MALVERN, Pa.—Aclaris Therapeutics Inc., a dermatologist-led clinical-stage pharmaceutical company focused on defining new standards of care in medical and aesthetic dermatology, announced Nov. 5 that two pivotal Phase 3 trials of its lead product candidate A-101 40% Topical Solution (A-101), a novel treatment for seborrheic keratosis (SK), met all primary and secondary endpoints of each trial, achieving clinically and statistically significant clearance of SK lesions.
The two trials, SEBK-301 and SEBK-302, enrolled 937 patients in total and were conducted at 34 centers in the United States. The trials were identical in design and evaluated the safety and efficacy of A-101 compared to vehicle placebo in patients with four target SK lesions on the face, trunk and extremities. Of the 937 patients enrolled, 467 patients received A-101 and 470 patients were administered placebo. Investigators assessed the clearance of SK lesions using the validated four-point Physician Lesion Assessment (PLA) rating scale, which characterizes lesions as either clear (PLA=0), near clear (PLA=1), thin (PLA=2), or thick (PLA=3). Patients in each trial had four target SK lesions, including at least one on the face and at least one on the trunk or extremities. Each lesion received up to two treatments three weeks apart.
Overall, results from the combined trials showed 51.3 percent of lesions treated with A-101 were assessed as clear or near clear (PLA<1) at trial completion versus 7.3 percent of lesions in the placebo group. Notably, 65.3 percent of lesions on the face treated with A-101 were assessed as clear or near clear at trial completion versus 10.5 percent of lesions in the placebo group.
The primary endpoint of both trials was the percentage of patients treated with A-101 who achieved clearance (PLA=0) of all four target SK lesions. In the SEBK-301 trial, 4 percent of patients treated with A-101 achieved clearance of all four target SK lesions; in the SEBK-302 trial, 7.8 percent of treated patients achieved clearance of all four target SK lesions. None of the patients administered placebo achieved clearance of all four target SK lesions in either trial.
The secondary endpoint of both trials was the percentage of patients treated with A-101 who achieved clearance (PLA=0) of at least three of the four target SK lesions. In the SEBK-301 trial, 13.5 percent of patients treated with A-101 achieved clearance of at least three of the four target SK lesions; in the SEBK-302 trial, 23 percent of treated patients achieved clearance of at least three of the four target SK lesions. None of the patients treated with placebo achieved this endpoint. Clearance of three out of four target lesions is the primary endpoint that Aclaris has agreed upon with European Union (EU) regulators as a basis for approval. Based on these results, Aclaris plans to submit a Marketing Authorization Application in the EU in mid-2017.
An ancillary endpoint was the mean per-patient percentage of target lesions treated with A-101 who achieved clear or near clear of all target SK lesions (PLA<1). In SEBK-301, 47.5 percent of patients treated with A-101 achieved clear or near clear versus placebo which was 10.2 percent. In SEBK-302, 54.3 percent of patients treated with A-101 achieved clear or near clear versus placebo which was 4.7 percent.
“I see many SK patients who lack confidence in their appearance, especially those who have lesions in visible areas such as the face and neck,” said trial investigator Dr. Zoe Draelos. “For patients who seek to improve their appearance, a treatment that can achieve clearance or near clearance of lesions while delivering a favorable aesthetic result would represent a significant advance in the standard of SK treatment.”
SK lesions are common, non-cancerous skin lesions that impact more than 83 million Americans and frequently appear in highly visible locations such as the face or neck. The lesions are typically characterized by a waxy, scaly, elevated appearance and can vary in color from light tan to dark brown or black. SK lesions can have an adverse physical and emotional impact on patients. Existing treatments are invasive, often painful, or have undesirable outcomes like scarring or dyspigmentation.
“We are extremely pleased by these top-line results,” said Aclaris’ president and CEO, Dr. Neal Walker. “We had a productive pre-NDA meeting with the U.S. Food and Drug Administration earlier this year and look forward to submitting a New Drug Application to the FDA in the first quarter of 2017. We are committed to bringing this important new treatment to patients and their physicians.” If approved, A-101 would be the first FDA-approved topical treatment for SK.
There were no treatment-related serious adverse events among patients treated with A-101. The most common adverse events were nasopharyngitis and sinusitis, which were determined to be unrelated to A-101.
Local skin reactions, if present, were predominantly classified as mild. The rates of hypopigmentation, hyperpigmentation, and scarring classified as greater than mild were less than one percent in all groups in both trials.
Additionally, Aclaris announced that initial safety results from an open-label safety trial of A-101 (SEBK-303) were consistent with the SEBK-301 and SEBK-302 trials. The SEBK-303 trial enrolled 147 patients at 10 sites across the United States.
“This safety profile in these trials is compelling since there has been a significant need for an effective, non-invasive SK treatment without long-term pigmentary changes,” said Walker.
SOURCE: Aclaris Therapeutics news release