Viridian takes on Horizon
Early data in thyroid eye disease impress, but unanswered questions include the size of the market.
Horizon Therapeutics has had the thyroid eye disease space to itself for a couple of years, but competition could soon be coming. And Viridian’s contender VRDN-001 might have the edge when it comes to efficacy, early data released yesterday suggest.
Viridian’s stock shot up 49%, but there are several reasons to be cautious. For one, the proof-of-concept results came from just six patients receiving VRDN-001. Second, there are questions about the size of this market after Horizon recently reported disappointing second-quarter results and cut near-term guidance for its thyroid eye disease drug Tepezza.
Horizon still insists that Tepezza can bring in over $3.5bn per year at peak, but investors do not seem to share management’s enthusiasm, with the group’s stock at a one-year low. Nevertheless, Horizon is worth a chunky $15bn.
Viridian clearly wants a piece of this action, and was keen to show how data from its phase 1/2 study of VRDN-001 in active thyroid eye disease stacked up against results with Tepezza. And, with the usual caveats about cross-trial comparisons, the Viridian project does look better on measures including proptosis – eye bulging – at six weeks.
|The battle of the IGF-1R inhibitors in thyroid eye disease – a cross-trial comparison|
|Trial||Ph1/2 (NCT05176639)||Ph3 Optic (NCT03298867)|
|N (treatment arm)||6||41|
|Dose||10mg/kg; 2 infusions 3wks apart||1st infusion 10mg/kg, then 7 20mg/kg infusions every 3wks|
|Change from baseline in proptosis at wk 6||-2.4mm||-2mm|
|Proptosis responder rate at wk 6*||83%||56%|
|Overall responder rate at wk 6**||83%||44%|
|*Defined as a reduction in proptosis of ≥2mm from baseline; **defined as a ≥2mm reduction in proptosis and a ≥2 point reduction in clinical activity score. Source: company presentation & NEJM.|
The phase 3 Optic study of Tepezza ran for 24 weeks, by which time proptosis reduction had reached 3.3mm, and proptosis response was at 83%.
Tepezza and VRDN-001 are both antibodies against the insulin-like growth factor type I receptor (IGF-1R); however, Viridian claims that its project is a more complete antagonist than Tepezza. This, it says, explains the improved efficacy with VRDN-001.
This apparent advantage will have to be borne out in bigger studies. The latest efficacy data with VRDN-001 came from one dose cohort, 10mg/kg, comprising six patients receiving drug and two receiving placebo. The study also includes 3mg/kg and 20mg/kg dose arms, with efficacy data from both expected in the fourth quarter.
A new cohort, of chronic patients, is set to start by the end of this year. Viridian reckons the chronic, or inactive, thyroid eye disease market is much bigger, affecting over 75,000 US patients versus the 25,000 or so with active disease.
VRDN-001’s real test will come in phase 3, of course. The Thrive study, in active, and Thrive-2, in chronic thyroid eye disease, should both read out in 2024. Both will test 10mg/kg, given via either eight infusions – the same number as with Tepezza – or five infusions. Good data with the latter regimen could give VRDN-001 another edge over Tepezza, by offering a shortened treatment course.
Next in line
Even if VRDN-001 makes it to market, SVB analysts only see peak sales of $730m. They have higher hopes for the group’s follow-on assets: VRDN-002, a subcutaneous partial IGF-1R inhibitor with an extended half-life; and VRDN-003, a subcutaneous project that aims to combine the best of both worlds, being a full IGF-1R antagonist with an extended half-life.
Viridian plans to decide next year which of these to take forward. And it is not the only group aiming to eclipse Tepezza. Valenzabio says its asset VB421 is the most potent anti-IGF-1R antibody in development; first-in-human data are expected this quarter.
Valenzabio – and Viridian – still have much to prove, but it seems certain that Horizon’s thyroid eye disease monopoly will soon be under threat.