A novel intravitreal anti-IL-6 monoclonal antibody for UME: preliminary results from the phase 1 DOVETAIL study

Theme: Uveitis
What: Uveitis
Part of: Uveitis II: Advancements in Uveitis Diagnosis and Management / Uvéite II: Avancées dans le diagnostic et la prise en charge de l’uvéite
When: 5/31/2024, 02:00 PM - 03:30 PM
Where: Room | Salle 714 B

Abstract

Purpose:

The DOVETAIL phase 1 clinical trial assessed the safety, tolerability and efficacy of a novel anti–IL-6 monoclonal antibody (RG6179) specifically designed for IVT use in patients with DME and UME.

 

Study Design:

DOVETAIL is a phase 1, multicenter, non-randomized, open-label, multiple ascending dose study that investigates the safety, tolerability, efficacy, and PK/PD profile of RG6179 in both DME and UME patients.

 

Methods:

Inflammation is a key pathway in retinal disease pathophysiology. However, standard-of-care anti-inflammatory corticosteroid use carries significant risk of side effects. RG6179 is a recombinant monoclonal antibody that potently inhibits all forms of IL-6 signalling. This abstract reports the      preliminary data with RG6179 in patients with UME. Patients ≥18 years with non-infectious uveitis and concurrent ME (CST ≥325 µm) were included (N=33). Patients were enrolled into 3 dose groups: 0.25 mg (n=10), 1 mg (n=10), and 2.5 mg (n=13), and received IVT RG6179 at Week 0, 4 and 8, followed by post-treatment observation until Week 36.

 

Results:

Mean age was 62 years, 42% of patients were male, mean (range) baseline BCVA and CST were 64 (43-80) letters and 509 (271-893) µm, respectively. Mean (SE) BCVA change from baseline was +10.3 (2.6), +9.5 (2.1) and +8.4 (3.1) letters for the 0.25, 1 and 2.5 mg doses, respectively, with a combined mean of +9.3 (1.6) letters at 12 weeks. Mean CST change from baseline was -124 (44), -177 (59) and -184 (48) μm, respectively, with a combined mean of -161 (28) μm at 12 weeks. Of note, the BCVA and CST benefits were maintained during the post-treatment observation period. All doses of RG6179 were well tolerated across all 33 patients. Ocular AEs (n=27) were reported in the study eye of 16 of 33 patients. Of those AEs; 21 were mild, 5 were moderate, 1 was severe (worsening of uveitis; unrelated). Only 1 AE in 1 patient was reported as related to RG6179 (transient visual acuity loss). Two patients had a progression of pre-existing cataract; none developed new cataracts. There were no cases of treatment-related intraocular pressure increase, occlusive retinal vasculitis or systemic AEs.

 

Conclusions:

This phase 1 trial provides preliminary data on the safety and efficacy of the novel anti–IL-6 antibody RG6179 in patients with UME. Two phase 2 studies in DME (mono and combo) and two phase 3 trials in UME are currently underway to further assess the clinical potential of RG6179.

 

Presenter(s)

Presenting Author: Larissa Derzko-Dzulynsky

Additional Author(s):

Sumit Sharma MD; Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA., MD; Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Eric Suhler, Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Phoebe Lin, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Meike Pauly-Evers, PhD; F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland., F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

Daniela Willen, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

Robbie Peck, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

Federica Storti, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

Simone Rauhut, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

Tatiana Gott, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland

Benedicte Passemard, F. Hoffmann-La Roche AG, Basel, Basel-Stadt, Switzerland.

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