- Roche AG's novel treatment for eye disease outperformed blockbuster drug Lucentis in a Phase 2 study, prompting the company to set its sights on late-stage development.
- The BOULEVARD study evaluated whether Roche's candidate, called RG7716, was better than Lucentis at improving visual acuity in patients with diabetic macular edema (DME). Data showed patients on a 6 mg regimen of the investigational drug could see 13.9 more letters on an eye chart after 24 weeks of treatment, versus 10.3 letters for patients receiving 0.3 mg of Lucentis.
- Roche is also assessing RG7716 as a treatment for neovascular age-related macular degeneration (nAMD) in two other mid-stage trials, AVENUE and STAIRWAY. Following more data analysis, the Swiss pharma intends to meet with regulators to discuss the drug's Phase 3 program.
Regeneron Pharmaceuticals Inc.'s Eylea (aflibercept) has proven a formidable threat to Roche since first gaining approval in 2011. Like Roche's Lucentis, it carries DME and nAMD indications, yet has been able to wrestle away a sizeable chunk of those market shares. Regeneron reported Eylea sales of $953 million during the third quarter, a 12% increase year over year that, importantly, materialized even as Roche made advances with Lucentis.
"Roche had a strong Lucentis quarter based on new launch into DME, so we weren't sure if that would take share from Eylea or not," Evercore ISI analyst Josh Schimmer wrote in a Nov. 8 note. "But looks like U.S. Eylea performed well, with no major inventory shift."
With Roche's blockbuster just two years from losing patent exclusivity in the U.S., the big pharma is looking for follow-on products. So far, the best bet seems to be RG7716, a novel bispecific that inhibits vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). In addition to the 6 mg dose, BOULEVARD tested a 1.5 mg dose and found patients who received it had average visual acuity gains of 11.7 letters.
RG7716's victory over Lucentis appears to be an early step in a long journey, however.
"So far at least, Roche has shown that their combination product, when given at a materially higher dose, does better than Lucentis alone, which is more or less consistent with the prior observations about Eylea," wrote Leerink analyst Geoffrey Porges in a Feb. 12 note on Regeneron. "The lack of effective control for anti-VEGF exposure in their trials suggests to us a more complicated phase III design, longer timing and lower odds of success, than investors now discount into REGN's stock price."
Porges also detailed how, at the Bascom Palmer Angiogenesis meeting in Miami where Roche unveiled its latest data, attendees weren't sold on the potential for either Novartis AG's investigational eye therapy brolucizumab nor RG7716 — at least when it came to outdoing Eylea.
"At best, we believe the signal for RG7716 is modest, and with the variability in these results, the conflicting signals from the trials and the unreliability of such small difference, this effect could easily disappear in phase 3," Porges wrote. "Even if RG7716 succeeds at showing superiority to Lucentis, and confirming the signal from this trial in larger studies, it then looks, as one attendee at the meeting suggested, 'just like Eylea.'"
Leerink maintains an "Outperform" rating for Regeneron, with a stock price target of $502 per share. Regeneron stock opened at $339.68 per share on Monday, up 1% from Friday's close. Roche shares, which trade on the Swiss stock exchange, were up 1.5% to CHF 219.15 (about $233.51) apiece.
Roche will hold a conference call on Feb. 13 to discuss the BOULEVARD results.
"For the first time in diabetic macular edema, a clinically meaningful and statistically significant improvement in visual acuity compared to anti-VEGF alone has been demonstrated by simultaneously neutralising both angiopoietin-2 and VEGF-A with a bispecific antibody," Sandra Horning, Roche's chief medical officer, said in a Feb. 12 statement.