Upcoming events – binary outcomes for Inflarx and Achieve

Welcome to your weekly digest of approaching regulatory and clinical readouts. The German company Inflarx has enjoyed a bumpy but positive 2019, its stock up 22% so far this year, mostly on expectations of a huge binary catalyst: readout of the blinded phase II Shine study of its lead project, IFX-1.

Shine tests four doses of IFX-1, an anti-C5a MAb, in hidradenitis suppurativa, a condition that causes abscesses and scarring on the skin. The primary efficacy measure is response versus placebo on the basis of the 16-week HiSCR score, and with data due towards the end of the current quarter investors must bear several factors in mind.

Most importantly, perhaps, hidradenitis suppurativa’s cause is unknown, though there is some suggestion that it is associated with elevated circulating levels of C5a, a complement factor. Inflarx’s theory is that C5a’s pro-inflammatory properties, such as damping down Tregs, cause immune system balance disruption.

Bulls point to a small, single-centre, open-label trial in which IFX-1 yielded a 75-83% HiSCR response at 8-20 weeks. Clearly this should be lower in a controlled study, and the question is what response will be enough to beat placebo with statistical significance.

Abbvie’s Humira is approved in hidradenitis suppurativa on the basis of 42-59% HiSCR responses, versus 16-28% for control, so this could be a target for Inflarx to beat.

The Inflarx bull thesis recently took a hit on reports that the old immunosuppressant colchicine could be an early treatment for the condition, but evidence is inconclusive.

Investors must also bear in mind Shine’s statistical analysis: rather than performing a simple test Inflarx plans to use multiple comparison procedure modelling to seek a dose-response relationship as well as a drug effect. Leerink analysts reckon this will not affect powering, however.

A final consideration is that it is unclear how big an indication hidradenitis suppurativa might be; Leerink had worked on the assumption of 200,000 US patients, but now suggest that it could be more prevalent. EvaluatePharma consensus sees IFX-1 generating $239m of sales in 2024, but first the project must succeed in the clinic.

Smoke signals?

Shares in Achieve Life Sciences have already increased more than threefold since the beginning of the year, and could be set to rise again if the Canadian nano-cap comes up trumps with topline phase IIb data for its smoking cessation asset cytisinicline, also known as Tabex.

The 254 patient Orca-1 trial is due to read out by the end of this quarter. The three-arm study is evaluating 1.5mg and 3mg doses of cytisinicline plus behavioural support, versus placebo plus behavioural support. The primary endpoint is a reduction in the number of cigarettes smoked during the treatment period, while secondary endpoints include smoking cessation rates, safety and compliance.

Cytisinicline is an alkaloid produced from the seeds of the laburnum plant, and interacts with nicotine receptors in the brain to reduce the severity of nicotine withdrawal. It has been available in Eastern Europe for over 40 years, but has not been formally approved in the EU or US, allowing it to be classified as a new molecular entity.

Because cytisinicline is a natural product it cannot be patented, but FDA approval would give five years' data exclusivity protection, while an EU green light would secure 10 years. Achieve is also working on new salt forms of the project.

So far cytisinicline appears to have dodged the safety issues that dogged the market leader, Pfizer's Chantix, which was given a black box warning in 2009 on reports of suicidal ideation; the warning was withdrawn in December 2016. But the drug, which last year sold $1bn, is due to lose patent protection in 2020, hitting future cytisinicline sales.

If cytisinicline does pass phase IIb two pivotal tests are planned for the end of 2019 and the second half of 2020, aiming to enrol a total of 2,300 patients. But Achieve only has enough cash to the end of the phase IIb trial. If a partner does not materialise investors should brace themselves for a fund-raising.