Roche has reported midstage data with its double-headed antibody RG7716 in diabetic macular edema (DME) which suggests it could be a threat to current blockbuster VEGF drugs used for the disease.
The phase 2 BOULEVARD trial included a direct head-to-head comparison with Roche’s established VEGF inhibitor Lucentis (ranibizumab), which is partnered with Novartis, and showed that RG7716 was more effective than the older drug in improving visual acuity in DME patients.
The new drug combines both VEGF and angiopoietin-2 (ANG-2) inhibition and if approved would compete with Lucentis—which brought in $1.9 billion in ex-U.S. sales for Novartis last year and $1.5 billion for Roche in the U.S.—as well as Regeneron and Bayer’s fast-encroaching rival therapy Eylea (aflibercept).
Analysts at Jeffries said that Roche is in the midst of preparing for a phase 3 trial of RG7716 that, if positive, could pave the way for a launch in 2022. They estimate around a third of Eylea’s $3.7 billion 2017 sales came from DME.
BOULEVARD compared two doses of RG7716 (1.5mg and 6mg) to Lucentis 0.3mg, with all three regimens given by injection into the eye once a month, to 229 previously-untreated patients with DME. Data from 169 patients were reported over the weekend at the Angiogenesis, Exudation, and Degeneration 2018 conference in Miami.
After 24 weeks, patients on the higher dose of Roche’s new drug had a 13.9-letter improvement on Best Corrected Visual Acuity (BCVA) testing, compared to 11.7 letters for the lower dose group and 10.3 letters for Lucentis.
The difference between high-dose RG7716 and Lucentis was statistically significant, according to Roche, which said that result was backed up by data on the proportion of patients who achieved a two- or three-line improvement on sight charts—70.5% and 43.2% for high-dose RG7719 compared to 57.1% and 32.7% for Lucentis.
Those visual improvements were also accompanied by assessments of the severity of retinopathy—the degeneration of cells in the retina—which also favored the bispecific antibody.
Jefferies said the data seem to suggest RG7716 is superior to Lucentis, although they caution that with the higher dose now looking the most likely to be taken forward in development “there is some scrutiny on safety given the 6mg dose is equivalent to 2mg of Lucentis [and] we know there are increased cardiovascular events at higher doses of Lucentis in DME.” There was however no evidence of greater cardiovascular risk for RG7716 in this study, they pointed out.
Roche chief medical officer Sandra Horning, M.D., said this is the first time that a drug targeting both VEGF and ANG-2 has shown clinical activity in a trial. “There remains a significant unmet medical need for more efficacious and longer-lasting therapies for DME,” she added.
Last year, Regeneron scrapped an Eylea follow-up combining aflibercept with ANG-2 antibody nesvacumab after disappointing phase 2 results, while Novartis is also working on a new longer-acting VEGF inhibitor called brolucizumab that matched Eylea in a head-to-head trial.