Latest Indication For Soliris And U.S. Regulators Decide On ZS-9

Includes: ALXN, AZN, RLYP
by: EP Vantage

Welcome to your weekly digest of approaching regulatory and clinical readouts. Results from the phase III Regain trial testing Alexion’s (ALZN) Soliris in myasthenia gravis will be reported at the International Congress of Neuromuscular Diseases in July, and positive results in new indications are needed to boost franchise growth.

Meanwhile, AstraZeneca’s (NYSE:AZN) hyperkalaemia project ZS-9 will undergo an FDA decision on May 26. Safety issues arose from immature data in a phase III trial, and while forecasts set the asset as market leader the regulators will need reassurance first.


Last year worldwide sales of Soliris, an orphan drug, were $2.6bn. According to consensus sales forecasts from EvaluatePharma they are expected to more than double to $5.6bn by 2022. It is marketed for paroxysmal nocturnal haemoglobinuria and haemolytic uraemic syndrome, and much of the growth is expected to come from new indications.

One such indication is refractory generalized myasthenia gravis, an autoimmune neuromuscular disorder that results in muscle weakness, currently treated with acetylcholinesterase inhibitors and immune therapies. Refractory patients experience frequent relapses and often develop severe side effects to treatments.

The primary endpoint of the 92-patient, double-blind, placebo-controlled Regain trial is change in total myasthenia gravis activities of daily living (MG-ADL) score. Results are expected on July 7 at the International Congress of Neuromuscular Diseases in Toronto, Canada.

The previous phase II trial tested a different primary endpoint called the quantitative myasthenia gravis disease severity (QMG) score. In the 14-patient study 86% of Soliris-treated patients achieved a three-point reduction in their QMG score after 16 weeks of treatment, versus 57% of placebo-treated patients.

Leerink analysts expect high correlation between the endpoints from the two trials, and have also boosted their probability of success from 65% to 75%.

Other Soliris studies due to read out include Protect in delayed graft function and Prevent in neuromyelitis optica, with data later this year or in early 2017. Soliris is expected to be the biggest rare disease play by 2020, if new indications can deliver (Industry work on rare diseases continues to bear fruit, March 3, 2016).


AstraZeneca got ZS-9 through its purchase of ZS Pharma at the end of last year for $2.7bn, but safety issues emerged shortly afterwards (Forehead slaps in order for Astra as data dwarf $2.7bn deal, November 9, 2015).

ZS-9 is designed to trap potassium ions and thus lower levels in the blood. In the phase III trial the agent helped patients establish normal potassium levels in the acute phase of the study and maintain them for a year, with 99% reaching the goal in the acute phase. At the time only 61 of the 683 patients had reached the 52-week endpoint, so the data were still relatively immature.

The most significant concern was from adverse events, with 7% of patients developing hypertension and 7.7% peripheral oedema. With such a small share of patients reaching the 12-month endpoint there was a risk that the adverse events rate could climb.

The FDA did not call an advisory committee and will meet on May 26 to decide ZS-9's fate; Astra will hope that more mature data will reassure regulators. ZS-9 is forecast to become the hyperkalaemia market leader by 2022, with sales set to reach $849m, according to consensus from EvaluatePharma.

The next biggest is Relypsa’s (NASDAQ:RLYP) Veltassa, which was launched at the end of last year for hyperkalaemia; this has a similar-looking efficacy profile to ZS-9, but without the risk of hypertension and only a mild oedema occurrence. However, it does come with a black-box warning about the risk of drug-drug interactions.

Relypsa plans to submit an sNDA by mid-2016 requesting a label change based on phase I drug-drug interaction studies. Whether this will change its commercial aspect is not known, and 2022 forecasts sit some way behind ZS-9 at $529m.


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