Regulatory Decision Summary for Tepezza

This New Drug Submission (NDS) was filed to obtain market authorization for Tepezza (teprotumumab for injection) in adults for the treatment of moderate to severe Thyroid Eye Disease (TED).

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Thyroid Eye Disease (TED) is a rare, serious, debilitating and painful autoimmune disease associated with major comorbidities that can lead to visual disability. There are currently no authorized medical treatments in Canada for patients with active or inactive TED.

Benefit

Active TED

Two phase 3 studies in patients with active TED showed a statistically significant and clinically meaningful benefit of teprotumumab over placebo based on the results of the primary endpoint which is the proptosis responder rate at Week 24. Findings on the secondary endpoints supported the primary efficacy findings.

Inactive TED

The submission included a single study assessing the efficacy and safety of Tepezza in patients with inactive TED. Important limitations were identified in this study and therefore, the evidence provided to support the use of Tepezza for the treatment of inactive TED is not deemed sufficient at this time to conclude on a favourable benefit-risk profile, considering the safety profile of this drug as described below. Tepezza is not recommended for the treatment of inactive TED and therefore, the indication has been restricted to patients with active TED only.

Risk

The identified frequent but usually non serious adverse events associated with teprotumumab include infusion reactions, muscle spasms, dry skin, alopecia, nail disorders, diarrhea, nausea, dysgeusia, weight loss, urinary tract infections and menstrual disorders. Tepezza is also associated with some serious adverse events: hyperglycemia-related events (including diabetic ketoacidosis), hearing impairment (e.g. hearing loss), and exacerbation of inflammatory bowel disease. The long-term impact of these events on a person’s quality of life and general health has not yet been characterized. No deaths were reported during the TED clinical program. These risks have been properly mitigated through labelling and will be closely monitored through pharmacovigilance activities. Tepezza was also identified as a teratogen and is contraindicated during pregnancy. It was also shown to cause general growth retardation in fetuses and juvenile animals. These effects have been labelled in the product monograph.

An updated Risk Management Plan (RMP) for Tepezza was reviewed by Health Canada and considered acceptable.

Recommended Dose and Dosage Adjustment was an intravenous infusion of 10 mg/kg for the initial dose followed by an intravenous infusion of 20 mg/kg every three weeks for 7 additional infusions, which was supported by phase 3 and phase 2 active TED studies.

The chemistry and manufacturing information submitted for Tepezza has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Benefit/Risk

Overall, the benefit-risk profile was favourable for Tepezza (teprotumumab for injection) for the approved indication, i.e., Tepezza (teprotumumab for injection) in adults for the treatment of moderate to severe active Thyroid Eye Disease (TED), when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Tepezza, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.