Viridian aims to prove itself in thyroid eye
Forthcoming data will see the group take on Horizon, but subcutaneous projects could pose the real threat.
Horizon Therapeutics’ Tepezza is the only drug approved for thyroid eye disease, and last week its reach increased. In the wake of data suggesting Tepezza works in patients with chronic but mild disease, the FDA approved a change to the drug’s label, specifically stating that it can be used “regardless of thyroid eye disease activity or duration”.
Whether payers will expand reimbursement to match is another question, though with Amgen's takeover of Horizon in the works powerful marketing muscle could soon be brought to bear. What is not in question, however, is that a competitor is hard on Horizon’s heels. Viridian Therapeutics will shortly report mid-stage data on VRDN-001 in both chronic TED, and success could begin to change the landscape.
|% of market cap||167%|
|Event type||Phase 1/2 results|
Data from two trials of VRDN-001, which like Tepezza is an IGF-1R blocker, ought to emerge in the next couple of months. The most commercially important will be the phase 3 readout in patients with severe active TED, due in early 2024.
The Thrive trial is more than twice the size of Tepezza’s approval trial in the severe active population, Optic, but has similar enrolment criteria and the same primary endpoint – proptosis responder rate (PRR) after six months’ treatment. Thus experts and investors alike will be looking for a result that matches or exceeds the 73% treatment effect seen in Optic.
Viridian has not released a great deal of data from its phase 1/2 study of VRDN-001 in this setting, but the results included in a company presentation show that 11 of 16 evaluable VRDN-001 recipients hit the 2mm improvement in proptosis that defined response, versus none of the five placebo subjects, after six weeks' treatment. With 21 patients in the treatment group this gives a placebo-adjusted PRR of 52% in the ITT population. The tiny patient numbers and different time point, however, make it hard to deduce what this might mean for the Thrive trial.
Ah, go on, TED
The more immediate big readout, which is coming this quarter, is from the phase 1/2 trial of VRDN-001 in subjects with mild, long-term TED – a similar group to that enrolled in the phase 4 trial in which Tepezza just succeeded. The study consists of two cohorts of eight patients each, who will receive either two doses of 3mg/kg or 10mg/kg every three weeks, as well as two patients given placebo.
Some analysts regard Horizon’s phase 4 data as de-risking the readout. Despite the differences between Horizon’s and Viridian’s chronic studies – which include dosing, treatment duration and disease severity – SVB analysts believe that VRDN-001 could differentiate itself from Tepezza in the commercially important chronic, mild TED population.
Viridian’s former chief executive Jonathan Violin has previously told Vantage that compared with Tepezza VRDN-001 might have “faster onset, earlier symptom relief, potentially higher efficacy, shorter course of treatment, all of which we think will come in a package with a very attractive safety profile.”
|The bar for Viridian in thyroid eye disease|
|Project (company)||Tepezza (Horizon)||VRDN-001 (Viridian)|
|Trial||Ph3 (Optic, NCT03298867)||Ph4 (NCT04583735)||Ph 1/2||Ph2/3 (Thrive, NCT05176639)||Ph1/2|
|Population||Moderate-to-severe active TED||Mild, chronic TED||Moderate-to-severe active TED||Moderate-to-severe active TED||Mild, chronic TED|
|CAS||≥ 4||≤ 1||≥ 4||≥ 4||≤ 7|
|Duration of disease||< 9mth||2-10yrs||< 1yr||< 1yr||> 1yr|
|Proptosis||n/a||≥ 3mm||n/a||n/a||≥ 3mm|
|Primary endpoint||PRR||Change in proptosis||Unknown||PRR||Unknown|
|Pbo-adj PRR in ITT pop||73% (p<0.001)||37% (p=0.0134)||Data expected Q2 2024||Data expected Q2 2023|
|Pbo-adj chg in proptosis in ITT pop||2.79mm||1.49mm (p=0.0004)|
|CAS=clinical activity score. PRR=proptosis responder rate; proptosis response defined as reduction of at least 2mm. All data at 24wk. *Vantage calculation. Source: NEJM, clinicaltrials.gov, company communications.|
Another chance for Viridian to distinguish itself is with a subcutaneous TED therapy. The group is working on a subcutaneous form of VRDN-001, but also on two other candidates, -002 and -003. Early clinical data on all three should arrive by the end of the year, and then Viridian will decide which to take forward. Horizon is developing a subcutaneous form of Tepezza, too.
Wells Fargo analysts believe the convenience of a subcutaneous offering could play a major role, particularly in chronic TED.
Sling Therapeutics and Acelyrin are the other groups known to be exploring IGF-1R inhibition in TED, and Sling’s therapy, the only oral small molecule in the clinic with this mechanism, could prove a contender if its mid-stage study succeeds later this year.
Currently the sellside forecasts 2028 sales of $989m for VRDN-001, versus $4.2bn for Tepezza. By the summer, it will be clear whether Viridian might close that gap – though if the Amgen-Horizon deal goes through Viridian will be up against a major competitor.
|IGF-1R therapies for active and chronic TED|
|Horizon||Tepezza||IV||Approved in US since 2020; recent ph4 data could expand use into mild, chronic patients|
|Tepezza SC||SC||Ph1 began Jul 2022|
|Viridian||VRDN-001||IV||Ph3 Thrive trial in moderate-to-severe active TED and Ph1/2 in mild, chronic TED could report Q2 2023|
|VRDN-001 SC||SC||Ph1 planned; data expected 2023|
|VRDN-002||SC||Ph2 data expected 2023|
|VRDN-003||SC||Ph1 planned; data expected 2023|
|Sling Therapeutics||Linsitinib||Oral||Ph2b Lids trial in active, moderate-to-severe TED could report 2023|
|Acelyrin (formerly Valenzabio)||Lonigutamab (VB421)||SC||Ph1/2 trial in severe, active TED could report 2024|
|Source: Evaluate Pharma, clinicaltrials.gov, Viridian presentation.|
Note: text has been updated to correct time point of data from Viridian's phase 1/2 trial in moderate-to-severe active TED; data was also removed from the table.