Aclaris Therapeutics Inc. is aiming for a first quarter NDA filing – and a mid-2017 marketing authorization application – for A-101, a topical high-concentration hydrogen peroxide formulation, for seborrheic keratosis (SK), on the back of successful results from two phase III trials.

The studies, dubbed SEBK-301 and SEBK-302, enrolled a total of 937 patients in the U.S. and compared A-101 (40 percent topical solution) to placebo. Patients had to have four target lesions, including at least one on the face and at least one on the trunk or extremities, with each lesion receiving up to two treatments three weeks apart. The primary endpoint was based on a four-point Physician Lesion Assessment (PLA) rating scale, and for patients to meet response criteria on the primary endpoint, all four lesions had to be evaluated as clear (PLA=0) by the end of the study period.

"If three lesions were completely clear and even if one of the lesions was near clear [a measurement defined as PLA=1], that subject was not counted as a responder for the purposes of the primary regulatory endpoint," stressed Stuart Shanler, Aclaris' co-founder and chief scientific officer. Those stringent criteria made the results all that more impressive.

In the SEBK-301 study, the percentage of patients who achieved PLA=0 for all four target lesions was 4 percent in the A-101 group (p < 0.002), while 7.8 percent of A-101-treated patients achieved PLA=0 in the SEBK-302 trial (p < 0.0001). No patients in the placebo group of either study achieved clearance of all four target SK lesions. And the safety profile for A-101 looks good, too, with no treatment-related serious adverse events reported, with only mild local skin reactions, if any. Plus, the rates of hypopigmentation, hyperpigmentation and scarring classified as greater than mild were less than 1 percent in all groups in both trials.

During a Tuesday conference call with investors, Shanler also provided before and after photos of patients, including two examples of facial SK lesions judged at baseline to be PLA=3, or a thick lesion, which resolved by end of treatment to PLA=0. The aesthetic results, in particular, "are quite outstanding," he said. "In fact, results such as these are actually difficult to replicate with the currently available treatment modalities."

There are no FDA-approved therapies for SK lesions, which are estimated to affect more than 83 million Americans and, while noncancerous, can be unsightly, often described as waxy and scaly in appearance and varying in color from light tan to dark brown or black. Existing options for patients are limited to painful or invasive procedures that carry their own aesthetic risks. Pigmentation effects resulting from cryosurgery, for instance, run in rates "north of 50 percent," according to "what we have found looking at the literature," said Aclaris' co-founder, president and CEO, Neal Walker. Scarring is likely in cryosurgery as well, with rates "north of 25 percent," even with the use of wound care. "We used no wound care in our studies," he added.

The secondary endpoint for both trials – the primary endpoint required by European regulators – was the percentage of patients achieving clearance in at least three of the four target SK lesions. In the SEBK-301 trial, 13.5 percent of A-101-treated patients achieved that endpoint (p < 0.0001), while in the SEBK-302 trial, 23 percent of patients hit the mark (p < 0.0001). Again, none of the placebo-treated patients achieved the endpoint.

Those "strong" data suggest "that A-101 is an approvable product in the U.S. and Europe," wrote Jefferies analyst David Steinberg in a research note. He added that the product has the potential to become the new standard of care for SK lesions.

Given the large market opportunity, "we envision a brisk launch for A-101 in the SK indication and continue to forecast peak sales approaching $500 [million]," Steinberg said.

SIZING UP THE MARKET

Whether it will be Malvern, Pa.-based Aclaris that actually commercializes A-101 remains to be seen. The company, which ended the third quarter with about $84 million in cash, equivalents and marketable securities, enough to get through the fourth quarter of 2017, is already looking to pad its coffers, filing for a $65 million public offering late Wednesday. But dermatology-focused companies have been a favorite acquisition target of big pharma in the last few years, in particular Allergan plc, which most recently agreed to shell out $639 million to buy Vitae Pharmaceuticals Inc., shortly after the latter reported promising phase IIa data for psoriasis candidate VTP-43742. (See BioWorld Today, Sept. 15, 2016.)

Dublin-based Allergan also bought Kythera Biopharmaceuticals Inc. last year in a deal valued at about $2.1 billion, gaining rights to FDA-approved fat-burning injectable drug Kybella (ATX-101; deoxycholic acid). And shortly before he started up Aclaris, Walker sold previous firm Vicept Inc., which had been working on a candidate for rosacea, to Allergan for $275 million. (See BioWorld Today, June 18, 2015.)

Aclaris "fits our M&A thesis," Jefferies' Steinberg noted in a September research report. "There have been 22 acquisitions of dermatology [companies] over the past six year. We believe [Aclaris] fits this profile as a potential strategic asset in both aesthetic and medical dermatology."

Other big dermatology players include Spain's largest drugmaker Almirall SA, which shifted its primary focus to dermatology after divesting its respiratory disease portfolio to Astrazeneca plc in 2014, and Danish firm Leo Pharma A/S, which has been busy negotiating deals in the space, picking up rights to tralokinumab, an interleukin-13 (IL-13) inhibitor, in atopic dermatitis, and the troubled IL-17 receptor inhibitor brodalumab in plaque psoriasis from Astrazeneca in July and partnering with Argen-X NV last on an early stage antibody drug program for inflammatory skin conditions. (See BioWorld Today, July 31, 2014, May 22, 2015, and July 5, 2016.)

The addition of A-101 to any could be a boon to any of those firm's pipelines if the market dynamics prove as favorable as Aclaris describes.

Brett Fair, the company's senior vice president of commercial operations, said SK lesions are the most common benign skin condition seen by dermatologists, which represent a concentrated physician base. "Our market research findings indicate a high level of interest in a topical, noninvasive treatment of SK that offers good aesthetic outcomes," Fair explained. "Research findings also indicated willingness to pay out of pocket on behalf of patients."

In the meantime, Aclaris plans to work in improving the value proposition for A-101. While the two pivotal trials enrolled patients of every skin type, the most prevalent skin types were Fitzpatrick skin types 2 and 3, which represent fairer skin tones.

"We didn't get a large number of African-American patients," Walker acknowledged. Between the NDA filing and a regulatory decision, Aclaris plans to conduct a few other studies, including a study in a subset of patients with small SK lesions known as dermatosis papulosa nigra, or DPN, on the face. "We'll also target what are called stucco keratoses on the legs and we'll also be doing a full back segment. Those are all areas that we've maintained are important segments in the space and [will] allow us to start kind of honing in on some of the additional skin types that you can't get in a broader study."

Full data from a safety study are expected shortly, though Aclaris' interim look showed a profile consistent with the top-line results from both pivotal trials.

A breakdown of the data from SEBK-301 and SEBK-302 are expected later, though Aclaris reported additional top-line figures, including overall data from both trials, which showed 51.3 percent of lesions treated with A-101 were assessed as "clear" or "near clear," vs. 7.3 percent of lesions in the placebo group. "We have always maintained from the beginning that [the clear/near clear assessment] is the true practical clinical endpoint," Walker said.

Pooled data of facial lesions showed that 65.3 percent treated with A-101 were assessed clear/near clear vs. 10.5 percent in the placebo group.

An ancillary endpoint, defined as the mean per-patient percentage of target lesions treated with A-101 achieving clear/near clear of all target SK lesions, showed that 47.5 percent of A-101-treated patients vs. 10.2 percent of placebo patients (p < 0.0001) achieved the endpoint in the SEBK-301 trial, while the SEBK-302 study showed clear/near clear achievement in 54.3 percent of A-101 patients vs. 4.7 percent of placebo patients (p < 0.0001).

Shares of Aclaris (NASDAQ:ACRS) closed Wednesday at $22.86, down 57 cents.