Viridian targets Horizon’s Tepezza with chronic thyroid eye disease data, setting up the biotech for its second PhIII

Viridian Therapeutics said its IV-administered antibody led to clinical improvements in a small group of patients with the chronic form of thyroid eye disease, as it looks to take on Horizon Therapeutics’ Tepezza.

The Phase I/II results give the Waltham, MA-based biotech confidence to begin its second Phase III trial of VRDN-001. With one late-stage study already underway in active TED, Viridian will also run a Phase III in chronic TED so the two trials can serve as the backbone of a submission to the FDA, Viridian CEO Scott Myers told Endpoints News.

Investors reacted cooly, sending shares $VRDN down about 20% right after the closing bell when the news was announced publicly.

Thyroid eye disease, or TED, is a rare autoimmune disease that affects more than 250,000 people in the US and Europe. It can lead to double vision and sometimes blindness, and inflammation spurred by TED can lead to bulging of the eyes and ocular pain.

Viridian tested two infusions, given three weeks apart. Six patients received 10 mg/kg and another six got 3 mg/kg. Five patients received placebo. No serious adverse events were reported, Viridian said.

At week six, investigators used a device called an exophthalmometer to measure changes in patients’ eye bulging, formally known as proptosis, from baseline. They recorded mean reductions of 1.8 mm and 1.5 mm, respectively.

Ahead of the data, Jefferies analyst Michael Yee said he’d like to see a 1.2 mm to 1.5 mm reduction. A reduction in that range could lead to a stock gain and give investors more confidence in the program, he wrote in a June 18 note.

In Horizon’s later-stage study of Tepezza in patients with chronic TED, the biotech recorded an approximately 1.2 mm reduction after two infusions and about 2.41 mm after a total of eight infusions at 24 weeks. A few days after Tepezza’s data came out in April, the FDA expanded the drug’s original 2020 indication to include patients with both active and chronic TED. Both VRDN-001 and Tepezza go up against the insulin-like growth factor-1 receptor, or IGF-1R.

Like all cross-trial comparisons, there are caveats: Horizon and Viridian enrolled patients at different stages of their disease and with varying levels of inflammation at baseline.

Thomas Ciulla

“We’ve seen this consistency now across both acute and chronic populations where VRDN-001 shows a better response, frankly, than tepro [Tepezza] after two infusions,” Viridian development chief Thomas Ciulla told Endpoints.

Viridian also looked at the proptosis changes using magnetic resonance imaging, which it considers a more precise measurement, though it won’t be used as a main endpoint in future clinical trials because the FDA views exophthalmometry as a validated endpoint. The MRI data showed reductions of 1.5 mm and 2.6 mm, respectively, but data were not available for four of the 12 VRDN-001-treated patients.

For the five patients in the placebo group, the mean reduction in proptosis was 0.2 mm as viewed by MRI. Viridian did not share placebo data on the exophthalmometry measurement.

“For exophthalmometry, you have a lot of inherent variability in that test, so a placebo group of only two patients really is meaningless when you have exophthalmometry,” Ciulla said.

Viridian said five of 12 patients on VRDN-001 had double vision at baseline, but none achieved complete resolution at week six.

Beyond Viridian and Horizon, the biopharma field is ripe with TED R&D, including work at Tourmaline Bio, Immunovant, argenx, UCB, Astellas, Acelyrin and multiple other drug developers. Tepezza brought in $1.9 billion in sales last year and and is a focus of the FTC’s lawsuit against Amgen’s proposed $28 billion takeover of Horizon.

Viridian’s two late-stage trials in active and chronic TED are slated to read out in the middle and final stretch of 2024, respectively. Viridian also said it dropped the eight-dose treatment regimen to focus on a five-dose regimen, based on stakeholder preference for a shorter duration of treatment and recent talks with the FDA.

Barrett Katz

Medical chief Barrett Katz said the dosing adjustment was not made based on safety reasons but rather feedback from treating physicians and the existing Tepezza market.

“We recognize that in addition to the burden of the disease, there’s a major burden of treatment, and if we could shorten the number of infusions and reach equal success with a smaller dose, which we are with a 10 mg dose, the patients would be best served,” Katz said.

Viridian aims to quickly follow up with a subcutaneous treatment for TED as well. By the end of the year, the biotech will choose one of its three subcutaneous options to take into a Phase II/III trial in the middle of next year. Those options include VRDN-002, VRDN-003 and an under-the-skin version of VRDN-001.

Asked if the company plans to follow the data-to-public-offering path like multiple other biotechs have done, Myers said Viridian is well-financed. It raised about $175 million in August after sharing the active TED data. In May, Viridian said it had enough money to bankroll operations into the back half of 2025.

Editor’s note: This story was updated to include share price reaction.

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