New phase 3 data paints fuller picture for Horizon’s teprotumumab: AACE

On the back of a successful phase 3 study, Horizon Pharma said in February that its inflammatory eye drug was headed for an FDA filing midyear. Now, the company is presenting new data from that study that dig deeper into how fast the drug works and how it stacks up against the current treatment: eye surgery. 

The drug, teprotumumab, is an inhibitor of the insulin-like growth factor type 1 receptor that Horizon Pharma is developing to treat thyroid eye disease (TED), a rare autoimmune, inflammatory disorder that often accompanies endocrine disorders like overactive thyroid. Patients tend to see a doctor when they notice their eyes bulging in photos, or that their eyes and eyelids constantly seem to be red and swollen, Raymond Douglas, M.D., Ph.D., of Cedars-Sinai Medical Center, told FierceBiotech. Douglas was one of the leaders of the study and presented the data at the American Association of Clinical Endocrinologists’ annual meeting in Los Angeles.

"These facial changes happen during what we call the active phase of the disease," he said. This period of active inflammation lasts about two to three years before TED stabilizes. While patients with inactive TED may undergo surgery to treat symptoms such as double vision and eye bulging, there are no approved treatments for the active period of the disease.

"Steroids are used to make the swelling look better and make it go away for a bit, but it’s like giving Advil for a swollen ankle. It makes it feel better, but it doesn’t make you able to run a marathon the next day," Douglas said. 

Teprotumumab may not be an instant bridge to marathons for TED patients, but it could get them back outside. Patients tend to withdraw from social activities and stay indoors for two reasons: the way their eyes look and the fact that eye bulging—which leads to the eyelid retracting—means they have no way to protect their eyes from the elements, said Douglas and Shao-Lee Lin, M.D., Ph.D., Horizon’s chief scientific officer and head of R&D. 

The updated data showed that after 24 weeks, patients taking teprotumumab had, on average, a 2.82-mm reduction in eye-bulging, compared to 0.54mm in patients on placebo. That decrease is on par with a procedure called size decompression surgery that moves the eyeball back into a normal position in the eye socket. 

"It’s a surgery I do every day: I make a little incision in the eyelid crease, go behind the eyeball and start shaving the bone between the eye and the brain," Douglas said. When he’s done, in about one and a half hours for each eye, Douglas said there could be a 3-mm reduction in bulging. 

Data from a phase 2 study showed that the drug reduced double vision and swelling in the eyelid and muscles around the eye. Combined with its effects on eye bulging and the fact that patients don’t have to undergo a skull-shaving procedure, "that 2.8mm doesn’t look so bad," Douglas said. 

Teprotumumab also outperformed placebo at reducing bulge at various points of the study: at weeks 6, 12, 18 and 24. 

"This tells us it is working very fast; we don’t need to wait six months to see if it’s working. From a science point of view, it means we’re probably hitting the right mechanism at the right time point in the active phase," Douglas said. 

Of the patients who received teprotumumab, 78% of them responded to the treatment; that is, their eye bulging decreased at least 2mm and their Clinical Activity Score—a measure of swelling—dropped at least two points. This figure for the placebo group was 7%. 

A few of the patients taking placebo did see improvements in swelling and eye bulging, but that’s to be expected, Douglas said. As a person’s disease evolves over the active period, it may bounce back a little before it stabilizes. 

"No one comes back to normal, but sometimes you get a little improvement," he said. 

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