Until now, Regeneron’s big advantage over Novartis and Roche in the ophthalmology wars was the price difference between Eylea and Lucentis, driven by less frequent dosing in the primary indication of age-related macular degeneration. Now it looks like Regeneron has stolen a march in a second condition by showng superiority in a head-to-head trial in diabetic eye disease.
The US National Institutes of Health has reported topline data from the Protocol-T trial in diabetic macular oedema showing that patients taking Eylea had significantly clearer vision than those taking Lucentis or off-label Avastin after a year's treatment. The agent is the sole reason Regeneron is a profit-making company, and a potential superiority claim on its label holds with it the promise of generating extra sales.
This is how investors viewed the data. Regeneron shares rose 8% Friday to a record high of $369.64 following the announcement. As it is an investigator-led trial by the NIH-backed Diabetic Retinopathy Clinical Research Network, the Tarrytown, New York-based group said it had no data beyond the topline results supplied to the study investigators. Further details are to be published in a peer-reviewed journal and disclosed at an upcoming medical meeting, Regeneron said.
Short on detail
The Protocol-T trial is a three-arm test in 660 patients comparing the US-approved oedema doses of Eylea, Lucentis and Avastin on efficacy and safety. All three are agents targeting vascular endothelial growth factor, which aids in the growth of new blood vessels; diabetic macular oedema and other degenerative retinal conditions result from the leakage of fluid from the blood vessels. Lucentis and Avastin are antibodies, while Eylea is a kinase inhibitor.
Regeneron’s press release stated that treatment with Eylea resulted in a significantly greater improvement in mean change in best-corrected visual acuity from the beginning of the trial to 52 weeks over the two competing agents. The number of ocular and systemic safety adverse events was similar for all three drugs; on cardiovascular safety endpoints, 2% of Eylea patients suffered a non-fatal myocardial infarction or stroke, or vascular death, versus 4% of Avastin patients and 5% of Lucentis patients.
This was the best news for Regeneron in what was clearly a good news, bad news day. Amgen sued it and partner Sanofi over the intellectual property of the heart project alirocumab, while the Sanofi-Regeneron antibody partnership also initiated phase III work in atopic dermatitis for dupilumab.
First not necessarily best
Lucentis has long been criticised for being an expensive drug, and in eye disease the compounded version of Avastin, the Roche cancer antibody, has been substituted off-label at a much lower price. Lucentis comprises a fragment of Avastin's active ingredient targeted more specifically to the tissues of the eye.
Meanwhile, Eylea’s advantage from the beginning has been a longer interval between doses, which allowed it to compete both on price and convenience; in the first indication of age-related macular degeneration (AMD), Eylea costs $14,700 per patient versus Lucentis’s $25,800, according to data from EvaluatePharma’s US sales, volume and price module.
In response to the criticism, Roche, which holds US rights, dropped the Lucentis dose from the 0.5mg monthly in AMD to 0.3mg monthly in oedema, cutting the annual per-patient price to $15,500, although Novartis retained the 0.5mg dose in ex-US territories. Roche’s decision made Lucentis competitive with Eylea – its oedema dosing protocol is very similar to AMD, with the exception of more injections when beginning therapy.
And along with the pricing decision, Roche also had a clear first-mover advantage in diabetic macular oedema, having earned approval in 2012. Eylea earned an OK earlier this month from the FDA, and in August in the European Union, where Bayer markets the drug.
Thus the results of Protocol-T will give Regeneron a fightback strategy – the potential to add a superiority claim to Eylea's label, not to mention the possibility that its sales force will be able to point to a safety advantage.
Roche and Novartis have been fighting an uphill battle to prove the worth of Lucentis over competitors, something reflected in analyst forecasts showing that sales of the agent will essentially plateau until patent expiry at the end of this decade. Full data from Protocol-T will probably do nothing to change this outlook.