Future of AZ’s psoriasis drug in doubt after Amgen withdrawal

AstraZeneca (AZ) will be forced to make a difficult decision on its psoriasis drug brodalumab after Amgen pulled out of the development partnership.

Brodalumab had been tipped to reach peak sales in excess of $1 billion, but now Amgen has pulled out, citing concerns about suicide ideation and behaviour seen in some trial patients.

Amgen said these concerns would require ‘restrictive labelling’ – something which it clearly believed would scupper the drug’s chances in a very competitive psoriasis market.

“During our preparation process for regulatory submissions, we came to believe that labelling requirements likely would limit the appropriate patient population for brodalumab,” said Sean Harper, executive vice president of Research and Development at Amgen.

The drug works by targeting IL-17, and is one of a crowded field of new drugs. The molecule had also been under development for psoriatic arthritis, and axial spondyloarthritis.

Briggs Morrison, AZ’s head of Global Medicines Development and chief medical officer, said the company will evaluate data from its AMAGINE phase III trial, and make a decision ‘as soon as possible’.

The news is a major setback for AZ, which was counting on brodalumab being one of a new generation of top-earning molecules, desperately needed as its old blockbusters go off patent.

It is precisely 12 months since Pfizer conceded defeat in its attempted takeover of AZ, a feat the UK-based company helped secure thanks to confident forecasts of its independent growth.

Analysts confirmed the news was a blow. A Bloomberg report quoted Simon Mather, analyst at Barclays Plc: “The commercial perspectives are clearly very challenging… Amgen’s decision to terminate the brodalumab collaboration does little to increase confidence in AZN’s pipeline aspirations.”

Mather had projected peak sales of $880 million for the treatment, but has now removed it from his own forecasts for the firm.

If AZ were to press ahead with the drug, it would face stiff competition from other treatments. Novartis is in pole position in the IL-17 field, with its drug Cosentyx (secukinumab) approved in January.

Meanwhile Lilly is building momentum with its IL-17-blocking candidate ixekizumab, with Merck’s MK-3222 and Johnson & Johnson’s IL-23 inhibitor guselkumab in hot pursuit.

Questions have now been raised about whether other drugs in the IL-17 class could have the same side effects, though Novartis has already indicated that Cosentyx hasn’t produced similar signals.

The news comes just a few days after another potentially damaging safety warning: the FDA says that the SGLT2 class of diabetes drugs has been linked with cases of ketoacidosis, dangerously high levels of blood acids which can require hospitalisation. AZ’s Forxiga is one of the SGLT2 drugs in the frame, and could be hit if the US regulator demands labelling changes.

Amgen and AZ still have four other molecules in development as part of their partnership in inflammation, but none of these are as advanced as brodalumab. Amgen led on development and commercialisation for brodalumab and AMG 557/MEDI5872 (phase Ib for autoimmune diseases, such as systemic lupus erythematosus), while AZ’s biologics division MedImmune leads on MEDI7183/AMG 181 (phase II for ulcerative colitis and Crohn’s disease), MEDI2070/AMG 139 (phase II for Crohn’s) and MEDI9929/AMG 157 (phase II for asthma).

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