Anthera shares fall on failure of heart drug

It was always the riskier of Anthera Pharmaceuticals’ two lead drugs, so news that a trial of varespladib, a novel first-in-class treatment for acute coronary syndrome (ACS), had been stopped due to a lack efficacy might have produced a more sanguine reaction from the market.

Instead Anthera’s shares plunged by 47% to $3.38 in early trade today. Many in the market clearly had hopes of a double trial win for the company following last week's decision by the regulator to let a phase II study of lupus drug blisibimod continue after an interim look at the data. Those hopes have now been dashed, meaning much rests on the final read out from the blisibimod trial, due at the end of the second quarter.

Novel approach

Varespladib was always going to be a long bet for a number of reasons (Event – Anthera looking at a year of catalysts, February 23, 2012) - chiefly because the drug is currently the only sPLA2 inhibitor in clinical development, meaning there is no precedent to benchmark its likely success or failure, or help determine whether the Vista-16 trial was correctly designed.

The drug, originally discovered by Eli Lilly, was developed on the premise that phospholipase A2 enzymes break down phospholipids, releasing fatty acids and lysophospholipids. These fatty acids are thought to have an inflammatory effect, contributing to atherosclerosis or the hardening of the arteries that can cause coronary events. So inhibiting PLA2 should prevent atherosclerosis.

Along with the novelty of the mechanism of action, the trial design for the drug was also questionable. The study, which was set to incorporate up to 6,500 patients to receive either varespladib with Lipitor and standard of care or just placebo and Lipitor over 16 weeks, was both smaller and of much shorter duration than other cardiovascular trials, which can go on for years. It could have been this treatment time and small patient population that meant the trial did not show any benefits at the interim stage.

Picking up the torch

A drug similar to varespladib is GlaxoSmithKline’s darapladib, a LpPLA2 inhibitor, which is in two huge phase III trials for chronic heart disease. In contrast to Anthera’s trial Glaxo has enrolled almost 30,000 patients; results should emerge in 2013 and 2014. The future of the PLA2 pathway in preventing coronary events now lies in the hands of Glaxo.

Perhaps the share price fall for Anthera had been due to the more enthusiastic analysts - step forward Canaccord Genuity - in the market predicting the drug could potentially have peak sales of $2.2bn. Others such as Leerink Swann had not factored in any sales for the experimental treatment.

But what the slamming on the development brakes for varespladib means is that all of Anthera’s hopes now lie in the hands of blisibimod. The drug, unlike its sibling, managed to pass the futility test of its interim analysis, giving hope that it could eventually get approval due to the lack of current lupus treatments on the market.

Its final test will be the reporting of full phase II data for the Pearl-SC trial by the end of the second quarter.

Small hope

Blisibimod is potentially a challenger to latest market entrant Benlysta because it is a pan-B cell activating factor (BAFF) peptidbody, which unlike the Human Genome Sciences drug binds to both membrane bound and soluble BAFF, which is thought to be associated with a wide range of autoimmune diseases, including lupus.

It is hoped the dual BAFF suppression could mean the drug performs well in acute patients and also potentially reduces steroid use, something that would set it apart from the slow selling Benlysta. The drug also benefits from a more convenient mode of action of a monthly injection versus the monthly infusions of Benlysta.

If the results of the Pearl-SC trial are positive, Anthera shares should start to rise again, but it is hard to see them returning to the levels of before the varespladib news. With over $90m in cash on the balance sheet the group has enough cash for the time being.

Positive data is almost certain to be the start of the search for a marketing partner to take blisibimod into phase III trials, but this will now be done from a much weaker bargaining position.

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