All eyes on brodalumab fallout

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After Amgen’s shock decision on Friday to dump the AstraZeneca-partnered psoriasis antibody brodalumab, citing risk of suicide, attention should turn to competing agents from Novartis and Lilly and the question of whether this could be a class effect.

True, there are mechanistic differences: brodalumab hits the IL-17 receptor, while Novartis’s Cosentyx and Lilly’s ixekizumab bind the IL-17 ligand. However, EP Vantage has learned that since Cosentyx’s US launch in January there have been two reports of suicide attempts by patients on the Novartis drug.

The reports came via the healthcare information company AdverseEvents, which scrutinises the US FDA’s Adverse Event Reporting System (FAERS) and makes frequent freedom-of-information requests to access the agency’s data.

Brian Overstreet, AdverseEvents’ president, said his company’s scouring of the FAERS had thrown up two Cosentyx suicide attempts so far. He added that another freedom-of-information request would be filed today for more up-to-date data and to get a clearer picture of the possibility of a class effect.

As EP Vantage went to press Novartis had not responded to a request to comment on the two suicide attempts with Cosentyx.

Bolt from the blue

Until now there had been little to differentiate the three novel psoriasis MAbs, so Amgen’s announcement, at 5pm on the Friday before the Memorial Day weekend, came like a bolt from the blue (Lines drawn for coming IL-17 psoriasis fight, August 22, 2014).

In its statement Amgen said brodalumab, the first of five selected MAbs under a 2012 inflammation deal with Astra, would be handed back to the UK firm based on Amgen’s appraisal of events of suicidal ideation. Bank of America Merrill Lynch analysts said brodalumab’s Amagine-2 trial saw one suicide, and higher suicide attempt and ideation rates versus J&J’s Stelara.

In Amgen’s view this finding necessitates restrictive labelling and limits the available patient population. It is highly unusual for a discontinuing partner to spell out in such detail the reasons for pulling out, suggesting that the problem is very serious, and that this is not just an excuse to get Amgen out of funding development.

EvaluatePharma data indicate consensus sellside 2020 sales forecasts for Cosentyx, brodalumab and ixekizumab of $1.6bn, $907m and $519m respectively. The BoAML analysts wrote: “We do not [see] a class effect as Cosentyx has not been linked to suicide ideation.”

For Astra, however, this is a major setback; in its defence against Pfizer’s takeover attempt last year the group trumpeted the potential of brodalumab as an underappreciated asset that could bring in $0.5-1.5bn of peak revenues.

Astra said today that it would review data from brodalumab’s three pivotal Amagine trials and decide as soon as possible how to proceed. Ixekizumab was submitted with the FDA for moderate to severe plaque psoriasis in the first quarter, and a filing for the Astra/Amgen project was imminent.

Irrespective of Astra’s decision a big risk for Novartis and Lilly is if Amgen’s move triggers an FDA class-wide review. It is still possible, of course, that brodalumab’s action on the receptor subunit IL-17RA results in a broader effect versus Cosentyx and ixekizumab, which Lilly is at pains to point out targets IL-17A and does not bind cytokines IL-17B, IL-17C, IL-17D, IL-17E or IL-17F.

The full picture will not emerge until a thorough evaluation of the FAERS, and until the actual number of suicides or suicidal ideation incidents is spelled out in detail.

AdverseEvents is partly financed through venture capital provided by Evaluate Ltd, the parent company of EP Vantage.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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