Roche goes for death or glory with faricimab

Roche is stepping up the defence of its eye franchise, but the real test will come with pivotal readouts for its new contender versus Regeneron’s Eylea.

Roche has long talked up the potential of its new eye disease candidate, the anti-VEGF/Ang2 bispecific antibody faricimab. Mid-stage data in wet age-related macular degeneration suggest that the project might be just as effective as the group’s ageing blockbuster Lucentis, but with less frequent dosing.

This is not to be sniffed at as Lucentis requires monthly injections into the eye, limiting patient compliance. But, to really make waves, Roche needs to show that faricimab has an edge over the dominant player, Regeneron and Bayer’s Eylea – and this question could be answered by two recently started head-to-head phase III trials in another indication, diabetic macular oedema.

Roche is taking a big gamble with the phase III Rhine and Yosemite studies, at 900 patients apiece. Going directly against Eylea was a move that the Swiss group probably had to make to give faricimab, previously known as RG7716, a chance of competing. It drew criticism earlier this year for only including a Lucentis comparator in the phase II Boulevard study in diabetic macular oedema (Roche eyes diabetes success where Regeneron failed, 13 February 2018).

The Swiss company appears to have taken this feedback on board with the Rhine and Yosemite trials, but it will be a while until it becomes clear whether the bet has paid off, with the studies set to complete in 2021.

Stairway

In the meantime, Roche is looking at other uses for faricimab. The phase II Stairway trial, presented at the American Academy of Ophthalmology meeting in Chicago over the weekend, tested the project in wet AMD, specifically looking at longer-term dosing.

The study found similar outcomes on best-corrected visual acuity (BCVA) with faricimab dosed every 12 or 16 weeks, or monthly injections of Lucentis.

Stairway was positive, but Roche appears to be keeping quiet about the outcome of another study of faricimab in AMD, called Avenue. Roche has previously said the trial is in "follow up", but at the time of publication had not responded to a query about when data might be available.

A 12 or 16-week dosing schedule for faricimab will probably not count for much unless Roche can show improved efficacy versus Eylea – particularly as Regeneron’s drug recently got the US FDA go-ahead for 12-week dosing.

Roche plans to start phase III trials of faricimab in AMD next year, and it will be interesting to see if it is compelled to pit its project against Eylea again.

Stronger or longer? Roche's ophthalmology trials
Indication Study Details Trial ID Primary completion
Faricimab (RG7716) 
Diabetic macular oedema Rhine (phIII) Every 8 wks vs Eylea NCT03622593 Sep 2021
Diabetic macular oedema Yosemite (phIII) Every 8 wks vs Eylea NCT03622580 Sep 2021
Wet AMD Stairway (phII) Every 12/16 wks vs Lucentis NCT03038880 Reported
Wet AMD Avenue (phII) Every 4-8 wks vs Lucentis NCT02484690 Sep 2017
Port Delivery System (RG3645)
Wet AMD Archway (phIII) Vs monthly Lucentis NCT03677934 Feb 2021
Wet AMD Ladder (phII) Vs Lucentis NCT02510794 Reported
Source: EvaluatePharma, Clinicaltrials.gov.

Should faricimab fall short, Roche has another trick up its sleeve to prolong the life of its ophthalmology franchise.

It has been investigating the use of an intravitreal implant, obtained when it bought Forsight Vision4 in January 2017, which is filled with  ranibizumab, the active ingredient of Lucentis, and surgically implanted in the eyeball. The Port Delivery System (PDS) leaches the drug into the eye on a constant basis and is refilled periodically; the refilling is another needle-in-the-eye situation but the intention is that this procedure will be rarer than standard Lucentis administration and thus more tolerable.

Data from the phase II Ladder study released in the summer suggested that 80% of patients on the highest dose of the drug, 100mg/ml, were able to go six months or more between refills of the PDS. These patients had similar visual outcomes to the control group, which was treated with 0.5mg of Lucentis injected once a month.

Roche is continuing its research, and last month began the pivotal phase III Archway trial, testing the PDS with a 100mg/ml ranibizumab dose refilled every six months. This is due to report in mid-2022 and will show whether the implant is as safe and effective as the injected version.

The other important point for its commercial prospects is whether the port system is any less unpleasant for patients, and if they would take an implant and at least two ocular jabs per year over the current regimens, particularly as less frequent alternatives become available. 

Other contenders could also soon be in the frame, including Novartis's brolucizumab, which has shown noninferiority to Eylea and is set to be filed in December. Allergan/Molecular Partners' abicipar is due for submission in 2019, though worries about intra-ocular inflammation raise questions about this project's commercial potential (Allergan’s eye contender cannot knock Eylea off its perch, 20 July 2018). 

Roche will need more than the latest data to give Eylea a run for its money, but at least it is taking the fight to its rival. The next few years should show whether the Swiss group’s decision was brave or foolhardy.

This story has been updated to reflect the fact that the Port Delivery System is filled with ranibizumab, not Lucentis.

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