ESC - Elinogrel Shows Its Stuff but Brilinta Still the Star

August 31, 2010 ESC - Elinogrel shows its stuff but Brilinta still the star

Jonathan Gardner

The platelet aggregation inhibitor elinogrel has passed its midterm exam with high scores, but still has some studying to do to catch up with the class’ star student, Brilinta. Data from a phase II trial in patients undergoing percutaneous coronary interventions look to be sufficient to advance the Portola Pharmaceuticals drug, licensed to Novartis, into phase III trials, but with a forecast launch date of 2013 the anticoagulant may end up trailing the AstraZeneca candidate by three years.

Based on the results of the Innovate-PCI trial, Portola said it expects Novartis to begin a programme for the P2Y12 ADP receptor antagonist in the first quarter of 2011. It is likely that the programme will test elinogrel’s ability to avert major cardiovascular events in patients with acute coronary syndrome, Brilinta’s targeted population, along with chronic coronary heart disease. With Brilinta’s PDUFA date rapidly approaching, however, the Astra drug would have first-mover advantage in the ACS population, meaning elinogrel may need to generate stronger safety or efficacy data to support its commercial prospects.

The handover

The Innovate-PCI trial compared elinogrel, also known as PRT128, to Plavix in 650 patients scheduled to undergo a non-urgent PCI. The dose-ranging trial found more rapid and effective anti-platelet activity in the elinogrel patients than the Plavix patients without an increase in major or minor bleeding incidents, although the four-arm study was not powered to test a specific primary endpoint.

Presented at the European Society of Cardiology meeting in Stockholm, the trial will form the basis for Novartis’ phase III registration trials. Under the terms of the 2009 deal to secure worldwide commercialisation rights for elinogrel, Novartis now takes full control of the research programme after sharing costs with Portola in phase II. Novartis has not made a formal announcement of its plan for the pivotal programme.

Under the terms of the licensing deal, which saw Novartis pay the California firm $75m upfront with up to $500m in milestones, Portola does have an option to co-fund the phase III programme and co-promote in the US in hospitals and certain specialty markets. The company has made no signal on whether it will exercise that option, although with thousands of patients likely to be enrolled in the phase III programme – Brilinta’s Plato study enrolled more than 18,000 worldwide – co-funding may be beyond the means of a privately funded company that has another blood-thinner in phase II as well as a cancer drug in phase I.

Changing market

Elinogrel completes its phase II test at a time of change for the anti-coagulant market (Therapeuticfocus - Anti- thrombotics face a period of change, July 26, 2010). Plavix loses patent protection in 2011 and Lovenox, in a surprising development, also is subject to competition as Novartis’ Sandoz division has been successful in achieving FDA approval of a bio-generic copy (What a moment for Momenta, July 26, 2010).

As such, Brilinta and elinogrel will need to demonstrate some competitive advantage to be embraced by insurers. Both have some advantage over Plavix in that they are reversible, meaning that patients taking them would not have to wait five days before undergoing surgery, as Plavix patients do, because of the risk of bleeding.

Brilinta is closing in on a key FDA decision, although questions hang over inconsistencies in its pivotal trials, raising the possibility it could be forced to repeat some studies (Brilinta gets yes from adcom but what will FDA say?, July 29, 2010).

Brilinta setting the pace

Should Brilinta make it to market first, its advantage is clear: EvaluatePharma’sconsensus estimates for 2016 have it selling $2bn worldwide, compared with just $167m for elinogrel, which would have been on the market just three years should analyst projections for a launch in 2013 come to pass. Still, the elinogrel consensus masks some wide variations in analyst projections. The most optimistic is Nomura, which suggests a $2bn peak in 2021, double that of JP Morgan, which projects a peak of $983m in 2020 with sales of $518m in 2016. Cowen, meanwhile, forecasts just $100m in 2015.

Whatever the case, there remains some scepticism that elinogrel will be able to match Brilinta. Clear superiority on safety or efficacy in phase III, or an adverse regulatory decision for Brilinta, could help elinogrel.