11.16.20

Horizon: New Data Build on Growing Evidence Supporting Tepezza Efficacy in Thyroid Eye Disease (TED)

Source: Horizon Therapeutics

Horizon Therapeutics announced new Tepezza (teprotumumab-trbw) data presented at the American Academy of Ophthalmology Annual Meeting (AAO 2020 Virtual), including findings suggesting benefits of Tepezza in the less severe eye of patients with Thyroid Eye Disease (TED), and new data from the OPTIC 48-week follow-up study and OPTIC-X clinical trial.

Tepezza is the first and only medicine approved by the FDA for the treatment of TED–a serious, progressive and vision-threatening rare autoimmune disease.1

“We continue to analyze our existing clinical trials and pursue new research to fully understand the impact Tepezza has on this challenging disease,” Elizabeth H.Z. Thompson, PhD, group vice president, development and external search, Horizon, said in a company news release. “Our data demonstrating the effect of Tepezza at varying stages of the disease, including in the less severely affected eye and in patients who have had Thyroid Eye Disease for a longer period of time, will help advance the science of Thyroid Eye Disease and instill greater understanding of the role Tepezza can play in improving patient outcomes.”

Compelling Response in Less Severe TED

Improvement in Fellow Eye of Patients with TED: Pooled Analyses from Teprotumumab Studies (PO305)

In patients with TED, one eye can have more severe symptoms than the other. The Tepezza phase 2 clinical trial and OPTIC phase 3 confirmatory clinical trial designated the more severely affected eye as the “study eye”.2,3 This new analysis focused specifically on efficacy of Tepezza in treating the less severe eye, or “fellow eye”, of patients in the Tepezza phase 2 and 3 trials. Researchers analyzed the intent-to-treat (ITT) population in the phase 2 and phase 3 studies, defined as all patients randomized to receive Tepezza (n=84) and all patients randomized to receive placebo (n=87). The fellow eye was less proptotic than the study eye in both the Tepezza (21.61 mm vs. 23.02 mm) and placebo (21.97 mm vs. 23.15 mm) groups, indicating less severe disease. Additionally, the fellow eye, on average, demonstrated less inflammation based on the clinical activity score (CAS) than the study eye in both the Tepezza (CAS: 4.3 vs. 5.1 points) and placebo (CAS: 4.7 vs. 5.3 points) groups.

Findings suggest that Tepezza may offer benefits in patients with less severe TED:

  • At Week 24, more Tepezza patients were proptosis (eye bulging) responders (≥2 mm reduction) in the fellow eye than placebo patients (63.1 percent vs. 8.0 percent, p<0.001), with a mean reduction in proptosis of 2.39 mm for Tepezza patients and a mean increase in proptosis of 0.15 mm for placebo patients (p<0.001).
  • 30 patients (34.5 percent) in the placebo group had a worsening of proptosis at Week 24 in the fellow eye compared to 0 patients (0 percent) in the Tepezza group.
  • CAS in the fellow eye decreased from baseline by a mean of -3.42 points in the Tepezza group compared to -2.00 points in the placebo group (p<0.001) at Week 24.
  • More Tepezza patients (63.1 percent) than placebo patients (26.4 percent) had a CAS of 0 or 1 – signifying disease inactivation – in the fellow eye at Week 24 (p<0.001).

“We know from the clinical development program that Tepezza significantly reduces proptosis and Thyroid Eye Disease-related inflammation in patients with moderate-to-severe disease, and now with this new analysis of the phase 2 and 3 data, we have evidence pointing to efficacy in patients with less severe disease as well,” Raymond Douglas, MD, PhD, study author and director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center, said in the news release. “We believe this robust effect is the result of the mechanism of Tepezza that effectively targets the underlying molecular pathways that cause Thyroid Eye Disease.”

Additional Findings from the OPTIC 48-Week Follow-Up Study and OPTIC-X Clinical Trial

Long Term Assessment of Proptosis and Diplopia from the OPTIC Trial of Teprotumumab in Thyroid Eye Disease (PA038)

Additional data from the OPTIC phase 3 confirmatory clinical trial and the OPTIC-X open-label extension clinical trial were also included in an abstract and presented during AAO, supplementing the topline results on proptosis response announced in July 2020. The OPTIC trial included a 24-week treatment period (treatment every three weeks for a total of eight infusions) and a 48-week off-treatment follow-up period. OPTIC-X evaluated Tepezza in patients who were enrolled in OPTIC and were either proptosis non-responders at Week 24 or were proptosis responders at Week 24 but flared during the 48-week off-treatment follow-up period.

New OPTIC 48-week off-treatment follow-up study findings include the following:

  • The majority of Tepezza patients who had at least 1 grade of diplopia (double vision) improvement at Week 24 in OPTIC maintained their response at Week 72 (11/19; 58 percent) without receiving additional TED treatment.
  • 50 percent of Tepezza patients (8/16) who had a diplopia score of 0 at Week 24 in OPTIC maintained a diplopia score of 0 at Week 72 without receiving additional TED treatment.

New OPTIC-X findings include the following:

  • 61 percent of patients (14/23) who received placebo during the OPTIC trial and then entered OPTIC-X and received Tepezza were considered diplopia responders (≥1 grade improvement) at Week 24. This is consistent with results from the OPTIC trial, where 68 percent of patients (19/28) who received Tepezza had a change from baseline of at least 1 grade in diplopia at Week 24. OPTIC-X patients had an average of 12 months of TED compared with six months in OPTIC.
  • Five patients who received placebo during the OPTIC trial and then entered OPTIC-X had a CAS of 0 or 1, which means they had minimal or no inflammation. Of those, 60 percent (3/5) were proptosis responders at Week 24 (≥2 mm improvement in proptosis from baseline in the study eye without deterioration in the fellow eye at Week 24).

There were no new safety concerns in OPTIC-X or the OPTIC 48-week off-treatment follow-up period, including in patients who received additional Tepezza treatment.

References

  1. Barrio-Barrio J, et al. Graves’ Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:1-16.
  2. Smith, et al. Teprotumumab for Thyroid-Associated Ophthalmology. N Engl J Med. 2017;376:1748-1761.
  3. Douglas, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020;382(4):341-352.
  4. Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
  5. 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.
  6. Ross DS, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J. 2016;5(1):9-26.
  7. 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.

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