Shares of Aclaris Therapeutics Inc. (NASDAQ:ACRS) rose 64% to $1.80 Tuesday on news that A-101, its topical treatment of verruca vulgaris, or common warts, met both the primary and all secondary efficacy endpoints of the phase III THWART-2 trial, the first of two pivotal studies intended to support an NDA filing for the drug, a high-concentration topical hydrogen peroxide solution. The other trial, THWART-1, is expected to read out in the fourth quarter.
The company has two commercial products, Allergan plc-sourced Rhofade (oxymetazoline hydrochloride) and a 40% topical hydrogen peroxide solution it developed called Eskata. However, only Rhofade remains on the market after Aclaris discontinued Eskata in August, just months after its May launch. Sales of the solution, intended for office-based treatment of raised seborrheic keratosis, proved insufficient to sustain continued commercialization, the company said.
Similar to Eskata, A-101 is a 45% topical hydrogen peroxide solution. But in addition to targeting a different indication, it is intended for a different setting: self-administration. On an annual basis, about 2 million people in the U.S. are diagnosed with common warts, the company said.
In THWART-2, the company enrolled 502 participants who had one to six warts at baseline, randomizing them to self-administer either A-101 or a placebo vehicle twice a week over eight weeks, for a total of 16 treatments. The trial achieved its primary endpoint by helping a higher proportion of those receiving A-101 clear their warts by day 60, compared to the proportion of participants assigned to the placebo arm (p<0.0001). Warts were assessed using the Physician Wart Assessment scale, a four-point scale of the investigators' assessment of the severity of all treated warts.
All secondary efficacy endpoints of the study also favored A-101, including complete clearance of all warts at day 137 for those treated with the medicine (p=0.0001); the mean per subject percent of treated warts cleared at day 137 (p<0.0001); clearance in subjects with a single baseline wart at day 60 (p=0.0006); and time to complete clearance of all warts (p<0.0001).
Though the active solution met all the efficacy endpoints of the study, treatment-related application site adverse events (AEs) were significantly higher in the A-101 arm, with 53.4% receiving the active solution reporting AEs vs. 8.4% in the placebo group. The most common AEs were application site pain, pallor, erythema, pruritus, scabbing and erosion, though no participants withdrew from the study because of them.
Aclaris President and CEO Neal Walker said, "We believe these results will be of interest to partners seeking to commercialize A-101," a goal the company has pursued since last year and continues to work on following the completion of a strategic review and refocusing of company resources on its immuno-inflammatory development programs. It's also seeking a commercial partner for Rhofade, a treatment for persistent facial redness it acquired from Allergan in November 2018.
Meanwhile, the company is also seeking a development and commercialization partner for ATI-501 and ATI-502, investigational JAK1/3 inhibitors for the potential treatment of alopecia in-licensed from Rigel Pharmaceuticals Inc. in 2015.
In June, ATI-502, a topical candidate, failed to achieve statistical superiority at the primary or secondary endpoints of a randomized, vehicle-controlled trial in people with alopecia areata (AA) due to high rates of disease resolution in vehicle-treated patients, the company said. ATI-501, a topical version of the medicine, fared better in a separate randomized, placebo-controlled phase II study, reading out in July as having achieved statistically significant improvement over placebo in several measures of hair growth, including the primary endpoint and certain secondary endpoints of that trial. (See BioWorld, Nov. 17, 2016.)
The company's shares have fallen 75.6% year to date and hit a 52-week low of 74 cents on Aug. 15. Unsurprisingly, management is working to lower the company's expenses and eliminate what Walker called "the inherent risks and investment related to maintaining a commercial infrastructure," in a Sept. 5 statement. The company's plan includes the termination of 86 employees across the organization as well as a discontinuation of efforts to promote Rhofade with sales staff. A representative of the company did not respond to an interview request Tuesday.
Looking ahead, the company plans to host an R&D day focused on its pipeline of candidates for immuno-inflammatory diseases on Sept. 27. Topics to be covered will include its kinase-focused Kinect drug discovery platform, a product of its August 2017 acquisition of Confluence Life Sciences Inc.; ATI-450, an oral alternative to injectable anti-cytokine biologics and JAK inhibitors; ATI-1777: a topical JAK1/3 Inhibitor; ATI-2138, an ITK/TXK/JAK3 inhibitor for autoimmune disease; and gut-restricted inhibitors of ITK and/or JAK kinases as drugs for inflammatory bowel disease.