Thyroid eye disease medicine 'Tepezza' lands in Korea

The first TED-targeted therapy emerges in South Korea…expected to reduce the treatment gap

Competition among IL-5R and drugs with follow-up mechanisms intensifies while FcRn new drug candidates face clinical struggles

Targeted therapy for thyroid eye disease (TED) 'Tepezza'

Changes in treatment strategies are expected as the first targeted therapy for thyroid eye disease (TED) enters the Korean market.

With follow-up candidates still in development or facing clinical hurdles with certain mechanisms, the possibility has been suggested that the market will remain centered on Amgen's already-commercialized Tepezza (teprotumumab).

According to industry sources on the 7th, Amgen Korea recently obtained marketing authorization from the Ministry of Food and Drug Safety (MFDS) for Tepezza. The approved indication is for the treatment of adult patients with moderate-to-severe TED.

TED is a rare disease in which autoimmune reactions cause inflammation and swelling of the orbital tissues. It causes proptosis, double vision, eye pain, and vision loss. If the disease progresses to a severe stage, it can lead to permanent disfigurement or even the risk of blindness.

Until now, treatment in Korea has centered on symptomatic therapies such as steroids, radiation therapy, and orbital decompression surgery. However, critics have consistently pointed out that these have limitations in restoring structural changes such as proptosis or double vision.

Tepezza is a monoclonal antibody that targets the Insulin-like Growth Factor-1 Receptor (IGF-1R), a key pathogenic mechanism in TED. It differentiates itself from existing treatments by targeting the disease to suppress the inflammatory response and tissue expansion.

In the global Phase 3 OPTIC study, the proptosis response rate (a reduction of 2 mm or more) at 24 weeks was 83% for the Tepezza group and 10% for the placebo group. The diplopia (double vision) improvement rate also recorded 68% and 29%, respectively.

In the OPTIC-J study of Japanese patients, the proptosis response rate was 89% in the Tepezza group and 11% in the placebo group.

Tepezza already obtained regulatory agency authorization in the U.S. in 2020 and is currently the only approved targeted therapy for TED.

FcRn inhibitors face  hurdles… Delayed follow-up competition

Subcutaneous (SC) formulation 'Vyvgart (efgartigimod)'

The competitive landscape for TED-targeted therapies remains limited, even in the global market.

In particular, new drug candidates in the FcRn inhibitor class, which targeted to enter the TED market by reducing autoantibodies, are facing successive clinical barriers.

Inhibition of the neonatal Fc receptor (FcRn), the protection receptor for Immunoglobulin G (IgG), is an approach that blocks the recycling pathway of IgG antibodies, thereby lowering the levels of pathogenic antibodies. It is evaluated as a treatment strategy applicable to autoimmune diseases in general. However, it appears to be struggling in the field of TED, beyond myasthenia gravis.

HanAll Biopharma’s global partner, Immunovant, recently announced that its FcRn inhibitor batoclimab (IMVT-1401) failed to meet its primary endpoint in a global Phase 3 trial for TED. It failed to secure statistical significance in improving the Proptosis Responder Rate.

Belgium-based Argenx also discontinued its clinical research on the FcRn inhibitor 'Vyvgart (efgartigimod)' for TED. Development was halted as the Independent Data Monitoring Committee (IDMC) judged the possibility of meeting the primary endpoints to be low.

Accordingly, expert analysis suggests that a simple approach of reducing autoantibodies alone may be difficult to achieve sufficient clinical effects in TED.

Chase by Viridian and Roche…the competition continues

New drug development has not stagnated entirely. Among the followers, the most advanced is U.S.-based Viridian Therapeutics. Viridian is developing 'elegrobart,' a candidate based on the same IGF-1R mechanism as Tepezza.

Elegrobart recently confirmed improvements in proptosis and diplopia in a global Phase 3 trial for patients with chronic TED, demonstrating the fastest rate of improvement among follow-up candidates.

Roche’s 'Enspryng' 

However, Amgen has also moved to defend its market, recently reporting positive results from a Phase 3 trial of a subcutaneous (SC) formulation of Tepezza using an on-body injector (OBI). Consequently, competition in the TED market appears to be shifting toward competing for both efficacy and convenience, rather than simply SC conversion.

Competition based on other mechanisms is also continuing. Roche’s 'Enspryng (satralizumab)' is a treatment that blocks the Interleukin-6 (IL-6) receptor, which is involved in inflammatory responses.

Enspryng differs from the IGF-1R class, which directly targets ocular tissue expansion, by targeting the disease by suppressing orbital tissue inflammation and immune responses in TED.

Roche recently announced positive results from the global Phase 3 SatraGO program for TED and disclosed plans to apply for authorization within the year.

Enspryng failed to achieve statistical significance for the primary endpoint in the global Phase 3 SatraGO-1 study in patients with active TED. However, a pooled analysis with the follow-up Phase 3 study, SatraGO-2, reportedly confirmed a proptosis improvement effect.

Until now, the treatment with the clearest clinical efficacy in TED has been the IGF-1R-targeted therapy. As FcRn inhibitors face successive clinical struggles, follow-up competition is trending toward a reorganization around IL-6R inhibitors and next-generation IGF-1R agents.