Novartis might be feeling the strain of its Alcon eyecare division, but in terms of pipeline developments one of the unit’s key projects, brolucizumab, looks to have delivered positive data in its first two pivotal studies.
That said, all brolucizumab has demonstrated is, again, that it is no worse than Regeneron’s blockbuster Eylea, and with questions outstanding over its potential label sellside consensus forecasts have come off considerably. It looks unlikely that brolucizumab can save Novartis’s already declining Lucentis franchise.
Lucentis and brolucizumab are both antibody fragments against VEGF, a protein that induces angiogenesis and is thought to be implicated in the progression of wet age-related macular degeneration (AMD), and at one point the latter was seen as a possible follow-on to the former. Eylea, meanwhile, is a VEGF-trapping fusion protein.
The two pivotal wet AMD trials that read out today, Hawk and Harrier, had a similar design, and both have shown brolucizumab to be non-inferior to Eylea on the primary efficacy measure of change in best corrected visual acuity from baseline at week 48; all doses have met significance, Novartis said.
Thus the group’s argument comes down to minutiae, specifically the possible advantage that reduced dosing – every 12 weeks – might give brolucizumab versus Eylea.
While full data are being kept back for presentation at a scientific meeting, Novartis said Hawk and Harrier showed 57% and 52% of patients respectively being maintained exclusively on 12-weekly dosing. This compares favourably with the roughly 30% of wet AMD patients that Eylea is able to manage on 12-weekly dosing.
However, some analysts had expected brolucizumab to do better: Bernstein, for instance, was hoping for 60% or above. Novartis had spelled out its game plan earlier, saying that if 12-weekly brolucizumab dosing failed to maintain at least 40% of patients the project would not be taken to registration.
Another possible advantage for Novartis includes lower cost of goods for brolucizumab versus Eylea – it has already said it wants to compete on price. However, the Swiss group says it will not file brolucizumab until next year while it runs a pharmacokinetic trial and works on a low-cost manufacturing process.
And it is far from certain whether data so far are strong enough to allow 12-weekly dosing to be a specific label claim for brolucizumab, though presumably if the product is approved Novartis can stress dosing advantages in marketing materials.
Novartis gained the asset through its 2010 takeover of Alcon, the eyecare division whose underperformance has prompted an internal review of “all options”. Many are now expecting the unit to be spun out, though it is not clear how much needs to be invested in it to get it to a point where a decent exit price can be achieved.
A final note of caution is that the sellside in general has been growing increasingly disenchanted with brolucizumab, whose consensus 2022 revenue forecasts have shrunk from $573m a year ago to $201m at present, according to EvaluatePharma. Novartis’s Lucentis franchise has been hit not only by Eylea but also by off-label use of Avastin.
Today Bernstein wrote that 12-weekly dosing giving maintenance in 52-57% of patients was “good enough” for brolucizumab. Unfortunately for Novartis, this sounds awfully like damning the asset with faint praise.
|Pivotal trials of Novartis's brolucizumab|
|Study||Study detail||Note||Trial ID|
|Hawk||1,600 subjects, 3mg & 6mg, non-inferiority vs Eylea||57% maintained exclusively on 12-week dosing||NCT02307682|
|Harrier||1,200 subjects, 6mg, non-inferiority vs Eylea||52% maintained exclusively on 12-week dosing||NCT02434328|