July 25, 2025
11 min learn
Key takeaways:
- Thyroid eye illness therapies have developed considerably lately.
- Work continues to be wanted to search out sturdy, simply administered therapies with few unwanted effects.
There was a variety of pleasure when Tepezza grew to become the primary drug accredited for the therapy of thyroid eye illness in January 2020. Then, COVID hit.
“Form of horrible timing with reference to that,” Richard C. Allen, MD, PhD, FACS, mentioned. “There was a variety of preliminary pleasure, after which all people’s clinic shut down.”
Picture: Courtesy of Richard C. Allen, MD, PhD, FACS
Regardless of this preliminary pandemic-spurred letdown, Tepezza (teprotumumab-trbw, Amgen) has modified the panorama of therapy in thyroid eye illness (TED).
“Thyroid eye illness has form of been revamped so far as how we take into consideration therapy for the illness,” Raymond S. Douglas, MD, PhD, mentioned. “Teprotumumab is now firmly in place as the one first-line therapy for the illness. There was a lot funding in different potential therapeutics that may start to get rolled out very quickly. It’s actually going to be a dynamic area over the subsequent 10 years of modifications and of us, as surgeons, getting extra snug on tips on how to deal with sufferers and adjusting to raised protocols as we’re proper in the midst of these modifications.”
Raymond S. Douglas
Having medical remedy has dramatically modified the therapy panorama for surgeons and their sufferers with TED. Healio | OSN Neurosciences Board Member Kimberly P. Cockerham, MD, mentioned there may be potential for extra innovation within the area.
“Hopefully, we’ll be taking a look at this in 5 to 10 years and we will likely be ready that, as an example, a number of sclerosis is in,” she mentioned. “There was no FDA-approved therapies, and now there’s greater than 20. You’ll be able to individualize a affected person’s care primarily based on their comorbidities and mix the drugs in ways in which prolong sturdiness.”
Cockerham mentioned there has already been an enormous change in how typically she performs surgical procedure on sufferers with TED.
“I used to do roughly 100 decompressions in a 12 months, and now, it’s very, only a few,” she mentioned. “Even then, it’s normally simply an intraconal fats elimination reasonably than drilling down bone. From a affected person standpoint, that’s actually been the most important affect as a result of fewer sufferers require large surgical procedure. Bone decompressions may end up in new or worsening strabismus. In sufferers who’ve undergone remedy with Tepezza that I do take to surgical procedure for strabismus, the muscle tissues have reverted to a way more regular look. While you do strabismus surgical procedure in a affected person with TED who has not been handled, it’s a way more difficult restore.”
Kimberly P. Cockerham
Allen mentioned Tepezza has loved a pleasant keep because the best choice for TED, and the final 5 years have taught clinicians rather a lot in regards to the drug and tips on how to greatest use it.
“The fantastic thing about that’s that we now have a better-defined aspect impact profile, which was an enormous factor early on that was regarding folks,” he mentioned. “We all know we now have to look at for listening to loss and diabetes. We are able to’t apply it to sufferers with inflammatory bowel illness. Then, there are additionally some menstrual points with ladies after they take the drug. Lots of people have been actually involved as a result of these unwanted effects weren’t very properly described from the scientific trials. After a variety of sufferers have undergone therapy, that profile is healthier outlined, and we now have tips now with reference to tips on how to display screen sufferers for these potential issues.”
Pipeline
With the success of Tepezza, different firms have taken word. The pipeline for TED consists of entries from Alumis, Immunovant, Kriya Therapeutics and extra.
“[Amgen has] had run,” Allen mentioned. “They’ve loved cornering the market with reference to the one FDA-approved remedy for TED, however different firms have seen that success and are creating medicine of their very own.”
Some medicine within the pipeline are going the identical route as Tepezza, an insulin-like development factor-1 receptor (IGF-1R) inhibitor. Veligrotug (Viridian Therapeutics), previously often called VRDN-001, was just lately granted breakthrough remedy designation by the FDA. The drug was evaluated in two part 3 trials, THRIVE and THRIVE-2.
Within the THRIVE trial, 75 sufferers with lively TED obtained veligrotug and 38 obtained placebo. All sufferers had average to extreme TED, proptosis of at the very least 3 mm and a scientific exercise rating of at the very least 3. All obtained intravenous infusions each 3 weeks for 5 complete infusions (final infusion at week 12).
Sufferers within the veligrotug group had higher proptosis response and imply change in proptosis in addition to diplopia response and backbone; additionally, scientific exercise rating discount was higher in contrast with sufferers within the placebo group.
The THRIVE-2 examine comprised 125 sufferers with power TED who obtained veligrotug and 63 who obtained placebo. On the 15-week main endpoint evaluation, sufferers within the therapy group had higher outcomes in proptosis, diplopia, scientific exercise and total response.
“It has very related outcomes with reference to what we’re seeing in contrast with Tepezza,” Allen mentioned. “The distinction between the medicine is fewer administrations with the Viridian drug in contrast with Tepezza. One of many issues we’ve witnessed with Tepezza is that individuals don’t like going to infusion facilities. That’s the reason there was focus on making an attempt to get subcutaneous formulations of the drug.”
Viridian can also be engaged on a subcutaneous agent referred to as VRDN-003, and it initiated two part 3 trials in 2024.
“A few of our colleagues have infusion facilities of their workplaces, and there are undoubtedly monetary incentives to have an infusion heart,” Allen mentioned. “However I feel many people could be snug administering a subcutaneous formulation. Then, I feel the thought could be that the affected person would administer it themselves at dwelling.”
Success of subcutaneous IGF-1R brokers will come right down to security profiles, Allen mentioned.
Douglas referred to as the event of latest IGF-1R medicine a widening of medical administration of sufferers with TED. The molecules could be related, however choices could make a distinction, particularly with regards to administration. He mentioned one other related molecule in growth is linsitinib (Sling Therapeutics), however as an alternative of IV or subcutaneous administration, it’s an oral molecule.
“What we’re rising towards is complementary therapies which are actually going to have the ability to handle sufferers all through your complete course of TED,” he mentioned.
Linsitinib was evaluated within the part 2b/3 LIDS trial in sufferers with lively average to extreme TED. Sufferers have been randomly assigned to obtain linsitinib 150 mg twice day by day, linsitinib 75 mg twice day by day or placebo for twenty-four weeks. Sling mentioned the trial achieved its main endpoint of proptosis discount at week 24, with a proptosis response price of 52% with the 150 mg dose.
Allen mentioned an oral remedy has the potential to handle the unwanted effects of different IGF-1R therapies.
“The large query is, what’s the mechanism of those unwanted effects? Is it resulting from peak drug concentrations within the serum? While you give somebody an infusion, you’re giving an enormous dose that you simply’re hoping will final for 3 weeks,” Allen mentioned.
“These are the issues to consider with reference to oral remedy,” he mentioned. “Because you’re taking it each day, you’re form of having a upkeep dose, a comparatively low focus that hopefully will keep away from a few of these unwanted effects that we expect could also be associated to peak drug concentrations.”
Cockerham mentioned it has been attention-grabbing to see the opposite pathways firms are taking a look at for TED therapies.
“They’re wanting on the contribution of cell markers apart from IGF-1,” she mentioned. “IL-6, IL-11 and neonatal Fc receptor inhibitors are all being studied now. It is going to be attention-grabbing to see if blocking different receptors will alter the pathologic cell-to-cell signaling as a lot as blocking IGF-1 does.”
Douglas mentioned that clinicians specializing in TED may have a full complement of choices within the close to future.
“Totally different phases of the illness require completely different choices,” he mentioned. “For instance, if somebody has very extreme illness, teprotumumab could also be an excellent remedy. Nonetheless, if somebody has extra gentle illness, they could not need to tackle the unwanted effects of that remedy, they usually might go for one thing completely different if they’re very early within the illness or if they’ve a reactivation of the illness. A number of the IL-6 blocking brokers sooner or later may be capable of get rid of that with a dose or two. We will tailor these drugs all all through the illness course of. Proper now, a really small proportion of sufferers are literally handled with medical remedy. Over time, that may improve simply because the drugs will likely be extra various and have fewer unwanted effects.”
Collaboration with endocrinology
Douglas mentioned working with endocrinologists is essential to handle sufferers by means of each step of their illness journey. In a big majority of sufferers, thyroid points current first, so sufferers will work with the endocrinologist earlier than seeing an ophthalmologist.
“Graves’ illness or hyperthyroidism presents first, after which over a time period, usually 6 to 12 months, they may develop eye illness,” Douglas mentioned. “The endocrinologist typically sees the affected person first, takes proactive, preventive measures, after which will ship them to a thyroid eye illness specialist or ophthalmologist.”
Douglas mentioned this partnership is significant to his apply and can probably solely turn out to be extra essential.
“As we now have increasingly more drugs, sufferers generally have hyperglycemia or different endocrinologic manifestations or modifications resulting from these drugs,” he mentioned. “I associate with endocrinologists from the very starting, and it’s a really very important a part of my apply. I allow them to know the way I’m managing the affected person, and they’re going to inform me what they’re doing. It’s a fixed forwards and backwards the place the endocrinologist is seeing the affected person each 3 to six months. These notes and that collaboration is extremely essential as we transfer ahead, particularly with the medical therapies.”
Terry F. Davies, MBBS, MD, FRCP, FACE, an endocrinologist and professor at Icahn Faculty of Medication at Mount Sinai, mentioned the 2 specialists have completely different focuses with regards to TED, however they should work collectively to offer one of the best outcomes for sufferers.
Terry F. Davies
“The endocrinologist will take care of the thyroid, however the ophthalmologist will be sure that the eyes are secure and will be handled appropriately,” he mentioned. “The entire world has modified with the introduction of Tepezza. It’s the primary drug to truly put the eyes again within the head few millimeters. The ophthalmologist doesn’t must resort to decompression surgical procedure wherever close to as a lot as prior to now. Nonetheless, for the administration of most sufferers with Graves’ illness, they don’t have unhealthy eyes. They’ve gentle illness. Apart from a routine eye examination, which everybody ought to get anyway, there isn’t rather a lot for the ophthalmologist to do.”
When the illness begins to shift towards the average to extreme finish of the spectrum with proptosis, irritation and ache, that’s when Davies will ship a affected person for ophthalmology evaluation.
“Now, who really initiates the therapy and follows the attention is considerably in dispute,” he mentioned. “I’m very pleased for the ophthalmologist to try this with me so long as it’s really with me and never on his or her personal. It’s a quickly transferring goal proper now, and we don’t like that as a result of ophthalmologists can’t handle the thyroid. Most of those sufferers will likely be on anti-thyroid medicine, they usually must be monitored fastidiously. Nonetheless, typically, it’s a beautiful interplay as a result of each physicians have an interest within the illness, they usually each need to assist the affected person and make them higher.”
Davies mentioned one in every of greatest boundaries with collaboration on TED is the separation of companies. In some international locations, each specialists are in a position to work collectively inside a mixed clinic, however as a result of present reimbursement system within the U.S., he doesn’t suppose this mannequin would work.
“Most ophthalmologists see 20 sufferers in a day at the very least, and one in every of these sufferers with TED can take a couple of hours of their time,” he mentioned. “We find yourself seeing the affected person in our clinic and referring them to a pleasant ophthalmologist who sees them at one other time.”
A joint clinic “can solely work if the ophthalmologist isn’t being penalized for under seeing a couple of sufferers,” Davies mentioned.
Future wants
Whereas Tepezza has been a recreation changer, it’s not with out points, Cockerham mentioned.
“It’s costly, and a few sufferers are getting two rounds,” she mentioned. “That could possibly be costing the well being care system within the vary of $300,000 to $600,000 or extra.”
She mentioned there are additionally sturdiness considerations, with lower than 20% of sufferers experiencing recurrence requiring further therapeutics: Over 99 weeks following teprotumumab remedy, 19 of 106 sufferers (17.9%) reported further TED remedy throughout formal and prolonged follow-up.
“Then you definitely’ve additionally acquired the price of the infusion heart itself. If any of those medicine can transfer towards being injected, then they may also reduce the price to the well being care market,” she mentioned. “It’s very thrilling that there’s so many pharmaceutical firms at the very least wanting on their shelf and asking, ‘Do we now have an IL-6 blocker? Do we now have an IGF-1 blocker? Is there one other mechanism of motion that could be contributory to enhancing the scientific indicators and signs of thyroid eye illness?’”
Regardless of all the thrill, Allen mentioned there may be nonetheless work to do.
“We’ve got made a variety of advances with reference to the understanding of the pathophysiology of the illness and the completely different pathways that may be focused,” he mentioned. “However are we there but? We’re not there. We nonetheless have an extended method to go earlier than we deal with this illness successfully with remedy that targets the precise difficulty that’s happening within the particular affected person that’s going to be sturdy, has few unwanted effects, is simple to manage and is cost-effective.”
Davies mentioned a lot has modified over the 40 years he has handled sufferers with TED. He mentioned he used to have hassle getting them seen by ophthalmologists, and now, each ophthalmologist is excited by treating them. Having higher affected person consciousness has helped as properly.
“Individuals know what’s happening, and there’s a therapy accessible,” he mentioned. “Our job as physicians is to reassure the affected person that, sure, you’ll get there. You’ll be OK. You go from A to Z, however getting from A to Z is usually a bit of labor, and there will be stops on the best way, however finally the eyes will begin to look rather a lot higher.”
References:
- Abrams J, et al. Efficacy and security of veligrotug (VRDN-001), a full antagonist monoclonal antibody to IGF-1 receptor, in lively thyroid eye illness (TED): THRIVE part 3 topline outcomes. Offered at: American Affiliation of Medical Endocrinology annual scientific and scientific convention; Might 15-17, 2025; Orlando.
- Kahaly GJ, et al. Thyroid. 2024;doi:10.1089/thy.2023.0656.
- Sling Therapeutics broadcasts constructive topline outcomes from part 2b/3 LIDS scientific trial of oral small molecule linsitinib in sufferers with thyroid eye illness. https://www.slingtx.com/2025/01/14/sling-therapeutics-announces-positive-topline-results-from-phase-2b-3-lids-clinical-trial-of-oral-small-molecule-linsitinib-in-patients-with-thyroid-eye-disease/. Printed Jan. 14, 2025. Accessed July 10, 2025.
- Turbin RE, et al. THRIVE-2 part 3 trial of veligrotug (VRDN-001) in power thyroid eye illness (TED): Efficacy and security at 15 weeks. Offered at: American Affiliation of Medical Endocrinology annual scientific and scientific convention; Might 15-17, 2025; Orlando.
- Viridian Therapeutics broadcasts constructive topline outcomes from veligrotug (VRDN-001) part 3 THRIVE scientific trial in sufferers with lively thyroid eye illness. https://buyers.viridiantherapeutics.com/information/news-details/2024/Viridian-Therapeutics-Broadcasts-Constructive-Topline-Outcomes-from-Veligrotug-VRDN-001-Part-3-THRIVE-Medical-Trial-in-Sufferers-with-Energetic-Thyroid-Eye-Illness/default.aspx. Printed Sept. 10,2024. Accessed July 10, 2025.
For extra info:
Richard C. Allen, MD, PhD, FACS, of Baylor Faculty of Medication, will be reached at richardcutlerallen@gmail.com.
Kimberly P. Cockerham, MD, director of neuro-ophthalmology at Brady Neuroscience Clinic, San Diego, will be reached at cockerhammd@gmail.com.
Terry F. Davies, MBBS, MD, FRCP, FACE, of Icahn Faculty of Medication at Mount Sinai, will be reached at terry.davies@mssm.edu.
Raymond S. Douglas, MD, PhD, of Cedars-Sinai, will be reached at raymonddouglasmd@gmail.com
Sources/Disclosures
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Healio Interviews
Disclosures:
Davies experiences being on the board for Kronus and consulting for Amgen, Biohaven, Immunovant and Regeneron. Douglas experiences being chief scientific officer of RVL Prescription drugs and Sling Therapeutics.
