Ziarco Lacks Sparkle In Atopic Dermatitis

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by: EP Vantage

Ziarco’s oral atopic dermatitis contender ZPL-3893787 failed to meet its primary endpoint in a proof-of-concept trial, so the company must hope that signs of efficacy will be enough to help it reel in a partner. The private UK group highlighted secondary endpoint success and said it would start a phase IIb study in the second half of this year.

The question is whether this is good enough to secure a partner for ZPL-389. A year or two ago the dermatology specialist Valeant (NYSE:VRX) would have seemed an obvious choice, but business development is now off the table as the company deals with its own problems. And any potential partner might want to wait for more robust data before making a move.

This does not faze Ziarco. Its chairman, Mike Grey, told EP Vantage that the company had the cash to get ZPL-389 ready for phase III in both atopic dermatitis and a second indication, psoriasis. The project is already in a phase IIa trial in the latter, with results due in the first half of next year.

Let battle commence

Hooking a partner is essential for Ziarco, which would find it a struggle to market ZPL-389 alone, not least because it will likely be going up against Sanofi (NYSE:SNY)/Regeneron's (NASDAQ:REGN) interleukin inhibitor dupilumab. The latter looks set to become the first systemic drug to be approved for atopic dermatitis after reporting positive phase III results earlier this year; the companies are planning a regulatory filing in the third quarter.

Another potential rival to ZPL-389 is Johnson & Johnson’s fellow H4 blocker JNJ 38518168, or toreforant, which is in phase II for asthma and psoriasis.

And Pfizer (NYSE:PFE), which licensed ZPL-389 to Ziarco back in 2012, recently acquired Anacor Pharmaceuticals (NASDAQ:ANAC) and its eczema cream crisaborole, which is under review by US regulators – perhaps decreasing its appetite for further dermatology deals (Pfizer looks elsewhere in derm, finds Anacor, May 16, 2016).

In spite of the competition, Mr. Grey believes that there is a niche for ZPL-389: “Dupilumab, as an injectable biologic, will be conserved for the most severe patients.”

Meanwhile, topical treatments are more suited to those with milder disease. “The average body surface area affected in our phase II study was 44% – if you can imagine having to apply a topical treatment to half your body twice a day, you can see that an oral drug would be very attractive to patients.”

Mr. Grey concluded: “There’s a real interest in an oral drug that can address moderate to not very severe patients who wouldn’t be addressed by any of the new innovations.”

Not so EASI

One thing seems certain: ZPL-389 must do better than in the phase IIa study, in which it failed to show a significant improvement over placebo in the primary endpoint of pruritis, or itching, measured using a 10-point numerical rating scale completed by patients.

However, the study, presented at the European Academy of Allergy and Clinical Immunology congress, did show a benefit on the eczema area and severity index (EASI), as well as other secondary endpoints including the Scoring Atopic Dermatitis or SCORAD scale.

Eight-week results from phase IIa trial of ZPL-389

Endpoint

ZPL-389

Placebo

p value

Primary endpoint

Reduction in numerical rating scale for pruritis

~42%

~37%

Not significant

Secondary endpoints

Reduction in EASI

50%

27%

p=0.01

Reduction in SCORAD

43%

26%

p=0.004

Reduction in body surface area affected by atopic dermatitis

18%

12%

p=0.04

Mr. Grey blamed a high placebo response for the primary endpoint miss, saying the response in the active arm was similar to that seen with dupilumab. The phase IIb trial might not be scuppered by the same issue as it will use EASI as its primary endpoint.

More data could help secure a partner – but Ziarco is already seeing “a lot of interest from companies”, says the chairman. “So while we’re preparing to start a phase IIb study by the end of this year … we could be persuaded to think about an alternative course.”

Potential buyers could also be interested in Ziarco’s second candidate, ZPL-521, which it plans to take into a proof-of-concept phase I/II trial this year. The non-steroidal topical therapy targets mild to moderate atopic dermatitis, the same population as Anacor/Pfizer’s crisaborole.

But for now, bigger companies might be wary of Ziarco. The phase IIb study will need to be a success for the UK company to take ZPL-389 forward into phase III, with or without the help of a partner.

Ziarco’s pipeline

Project

Mechanism

Indication

Status

Trial details

ZPL-389

Oral H4 antagonist

Atopic dermatitis

Phase IIa

NCT02424253

Psoriasis

Phase IIa

NCT02618616

ZPL-521

Topical cPLA2 inhibitor

Atopic dermatitis

Phase I/IIa to start H2 2016

N/A

ZPL-868

Oral H3 antagonist

Allergic rhinitis

“Phase I ready”

N/A