Ascletis Pharma’s acne pill has scored a phase 3 win, leading the Chinese biotech to claim the Sagimet Biosciences-sourced drug can hold its own against FDA-approved products like Seysara and doxycycline.
The Chinese study saw 480 patients with moderate to severe acne vulgaris receive either a once-daily 50-mg dose of the oral fatty acid synthase inhibitor denifanstat or placebo for 12 weeks. The trial hit all three of its primary endpoints, including a 18.6% placebo-adjusted increase in the proportion of patients who achieved success as defined by a skin clearance score.
Specifically, 33.2% of patients receiving denifanstat were assessed as having clear or almost clear skin at Week 12, compared to 14.6% of patients on placebo.
The average reduction in skin lesions in the denifanstat group was 57.4% compared to 35.4% for those on placebo. When it came to a reduction in inflammatory lesions, the drop was 63.5% and 43.2%, respectively.
While the trial was not designed to make head-to-head comparisons with existing acne products, Ascletis laid out its data alongside past results for potential competitors. This included comparing denifanstat’s 18.6% placebo-adjusted treatment success to 9.4% for Almirall’s Seysara, doxycycline’s 6.7% and 11.6% for clascoterone cream.
Ascletis pointed to these comparisons as evidence that denifanstat “has the potential to be a first-in-class, once-daily, oral acne therapeutic, potentially offering both exceptional efficacy and patient compliance with a favorable safety and tolerability profile.”
As an oral option, Ascletis also hopes denifanstat could ensure better adherence from patients than the current crop of topical treatments.
When it came to safety, the denifanstat and placebo cohorts had a similar profile, the biotech said. The only treatment-related adverse events that affected slightly more than 5% of patients in the denifanstat arm were dry skin and dry eye.
The idea behind denifanstat is to decrease cytokine secretion in order to inhibit the production of facial sebum, which is an underlying cause of acne. It means that, unlike some other acne treatments, denifanstat doesn’t have the potential to lead to antibiotic resistance or the off-target effects that can be seen with tetracycline antibiotics, Ascletis said.
“We are extremely pleased with the topline results of our phase 3 trial,” Ascletis CEO Jinzi Jason Wu, Ph.D., said in the release.
“Denifanstat tablets demonstrated impressive efficacy beyond treatment success, showing significant reductions in total lesion count, inflammatory lesion count, and non-inflammatory lesion count,” Wu added. “We are excited to be submitting this innovative treatment with the China National Medical Products Administration soon.”
Ascletis licensed the China rights to denifanstat from Sagimet back in 2019 with the initial aim of exploring the drug in a liver disease called metabolic dysfunction-associated steatohepatitis. Work on this indication appears to have stalled, with Ascletis stating in March that the company will “make further assessment and seek opportunities to maximize the value of this program.”
Antiviral, cancer and liver disease drug candidates were central to Ascletis’ strategy when the company went public in 2018. However, the biotech suffered setbacks in the clinic in its original core areas, including axing hepatitis B and liver disease programs. More recently, Ascletis has unveiled and quickly advanced a weight loss pipeline that features oral and subcutaneous formulations of a GLP-1 receptor agonist, leading the biotech to formalize its pivot to metabolic disease earlier this year.