ESC 2018 preview – Getting to the heart of Pfizer’s amyloidosis data

The most eagerly awaited data from this year’s European Society of Cardiology congress will involve Pfizer’s tafamidis, which has already scored a win in the Attr-act trial in cardiac amyloidosis. The questions now are around the size of the drug’s benefit and how much it might hurt Alnylam and Ionis.

Meanwhile, results from the investigator-sponsored Ascend study could give an indication of whether Amarin’s fish oil supplement Vascepa will succeed in its huge cardiovascular outcomes trial. And Johnson & Johnson and Bayer are continuing their label-extension plans for their blood thinner Xarelto, with two studies set to report at ESC.

Pfizer’s surprise success with tafamidis, toplined in March, heralded a new entrant in the amyloidosis race, which until then had been dominated by Alnylam and Ionis (Therapy focus – Pfizer blows hereditary amyloidosis fight open, April 4, 2018).

Tafamidis’s win in the Attr-act trial came in the cardiac subtype of amyloidosis, boding ill for Alnylam’s newly FDA-approved RNAi therapeutic, Onpattro.

Onpattro got the go-ahead in polyneuropathy caused by hereditary transthyretin-mediated amyloidosis earlier this month; Alnylam had hoped for a broader indication also covering cardiomyopathy, or at least the inclusion of cardiac data on its label, but the FDA obviously had other ideas.

Similarly, Ionis’s Tegsedi was approved in July in Europe for polyneuropathy, and a US decision is expected by October 6. Interestingly, tafamidis was knocked back by the FDA in polyneuropathy in 2012, but it is marketed in this indication in Europe as Vyndaqel.

So far, all that has been disclosed is that the Attr-act trial met its primary endpoint, a composite of all-cause mortality and cardiovascular-related hospitalisation at 30 months. One big question is whether there was a dose response: Attr-act tested doses of 20mg – the dose approved in Europe – and 80mg.

Another outstanding issue, according to Stifel analysts, is whether the benefit was driven by patients with idiopathic, rather than hereditary, amyloidosis; the former made up around 70% of the Attr-act trial population.

Evercore ISI’s Umer Raffat said that if tafamidis showed a benefit of 25% on the primary outcome it would have exceeded expectations, but he concluded: "We need to see a clear benefit on mortality."

Fish oil or snake oil? 

Sunday will see two separate presentations of data from the Ascend trial, which, though not testing Amarin’s fish oil formulation Vascepa, could nevertheless give insight into Vascepa’s approvability.

The first presentation concerns data from the aspirin arm of the study, but the second looks at the ability of the fish oil supplement Lovaza to prevent cardiovascular events in diabetic patients.

The primary outcome of Ascend is the rate of a combination of non-fatal heart attack, non-fatal stroke or transient ischaemic attack, or vascular death, excluding confirmed cerebral haemorrhage. It is doubtful that Lovaza will produce a definitive benefit, but if it does the fortunes of fish oil developers could be revolutionised. The win would likely be interpreted as a harbinger of success in Vascepa’s huge cardiovascular outcomes trial, Reduce-It (Sink or swim for fish oils, and Amarin, July 16, 2018).

Bleeding love

Johnson & Johnson and Bayer are expecting data from two trials of Xarelto: Mariner, evaluating venous thromboembolism in previously hospitalised patients, and Commander HF, looking at major cardiovascular events in heart failure patients.

Xarelto has been a huge seller, but the companies have been trying to expand its uses as competition from Bristol-Myers Squibb/Pfizer’s Eliquis ramps up (Spotlight – Xarelto and Eliquis's blood feud, 12 September 2017).

Some of these label-expansion efforts have gone well, such as the Compass trial in coronary and peripheral artery disease, presented at last year’s ESC. But Navigate Esus, in secondary stroke prevention, was stopped for futility in October. It will soon become clear which category Mariner and Commander HF fit into.

Also featuring at ESC will be data with another blood thinner, Astrazeneca’s Brilinta, from a 16,000-patient investigator-sponsored trial, Global Leaders, looking at a combination of the drug with aspirin.

Meanwhile, full results from the Camellia-Timi cardiovascular outcomes trial of Eisai and Arena’s obesity drug Belviq are unlikely to improve its commercial prospects, as the companies have already said that this showed non-inferiority, but not superiority, to placebo.

Follow Madeleine Armstrong and Elizabeth Cairns on @ByMadeleineA and @LizVantage for live tweets from the ESC conference, which is taking place in Munich on August 25-29.

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