Upcoming events – Dermira and Ziarco to show some skin
Welcome to your weekly digest of approaching regulatory and clinical readouts. The dermatology specialist Dermira is facing key readouts for its two solo projects, and expects to report results from a phase IIb trial with its acne gel DRM01 by the end of May; this should be quickly followed by phase III data on DRM04, a topical wipe for excessive underarm sweating.
Meanwhile, phase II results with Ziarco’s lead candidate, ZPL-3893787, in atopic dermatitis are due this quarter.
Three doses of DRM01 are being tested against placebo in the 400-patient phase IIb study, with the goal of finding the optimal dose for phase III trials. Assuming that the results are positive, phase III could start in the fourth quarter.
The primary endpoints of the phase IIb trial are change from baseline in the number of inflammatory and non-inflammatory lesions, and the proportion of patients achieving at least a two-point improvement in the investigator’s global assessment score, at 12 weeks.
Dermira will be hoping that DRM01, which inhibits sebum by blocking acetyl coenzyme-A carboxylase, can replicate positive phase IIa results. It is forecast to be Dermira’s best-seller, with Leerink analysts forecasting 2022 revenues of $240m and giving it a 70% probability of success. Citi analysts are less bullish, putting 2022 sales at $100m and its chance of success at 25%.
However, it will not be Dermira’s first product to market. That honour is likely to go to DRM04, an anticholinergic agent designed to inhibit sweat production.
The phase III Atmos-1 and Atmos-2 trials are comparing treatment with DRM04-containing wipes versus placebo wipes over four weeks. The primary endpoints are change in gravimetrically measured sweat production and the proportion of patients with at least a four-point improvement in the axillary sweating daily diary.
A long-term open-label study, Arido, is also ongoing. Dermira hopes to submit DRM04 to the FDA in the second half of 2017.
But although DRM04 is at a later stage, analyst expectations are more muted, with 2022 revenues pegged at $148m by the Leerink analysts but just $81m by Citi. The latter noted that sales might be held back by lack of patient awareness of the disorder.
Skin in the game
Meanwhile, Ziarco is preparing to report data from a phase IIa trial of ZPL-3893787 – also known as ZPL-389 – in moderate to severe atopic dermatitis. The company hopes to show an improvement over placebo in pruritus, or itching, at eight weeks.
If successful, the proof-of-concept study could help the company bag a partner for the oral selective histamine H4 antagonist, which recently also started a phase IIa trial in psoriasis and could be used in other diseases including asthma and allergic rhinitis.
The privately held Ziarco already has a link with Pfizer – it licensed ZPL-389 and other compounds from the company in 2012, while founder and chief executive Mike Yeadon previously led Pfizer’s allergy and respiratory research unit. Pfizer Ventures also participated in Ziarco’s 2014 $33m series B funding round, along with Amgen Ventures.
One unlikely partner is Johnson & Johnson, which has the other most advanced H4 blocker, according to EvaluatePharma: JNJ 38518168, or toreforant, is in phase II for asthma and psoriasis.
But both ZPL-389 and toreforant look set to be beaten to the market by Sanofi/Regeneron's interleukin inhibitor dupilumab, which just reported positive results from two phase III studies, putting it on course to become the first systemic therapy approved for atopic dermatitis.
Ziarco has other pipeline hopes. Behind ZPL-389 are ZPL-5212372, a topical cPLA2 inhibitor being developed in psoriasis and atopic dermatitis slated to start clinical trials in mid-2016, and ZPL-868087, an oral H3 antagonist for allergic rhinitis, which the company says is phase I ready.
Positive results with ZPL-389 could mean an injection of cash – either from a partner or another financing round – which would help progress both this asset and others in earlier-stage development.
|DRM01||Phase II dose-ranging study||NCT02431052|
|ZPL-3893787||Phase II study in atopic dermatitis||NCT02424253|
|ZPL-3893787||Phase II study in psoriasis||NCT02618616|