Having been outmanoeuvred first on price and then on dosing, Novartis is preparing its next line of defence in macular degeneration as sales of its flagship Lucentis plateau.
A phase II trial has shown that RTH258 is the equal of Eylea in preserving eyesight, a finding that supports the group’s decision to push the project into phase III late last year. After last year’s ex-US partnership on Fovista, Novartis is making clear that it does not intend to disappear from a market forecast to grow by more than 40% in the next five years.
RTH258 showed itself non-inferior to Bayer and Regeneron Pharmaceuticals’ Eylea in a 173-patient wet age-related macular degeneration (AMD) study, when measured by change in visual acuity after 12 weeks of treatment. In the trial, patients were injected with seven 6mg doses of RTH258 and eight 2mg doses of Eylea, with patients followed on secondary efficacy endpoints up to 56 weeks.
The Swiss group has already initiated its pivotal programme, a 1,000-patient head-to-head trial against Eylea that will measure visual acuity change at 48 weeks, with loading doses at baseline, four and eight weeks, followed by injections spaced as far apart as every three months. Eylea follows the same loading dose schedule but is typically dosed once every two months at the maintenance stage.
RTH258 came to Novartis from the private Swiss developer EsbaTech via Novartis's 2010 takeout of Alcon, bringing with it single-chain antibody fragment technologies that rely on active ingredients that are smaller and more durable than ranibizumab, the monoclonal antibody behind Lucentis.
Novartis holds ex-North American rights to Lucentis from its cross-town rival Roche. Sales of that agent have faltered since 2012, with greater acceptance of cheaper compounded Avastin as a substitute along with the launch of Eylea in late 2011. By 2020, worldwide sales of Lucentis will have sunk to $3.7bn from a peak of $4.3bn in 2014, with Novartis accounting for $2.1bn, according to EvaluatePharma’s consensus
Thus a rejuvenation of the Novartis AMD franchise was in order, especially as the group has committed so much to eyecare with the Alcon acquisition – Roche’s ophthalmological laboratories, by comparison, have in late development stages innovative products in the dry version of AMD and in optic neuromyelitis, but not wet AMD.
Fortunately for Novartis, Alcon had a promising project already in place in RTH258, but the business development side also got busy and struck an ex-US deal with Ophthotech on Fovista (Novartis pays up to shut out eye competition, May 20, 2014). That project blocks platelet-derived growth factor – rather than vascular endothelial growth factor as with Lucentis, Avastin, Eylea and RTH258 – and thus is viewed as complementary.
Having RTH258 gives Novartis a wholly-owned AMD asset that, assuming there are no interaction or mechanistic issues, could combine with Fovista globally. So far, Ophthotech, which retained US rights to the project, has put it into trials with Lucentis, Avastin and Eylea alike. Opthotech has claimed to be agnostic about which VEGF agent Fovista is combined with - however, Novartis is likely to have some opinions about this matter outside North America, and RTH258 must figure into this strategy.
So far, Bank of America-Merrill Lynch is willing to ascribe sales to the projects, pencilling in $360m in in-line Fovista sales for Novartis and $40m for RTH258 in 2020 – which would just about offset Lucentis’s losses over the same time.
With Fovista due to yield phase III data next year and RTH258 becoming more visible as it approaches a 2018 readout, look for those forecasts to move up, painting a picture of better health for the Novartis franchise.
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