Welcome to your weekly digest of approaching regulatory and clinical readouts. Before the end of March Dermira should release topline results from a phase IIb trial of lebrikizumab in atopic dermatitis, also known as eczema. The company is coming late to the disease, which is dominated by Sanofi/Regeneron’s blockbuster Dupixent, but it hopes to differentiate lebrikizumab, an anti-IL13 monoclonal antibody, from its now-entrenched rival.
For one thing, lebrikizumab could have a four-weekly dosing schedule, versus Dupixent’s two-weekly regimen. To have any chance of grabbing share from Dupixent, which sold €788m ($891m) last year, Dermira at the very least needs to show that its project is more convenient. Should lebrikizumab appear safer, more tolerable or even more effective, that would be even better.
The trial is testing 125mg and 250mg lebrikizumab doses in different combinations of loading and maintenance settings. The higher dose is also in a twice-weekly arm. The trial has recruited 280 patients and also includes a placebo group.
The different schedules mean that topline results could be hard to judge unless Dermira releases a lot of information up front. The primary endpoint is percentage change on the eczema area and severity index (EASI) from baseline to week 16, while key secondary measures include EASI75 and IGA scores. These last two were used as key measures to win Dupixent approval.
Any promising findings with lebrikizumab would need to be proven in phase III, of course, a costly undertaking for which Dermira is not fully funded. The company would also need to pay Roche a $20m milestone on starting any pivotal programme.
However, this could be offset by payments from Almirall. In February, the Spanish company paid $30m up front for an option on lebrikizumab in Europe. Should Almirall take this up, another $50m fee will become due to Dermira.
Underwhelming results with lebrikizumab a few years ago, when it was still being developed by Roche, have led to understandable scepticism, and any attempt to grab share from Dupixent would be expensive. Investors will want to see clear signs of differentiation.
|Dupixent's clinical record in atopic dermatitis|
|Solo 1, NCT02277743||Solo 2, NCT02277769|
|Dupixent 300mg Q2W||Placebo||Dupixent 300mg Q2W||Placebo|
|IGA 0 or 1||38%||10%||36%||9%|
|Source: US drug label.|
Conatus's second chance
Conatus and Novartis’s Nash project, the caspase inhibitor emricasan, has already failed one of its phase II trials, Encore-PH. The companies now have a couple more chances to turn things around, with mid-stage data from two studies due in the coming months.
The first readout, from the Encore-NF trial in patients with Nash fibrosis, is expected in the first half of the year. Then in mid-year data should follow from Encore-LF, in patients with decompensated Nash cirrhosis.
Encore-NF has enrolled 330 patients with stage F1-F3 fibrosis, randomised to receive emricasan 5mg or 50mg twice daily, or placebo. The primary endpoint is the proportion of patients achieving a one-stage improvement in fibrosis score, with no worsening of steatohepatitis, at week 72.
The trial will be classed a success if it returns a p value of 0.05 in either the F1-F3 or F2-F3 patient populations, Conatus has said. Fibrosis has five stages, with a score of 0 representing no scarring and 4 representing cirrhosis.
Meanwhile, the decompensated cirrhosis patients enrolled in Encore-LF have more advanced disease. The 210-patient study tests emricasan 5mg or 25mg versus placebo, and the primary endpoint is event-free survival. An event is defined as death, new decompensation events, or a four-point or greater increase in the MELD score, used to measure the severity of liver disease.
Nash therapy developers have failed to deliver a knockout result in 2019. Conatus could find scoring a win in Encore-LF a particularly hard task given Encore-PH’s results in a similar patient population.
News that Encore-PH had bagged a late-breaker slot at the upcoming Easl meeting in Vienna sent Conatus’s stock up an improbable 26% on Wednesday. But the group will need stronger results – and buy in from its partner, Novartis – to justify a move into phase III.
This story has been corrected to reflect the recent renegotiation of the Roche/Dermira deal, which reduced the phase III milestone payment to $20m from $40m.