorineural hearing loss in the setting of teprotumumab treatment. PubMed: 34448414

2021–2022 — Case series proposes the mechanism

A case series published in Ophthalmic Plastic and Reconstructive Surgery evaluated four patients with significant Tepezza-associated hearing loss, drawn from a treated population of 28. The authors warned that the drug may cause a range of irreversible hearing symptoms varying from mild to severe, attributed the effect to IGF-1/IGF-1R pathway inhibition, and cautioned that the incomplete understanding of Tepezza's auditory effects should factor into prescribing decisions. PubMed: 34085994

February 2022 — The permanence data

A study in the American Journal of Ophthalmology followed patients out to eight months after their last infusion. Among those who had developed subjective hearing loss or decreased word comprehension, only 45.5% had fully recovered. Roughly 20% still had autophony and nearly 10% still had ear-plugging symptoms at that follow-up point. PubMed: 35227694

That finding is difficult to reconcile with a warning label describing these effects as temporary.

2023 — Dose-response evidence

A Stanford case study reported a 64-year-old woman who developed significant bilateral hearing loss during a full-dose Tepezza course in 2021. Her symptoms resolved after treatment stopped. A year later she was re-treated at a substantially lower dose and did not experience the same hearing effects — evidence of a dose-dependent relationship, which is one of the classic indicators of genuine causation rather than coincidence.

Adverse event reports

By the end of 2021, the FDA had received reports of at least 135 patients experiencing hearing complications after Tepezza, including tinnitus, hypoacusis, and deafness.

July 2023: The Label Finally Changes

On July 17, 2023, the FDA approved an updated Tepezza label adding to the Warnings and Precautions section that the drug may cause severe hearing impairment including hearing loss, which in some cases may be permanent, and instructing prescribers to assess patients' hearing before, during, and after treatment and to weigh the risk-benefit balance with patients.

Approval: January 2020. Warning: July 2023. Three and a half years.

What Plaintiffs Allege Horizon Knew

The failure-to-warn claims in MDL 3079 rest on the gap between what the label said and what Horizon allegedly had in hand.

Study 401. Court filings allege that Horizon's internal expanded access program, Study 401, showed hearing-related adverse events in up to 40% of patients — four times the labeled rate — and that these results were known as early as March 2020, roughly two months after launch.

The whistleblower. Plaintiffs allege that Dr. Wenzhong "Jerry" Liu, a Horizon physician with a background in clinical development and medical affairs, challenged the accuracy of the 10% figure internally, pointing to the Study 401 data, and pressed for disclosure to regulators, physicians, and the public. He was terminated, and subsequently filed a wrongful termination lawsuit against the company.

The CBE pathway. Federal regulation gives a branded drug manufacturer a specific tool for this exact situation: the "changes being effected" supplement, which permits strengthening a warning immediately, without waiting for FDA approval, when newly acquired safety information emerges. This is the mechanism at the heart of the Supreme Court's decision in Wyeth v. Levine, 555 U.S. 555 (2009), which is why preemption defenses generally fail in branded pharmaceutical failure-to-warn cases. Plaintiffs allege Horizon did not use it, and instead took a slower regulatory route while sales continued — $3.2 billion in 2021 alone.

FDA signal detection. The FDA's adverse event reporting system flagged Tepezza hearing impairment as a formal safety signal in early 2023.

These are allegations made in pending litigation. They have not been proven and Horizon and Amgen dispute them.

Symptoms to Watch For

If you received Tepezza infusions, these are the changes worth documenting and discussing with an audiologist:

• Difficulty following conversation, particularly in restaurants or other noisy settings
• Ringing, buzzing, roaring, or humming in one or both ears
• A persistent plugged, full, or pressurized sensation
• Your own voice sounding unusually loud, echoing, or hollow (autophony)
• Sounds seeming muffled, distant, or distorted
• Clicking or popping sounds
• New sensitivity to ordinary sound levels
• Dizziness or balance changes
• Ear pain resembling an infection with no infection present

If you are currently receiving Tepezza and notice hearing changes, talk to your doctor. Your health decisions should be made with your physician, not around a potential legal claim.

Get Your Case Reviewed

If you received Tepezza and developed hearing loss or tinnitus, we can review your records at no cost and tell you whether you have a claim.

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Sources

1. Endocrine Society, ENDO 2021 — Increased Risk of Hearing Impairment With New Thyroid Eye Disease Treatment
2. The Annals of Otology, Rhinology, and Laryngology (2021) — PubMed 34448414
3. Ophthalmic Plastic and Reconstructive Surgery (2021) — PubMed 34085994
4. American Journal of Ophthalmology (2022) — PubMed 35227694
5. TEPEZZA Prescribing Information, FDA — accessdata.fda.gov
6. FDA Drug Trial Snapshot: Tepezza — fda.gov
7. Wyeth v. Levine, 555 U.S. 555 (2009)

ATTORNEY ADVERTISING. This page is informational and is not medical or legal advice. Allegations described are from pending litigation and have not been proven.