ESC: All eyes on Pfizer’s tafamidis as European heart confab kicks off

When Pfizer reported unexpectedly strong top-line results from its phase 3 study of tafamidis in transthyretin cardiomyopathy (TTR-CM) in March, it set the stage for a potential showdown with Alnylam and Ionis, both of which are gunning for the same market. So it’s no wonder that investors are eagerly awaiting the full data from that trial, called ATTR-ACT, which will be presented Monday at the European Society of Cardiology (ESC) meeting in Munich.

In patients with transthyretin cardiomyopathy, which is a form of the rare disease transthyretin amyloidosis (ATTR), Pfizer’s drug reduced all-cause mortality and cardiovascular-related hospitalizations by a statistically significant amount over placebo, leading analysts at the time to estimate it could be a $1 billion-a-year blockbuster. Now Pfizer is expected to detail those results, spelling out exactly how big the reduction in adverse heart events was in the trial—particularly the risk of mortality.

Although the Pfizer data will likely steal the spotlight at ESC, plenty of other pharma companies are hoping to make a splash. They include Johnson & Johnson, Bayer and AstraZeneca—all of which are presenting data aimed at boosting the market for their blood thinners—and Amgen, which hopes to make an impact with new outcomes data on its PCSK9 cholesterol-lowering drug Repatha.

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Even though Pfizer’s tafamidis will initially address a rare disease, it’s a significant opportunity because the drug could be the first therapy to actually change outcomes, depending, of course, on the ATTR-ACT data, analysts have said. They’re hoping Pfizer will break out the reduction in all-cause mortality from the frequency of hospitalizations, for example, which will help clinicians understand the true benefits of the drug. 

In a note sent to investors earlier this week, Credit Suisse analysts predicted Pfizer’s presentation at ESC would be “game changing.” They spoke to cardiologists, who said they would be pleased to see a 10-15% reduction in all-cause mortality and heart-related hospitalizations in the trial, Credit Suisse noted. But investors are likely to be much more demanding. “Interestingly, investor expectations for the data seem to be much higher than what is clinically meaningful, and we believe that anything short of a 20-25% improvement in the composite primary endpoint could disappoint investors,” the analysts wrote.

A spokeswoman for Pfizer declined to provide details to FiercePharma in advance of the ESC presentations, but she did say the company expects the results will help it to develop a market for tafamidis in TTR-CM, which is largely underdiagnosed. “The data analysis will help identify the patients” most likely to benefit from the drug, she said.

The long-term benefits of antiplatelet therapy will also be a big topic at ESC. J&J and Bayer are planning data presentations on their drug Xarelto, including results from a trial looking at the mortality benefit in patients with heart failure and coronary artery disease. Sales of Xarelto have been up and down, so if the trial shows a reduction in all-cause mortality, it could be a major boost for the companies: Credit Suisse reports it will hike its forecast of Xarelto peak sales by $750 million if the trial succeeds. Spokespeople for J&J and Bayer declined to comment prior to the release of the data at ESC.

AstraZeneca is planning several presentations of outcomes data from its trials of Brilinta, another blood thinner that has been underperforming Street estimates of late. Last year, the company used ESC as a stage for data showing the drug cuts the risk of cardiovascular death by 29% over placebo in patients who take it within two years of suffering a heart attack, or within one year of taking an anticlotting drug.

Now the company is adding data from three studies, including one investigating outcomes in patients who have other risk factors, like renal disease or diabetes, and who take Brilinta after percutaneous coronary interventions. Ludovic Helfgott, global vice president of cardiovascular, renal and metabolism at AstraZeneca, said in an interview with FiercePharma that he hopes the data will help persuade physicians who are reluctant to prescribe the drug to take a more serious look at it.

“Brilinta has been present in the guidelines across the world, both in the first year after the acute event and then afterwards, for the past two years. But what we need to see is that guidelines are actually applied in real life,” Helfgott said. “We believe this data will help physicians understand the need for prevention and long-term treatment.”

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ESC will also provide a forum for AstraZeneca to talk up Lokelma, its new drug to treat hyperkalemia. AstraZeneca suffered multiple FDA and EMA rejections over manufacturing issues before finally winning approval for the drug earlier this year. AstraZeneca acquired the Lokelma in a $2.7 billion buyout of ZS Pharma, and nabbed the approval based on data showing it reduces abnormally high potassium in the blood in an hour and restores it to normal levels in about two hours.

Hyperkalemia can be fatal, and there are few treatment options, so analysts are still hoping the drug will reach blockbuster status, despite the regulatory delays. AstraZeneca will present data from two trials of Lokelma in heart-failure patients at ESC, including one that examines the link between dosing level and the risk of mortality. Helfgott said he hopes the study results will help AstraZeneca build the market for the new drug.

The benefits of lowering cholesterol levels with PCSK9 inhibitors has been a major topic of interest in past years at ESC, and this year will likely continue that trend, thanks to Amgen, which will be presenting data from six trials of its drug Repatha. They include two analyses of the company’s highly watched Fourier trial that focus on the drug’s efficacy in people with metabolic syndrome and established heart disease.

RELATED: Citing appeals court 'anarchy,' Amgen asks SCOTUS to weigh its PCSK9 patent spat with Sanofi

But Amgen also hopes to draw attention to new numbers it’s presenting to address ongoing cost-effectiveness concerns. Repatha and its market rival, Sanofi and Regeneron’s Praluent, were initially priced around $14,000, prompting insurers to put up barriers to prescriptions and stunting their launches.

Last summer, Amgen released data concluding that Repatha is cost effective at a price of $13,225 in patients with super-high LDL that can’t be controlled with statins. At the time, the company said the study confirmed the benefits of prescribing Repatha to the highest-risk patients. Sales of the drug more than doubled to $225 million last year. But Repatha has a long way to go to reach the blockbuster status analysts once expected.

At ESC this year, Amgen will present data on productivity loss and indirect costs associated with cardiovascular events in Europe. Andrew Hamer, global development medical director for cardiovascular at Amgen, told FiercePharma he hopes the results will send a message to healthcare systems about the importance of preventing major cardiac events by lowering cholesterol in patients facing a high risk of heart attack and other coronary events.

“I think everybody is aware of the productivity loss that comes after strokes, but acute coronary syndrome seems to have a similar level of productivity loss," Hamer said. "That’s not been quite as well realized in Europe or around the world. We need to make sure that when countries’ health care systems look at treatments, that they take into account all of the costs of the illnesses that we’re trying to prevent.”