Background Analysis: US FDA Advisory Committee to Horizon Therapeutics’ Teprotumumab, Proposed to Treat Thyroid Eye Disease – DEC 13, 2019 (DOAC)

Announcement

The US FDA has scheduled a Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) meeting for Friday, December 13, 2019. The committee will discuss and make recommendations on a biologics license application (BLA) for teprotumumab solution for intravenous use, submitted by Horizon Pharma Ireland, Ltd. (Horizon), proposed for the treatment of active thyroid eye disease. Teprotumumab is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor 1 receptor (IGF-1R).

Clinical Trials of Proposed Indication

A summary of the design and top-line results of the pivotal, phase 3 clinical trial, named OPTIC (Treatment of Graves’ Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study), is provided below, based on a press release made by Horizon on February 28, 2019. Comprehensive data and detailed analyses by both Horizon and the FDA will be made available two days prior to the DODAC meeting, in meeting materials posted by the FDA. These materials will be summarized on the day they are posted, in our subsequent report, the Briefing Summary. At the time of publishing this report, trial results were not posted to ClinicalTrials.Gov (ClinicalTrials.Gov ID: NCT03298867).

Pivotal Trial Design

OPTIC was designed to investigate the efficacy, tolerability and safety of teprotumumab in patients with active thyroid eye disease (TED). Eighty-three patients were assigned to receive teprotumumab or placebo in eight intravenous infusions (10mg/kg for their first infusion followed by 20mg/kg for the remaining seven infusions) every three weeks for 21 weeks.

The primary endpoint was a responder rate of ≥ 2 mm reduction of proptosis in the study eye (without deterioration in the fellow eye) at Week 24.

Top-Line Results

In the intent-to-treat population, 34/41 (82.9%) patients receiving teprotumumab and 4/42 (9.5%) patients receiving placebo were proptosis responders at Week 24 (p˂0.001).

All secondary endpoints were also met (p≤0.001), which include the effect of teprotumumab vs. placebo on:

·       Overall responder rate at Week 24 (primary endpoint in the Phase 2 study): Percent of participants with ≥2 point reduction in Clinical Activity Score (CAS) and ≥2 mm reduction in proptosis from baseline, provided there is no corresponding deterioration (≥2-point/mm increase) in CAS or proptosis in the fellow eye.

·       Percent of participants with a CAS value of 0 or 1 at Week 24 in the study eye.

·       Percent of patients with a change from baseline of at least one grade in diplopia (double vision).

·       Mean change in proptosis measurement from baseline to Week 24 in the study eye.

·       Mean change in Graves’ Ophthalmopathy Quality of Life from baseline to Week 24.

The safety profile of teprotumumab in OPTIC was similar to that seen in the Phase 2 study (ClinicalTrials.Gov ID: NCT01868997) with no new safety observations. The drop-out rate was low (<5%) and balanced across placebo and treatment arms. There were no deaths during the study and a total of three serious adverse events: in the placebo arm, one patient had a visual field defect and received orbital decompression surgery and discontinued study; in the teprotumumab arm, one patient had pneumothorax (considered not related to study drug) and another had an infusion reaction that led to discontinuation of study drug. The vast majority of treatment-emergent adverse events were mild to moderate in intensity and no other adverse events resulted in discontinuation.

Regulatory Background

US Regulatory Background

March 8, 2020– PDUFA goal date

July 2019 - BLA filing date (BLA 761143)

Breakthrough Therapy, Orphan Drug and Fast Track designations

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: Horizon Pharma Ireland, Ltd. Drug Name: teprotumumab solution for intravenous use Drug Class: inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) Indication: active thyroid eye disease

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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.