Recently, a company announced positive top-line data from two clinical trials, which provides more and more evidence to support the efficacy and safety of Tepezza (teprotumumab-trbw) in the treatment of thyroid ophthalmopathy (TED).
Tepezza is the first and only drug approved by the US FDA to treat TED. TED is a serious, progressive, and rare autoimmune disease that threatens vision. It is associated with exophthalmos (eyeball), double vision, blurred vision, pain, inflammation, and facial defects.
Tepezza is a fully human monoclonal antibody and insulin-like growth factor-1 receptor (IGF-1R) targeted preparation, which was approved by the US FDA on January 21, 2020. Previously, the FDA has granted teprotumumab the orphan drug designation, fast track designation, breakthrough drug designation, and priority review qualification for the treatment of active TED.
The OPTIC Phase 3 confirmatory clinical trial and the OPTIC-X open label extension clinical trial are part of Horizon's development project, which is evaluating the safety and effectiveness of Tepezza in the treatment of TED patients. The OPTIC Phase 3 confirmatory clinical trial includes a 24-week treatment period and a 48-week follow-up period of discontinuation. In the study: the 24-week treatment period evaluated Tepezza or placebo injections every 3 weeks for a total of 8 injections. The primary endpoint is the first The exophthalmos (eyeball swelling) of the 24-week experimental eye was reduced by ≥2 mm from the baseline (the contralateral eye did not deteriorate). At week 24, patients with exophthalmos responded to the 48-week withdrawal follow-up period and did not receive additional TED treatment, including Tepezza.
The OPTIC-X trial evaluated the safety and effectiveness of Tepezza in TED patients enrolled in the OPTIC trial. These patients were either non-responders at the 24th week of treatment, or patients who had exophthalmic responses at the 24th week. The condition relapsed during the 48-week follow-up period of drug withdrawal. Non-responders were defined as an improvement of less than 2 mm from baseline in exophthalmos at week 24. Recurrence was defined as: during the 48-week follow-up period after the end of treatment, at least the 24th week of the exophthalmos was lost and the improvement of 2 mm (even if the exophthalmos was still better than the baseline examination) or the number of signs of inflammation or symptoms increased significantly and the exophthalmos Patients who do not get worse. During the 48-week follow-up period of discontinuation of the OPTIC trial, patients may relapse at any point in time.
The top-line results are as follows: (1) Among the patients who received placebo in the OPTIC trial and then received Tepezza in the OPTIC-X trial, 89% (33/37) of the patients achieved reduction of exophthalmos in the 24th week of treatment Primary endpoint ≥2 mm (average reduction of 3.5 mm). This is consistent with the results of the OPTIC trial: at the 24th week of treatment, 83% of patients treated with Tepezza (n=41) had a reduction of ≥2 mm in exophthalmos (average reduction of 3.3 mm). The OPTIC-X trial's other endpoint results, including diplopia and clinical activity score (CAS) results are similar to those observed in the OPTIC trial.
Patients who received placebo in the OPTIC trial and the first course of Tepezza in the OPTIC-X trial had an average TED diagnosis time of 1 year and a maximum of 16 months. In the OPTIC trial, the average TED diagnosis time For 6 months.
During the 48-week follow-up period of the OPTIC trial, most of the Tepezza-treated patients who responded with exophthalmos at week 24 of the OPTIC trial maintained their exophthalmos response at week 72 (19/34; 56%) and did not receive Additional TED treatment. Of the 15 patients who were assessed as not maintaining a exophthalmos response, 8 patients were at least 2 mm better than baseline at the last evaluation of the OPTIC trial's 48-week discontinuation follow-up period. Among these 15 patients, 4 patients who discontinued the study prematurely, 2 patients whose condition deteriorated slightly but not enough to meet the OPTIC-X recurrence criteria, and 9 patients met the OPTIC-X recurrence criteria before the 72nd week at the end of the treatment period (among them 8 cases entered OPTIC-X for retreatment, 1 case did not enter OPTIC-X).
During the 48-week discontinuation follow-up period of OPTIC, from week 24 to week 72, the durability of other endpoints was similar, including diplopia and CAS. Among the relapsed patients who received an additional course of Tepezza retreatment, more than 60% of the patients had an improvement of ≥2 mm from the OPTIC-X baseline at the 24th week. In the OPTIC trial, only 5 patients did not achieve exophthalmos response after completing the entire course of Tepezza treatment. Among them, 2 patients received an additional course of Tepezza treatment in the OPTIC-X trial or the improvement of exophthalmos was ≥2 mm.
During the 48-week discontinuation follow-up period of OPTIC-X or OPTIC, no new safety issues were found, including in patients receiving additional Tepezza treatment.
The detailed data of the above two trials will be announced at a future medical conference. Professionals say: "The data from the OPTIC-X trial provides evidence that Tepezza has the potential to effectively reduce the exophthalmos of TED patients, and the duration of TED disease in these patients is longer than that of the initial study in Phase 2 and Phase 3 clinical trials. Long. In addition, the data also shows that some patients may benefit from additional courses of Tepezza treatment, and the data shows that these patients can experience treatment improvement without increasing safety issues. We are further understanding the early efficacy of the Tepezza project and the patient’s treatment of Tepezza The safety of treatment."
Experts said: "The results of patients who received Tepezza in the OPTIC trial are similar to those of patients who transitioned from receiving a placebo in the OPTIC trial to receiving Tepezza in the OPTIC-X trial. The results are similar and effective. Previously, they were diagnosed as TED. Of patients do not have FDA-approved treatments, and may have undergone multiple surgeries to restore vision while experiencing years of life-changing symptoms. OPTIC and OPTIC-X clinical trial data, and after FDA approval, we use Tepezza in the real world The observations made by TED provide very convincing reasons for completely changing the expectations of TED patients."
Thyroid ophthalmopathy (TED) is a progressive and debilitating autoimmune disease. The active disease window is limited and can be treated without surgical intervention during this period. Although TED often occurs in patients with hyperthyroidism or Grave's disease (hyperthyroidism), it is a unique disease caused by autoantigens that activate IGF-1R-mediated signaling complexes on cells in the orbit. . This will lead to a series of negative effects, causing long-term, irreversible damage. Active TED lasts up to 3 years and is characterized by inflammation and tissue expansion behind the eye. As TED progresses, it can cause serious damage, including protruding eyes (bulging eyeballs), strabismus (eyeball misalignment), diplopia (two visions), and in some cases blindness.
In the past, patients had to go through active TED until the disease became inactive (which usually left permanent and visually impaired consequences) before performing complex and expensive surgery, but surgery may never restore vision or appearance . TED patients often experience long-term functional, psychological, and economic burdens, including inability to work and engage in activities of daily living.
Tepezza’s active pharmaceutical ingredient, teprotumumab, is a fully human IgG1 monoclonal antibody that targets insulin-like growth factor-1 receptor (IGF-1R). It is developed for the treatment of moderate to severe thyroid eye disease (TED), which is usually associated with Grave's disease (Grave's disease, hyperthyroidism) is related. In the OPTIC study, patients treated with teprotumumab experienced an unprecedented reduction in exophthalmos, and this can only be treated with surgery after the end of the active disease.
The approval of Tepezza on the market provides clinicians with the first drug to reduce exophthalmos in addition to other painful symptoms during active TED. Horizon will also conduct a post-marketing study to evaluate the safety of Tepezza in a larger patient population, as discussed at the DODAC meeting on December 13, 2019. The study will also assess the relationship between the retreatment rate and the length of patient treatment
Source: Bio Valley