AstraZeneca’s newest asset, the hyperkalaemia agent ZS-9, stumbled out of the gate just a day after the group committed $2.7bn to take out its owner, ZS Pharma. Long-term safety data released at Kidney Week raised questions about its adverse events profile, handing a potential advantage back to Relypsa's competitor, Veltassa.
The FDA will not decide on the ZS project for months, so perhaps more mature results will reassure regulators about the incidence of hypertension and oedema seen in the early data cut. But this misstep will not soothe Astra investors looking for the UK group to improve on a disappointing corporate development track record.
By contrast, Astra’s counterparts at Actelion must have breathed a sigh of relief over the weekend as the interim findings were revealed. The Swiss group missed out on ZS, but now does not have the worry of what the remaining data will say; moreover, it still has the cash to make a play on Relypsa or other companies that might take its fancy (AstraZeneca pips Actelion to ZS Pharma, November 6, 2015).
The ZS data come from a long-term safety study of ZS-9, a non-absorbed zirconium silicate designed to trap potassium ions and thus lower blood levels. The agent helped patients establish normal potassium levels in the acute phase and maintain them for a year, with 99% reaching it in the acute phase. The number of patients that have reached the 52-week endpoint so far – 61 of 683 – mean that this still is an immature trial.
But the most significant concern should arise from the adverse events analysis, in which 7% of patients developed hypertension and 7.7% peripheral oedema. With such a small share of patients reaching the 12-month endpoint there is a risk that the adverse events rate will climb.
This has been taken as a boost for Veltassa, which had its own difficulties on US approval on the inclusion of a black box warning of drug-drug interactions if other agents are taken within six hours of a Veltassa dose. Relpysa shares rose 10% to $20.67 in early US trading this morning, while Astra’s shares slid 1% to £41.68 in mid-afternoon trading in London.
The latter’s fall came in spite of positive new analyses from its gout project lesinurad being released at the American College of Rheumatology meeting.
What Relypsa has on its side is a similar-looking efficacy profile, no hypertension and only a mild oedema occurrence, offering a potential differentiator should ZS-9 be launched on a schedule that sees the US FDA making a decision by May 26, 2016.
The agency will no doubt be eager to see more mature safety data. With the signals seen so far, some industry watchers have suggested that the decision deadline might get pushed back – at the October 10, 2015 cut point, around 300 of the 683 enrolees had yet to reach 19 weeks of follow-up, meaning that their data will probably not be available by May 26.
Whether Astra had access to these data before signing on the dotted line is anybody’s guess. It might be better to appear surprised than unwise, but either way it does not look good.