AstraZeneca Says $3.5bn Brilinta Sales Forecast By 2023 Now Unattainable
Executive Summary
AstraZeneca will cut its sales forecasts for Brilinta after the therapy failed to beat the older blood thinner clopidogrel in the comparison EUCLID study in peripheral artery disease.
AstraZeneca and investors are reassessing peak sales prospects for the UK drug maker's 's blood thinner Brilinta (ticagrelor) after it failed to help patients with serious circulatory problems in their legs.
The setback came with news Oct. 4 that Brilinta – which AstraZeneca had previously said could generate peak revenue of $3.5bn by 2023 – did not show a benefit compared with the older, generic blood thinner clopidogrel in treating peripheral artery disease (PAD) in its large-scale EUCLID clinical trial. PAD usually affects the legs.
The outcome is a big disappointment to AstraZeneca’s and follows its failure in March to expand Brilinta's label into stroke after the therapy failed to beat aspirin in a large-scale study, SOCRATES, in preventing major vascular events in patients with acute ischemic stroke or transient ischemic attack. (Also see "Brilinta No Better Than Aspirin In Stroke Trial" - Scrip, 24 Mar, 2016.) Brilinta is already approved for the treatment of acute coronary syndrome.
Brilinta is the third best seller in AstraZeneca's cardiovascular & metabolic disease unit after top-placed statin Crestor (rosuvastatin) and DPP-4 inhibitor Onglyza (saxagliptin), respectively, and is one of the half-dozen growth prospects that AstraZeneca is counting on to fuel sales in order to return to growth in 2017 after the loss this year of patent protection for Crestor in the US – a challenge that follows the patent expiry in 2015 of proton-pump inhibitor Nexium (esomeprazole) - while the loss of patent protection still awaits antipsychotic Seroquel XR (quetiapine extended release) in 2017.
But the goal of generating $3.5 billion in Brilinta sales by 2023, set two years ago by AstraZeneca during its takeover battle with Pfizer Inc., is now probably out of reach now, the company acknowledged Oct. 4 after announcing the EUCLID trial setback. But it stressed the drug has strong upside in existing indications.
"The $3.5bn target is no longer attainable given EUCLID - but Brilinta's upside in existing indications of acute coronary syndrome and myocardial infarction are still significant and will play an important part in our return to growth." - AstraZeneca spokesperson
"Yes, the $3.5bn target is no longer attainable given EUCLID - but Brilinta's upside in existing indications of acute coronary syndrome and myocardial infarction are still significant and will play an important part in our return to growth," a spokesperson for the company said. It added that even if EUCLID had been successful in PAD the indication wouldn't have contributed to sales before 2018. "Current Brilinta indications remain the drug's driving force for near term," they added.
Brilinta is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs) and works by inhibiting platelet activation. It has been shown to reduce the rate of atherothrombotic CV events, such as heart attack or CV death, in patients with acute coronary syndrome (ACS). Launched in 2011, annual sales by Brilinta have risen steadily from $21m that year to $476m in 2014 and $619m in 2015.
The EUCLID study investigated whether treatment with ticagrelor versus clopidogrel - formerly the branded product Plavix from Sanofi and Bristol-Myers Squibb Co. - and given as antiplatelet monotherapy would reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.
The trial, the largest cardiovascular outcomes trial to date conducted exclusively in symptomatic patients with PAD, involved 13,885 patients in 28 countries. It evaluated the treatment of Brilinta 90 milligram tablets twice daily versus clopidogrel at 75 milligrams once daily for the prevention of atherothrombotic events - a composite of cardiovascular death, heart attack or ischemic stroke. The primary endpoint of the trial was the time to first occurrence of any such event.
Beating clopidogrel would not only have put Brilinta on track for approval in a new setting, but it could also help it compete against the cheaper generic.
The EUCLID trial is part of PARTHENON, a huge cardiovascular (CV) outcomes program, involving nearly 80,000 patients at high risk of CV events due to underlying disease. It includes a number of studies covering broad patient populations and a wide range of CV disorders, including coronary artery disease (PEGASUS-TIMI 54), acute ischemic stroke or transient ischemic attack (SOCRATES) and patients with type 2 diabetes at high risk of CV events (THEMIS). Full results from EUCLID will be presented next month at the American Heart Association Scientific Sessions in New Orleans, Louisiana.
Unfortunately for AstraZeneca, the latest trial results represent the second major failure of the PARTHENON program, those being SOCRATES and EUCLID. Top-line results of the THEMIS trial are to be expected in 2018 and will be the final major readout for Brilinta in the PARTHENON program, Datamonitor Healthcare analyst John Allen said.
He noted that Brilinta was able to attain some off-label use in ischemic stroke prior to its failure in the SOCRATES trial. "It will be interesting to see if physicians continue to use the medication off-label after this failure. My inclination is that use of the medication will be reduced based on the poor clinical trial results as the medication is significantly more expensive than aspirin (the comparator) and being that the trial shows that the potential benefit of Brilinta is very limited. I would be inclined to believe physicians would transition back to aspirin," Allen said.
Analysts at JPMorgan in a reaction note Oct. 4 said peak sales forecasts for Brilinta had been revised lower after the negative SOCRATES trial results in March, and that the spotlight would now be on the final Phase III THEMIS CV outcomes study for Brilinta in 2018, in patients with type 2 diabetes and coronary artery disease without a previous history of heart attack or stroke.
"Following today¹s negative newsflow, we believe that expectations for a positive outcome in THEMIS are likely to be low," they added.