Viridian Drug Meets Main Goals in TED Trial, but Shares Sink on Results

Rare Daily Staff

Viridian Therapeutics said its experimental drug elegrobart met the main goals of a late-stage study in people with active thyroid eye disease, a condition that can cause eye bulging and double vision.

Despite the positive results, shares of Viridian fell sharply because the data raised safety concerns related to hearing impairment, even though the rates were low. Shares of Viridian traded as low as $16.97, down from a previous close of $27.39.

Thyroid eye disease (TED) is an autoimmune inflammatory disorder in which immune attack on tissues around and behind the eyes—most often in people with Graves’ hyperthyroidism—causes swelling of orbital fat and muscles, leading to eye redness, pain, bulging (proptosis), eyelid retraction, dryness or tearing, and sometimes double vision or, in severe cases, vision loss.

Elegrobart is a half-life–extended monoclonal antibody that targets the insulin-like growth factor-1 receptor, or IGF-1R, a validated pathway in thyroid eye disease. In the phase 3 REVEAL-1 trial, patients who received subcutaneous elegrobart every four weeks or every eight weeks saw significantly greater improvements in eye bulging, or proptosis, than those given placebo at 24 weeks, the company said.

Among 132 patients in the study, 44 were assigned to elegrobart every four weeks, 44 to elegrobart every eight weeks, and 44 to placebo. In the every-four-week group, 54 percent of patients met the U.S. Food and Drug Administration’s definition of a proptosis responder, compared with 18 percent on placebo, a difference Viridian said was highly statistically significant.

The every-eight-week regimen performed similarly, with a 63 percent responder rate versus 18 percent on placebo. The company also reported improvements in double vision. In the every-four-week arm, 71 percent of patients were considered diplopia responders, compared with 32 percent on placebo, and complete resolution of double vision was seen in 51 percent of patients versus 16 percent on placebo at week 24. In the every-eight-week arm, 54 percent of patients were diplopia responders, and 28 percent achieved complete resolution, compared with 32 percent and 16 percent, respectively, on placebo.

On magnetic resonance imaging, elegrobart also demonstrated reductions in eye bulging. In the every-four-week group, 50 percent of patients met the MRI-based proptosis response criteria, compared with 2 percent in the placebo group, while 36 percent of patients in the every-eight-week group met the MRI response criteria versus 2 percent on placebo. Mean reductions in proptosis on MRI were about 2 mm in both elegrobart arms, compared with 0.22 mm on placebo. Elegrobart was “generally well tolerated,” Viridian said, with side effects broadly consistent with the anti–IGF-1R drug class and mostly mild in severity.

Hearing-related side effects—an issue for some existing therapies targeting the same pathway—were reported at low rates, with placebo-adjusted rates of hearing impairment of 11.3 percent in the every-four-week arm and 2.3 percent in the every-eight-week arm, all cases described as tinnitus without measured hearing loss.

“Currently, the only marketed treatment for TED requires eight intravenous infusions and, despite low market penetration, annualized in 2025 to approximately $2B in revenues,” Steve Mahoney, Viridian’s president and CEO, said in a statement. “We believe there is a significant opportunity with subcutaneous elegrobart in TED, including the potential to expand the market as an at-home and self-administered treatment option, if approved.”

Photo: Steve Mahoney, Viridian’s president and CEO