A safe, effective antibody therapy for acne vulgaris that treats both skin lesions and psychological comorbidities would represent a quantum advance in the management of this skin disease. XBiotech is using a subcutaneous injectable formula of its True Human™ antibody to safely and conveniently stop the chronic inflammation associated with acne - to help resolve both skin lesions and mental health issues associated with the disease.

The phase II clinical study, launched in 2012 and completed in 2013, evaluated treatment in moderate to severe acne vulgaris. The study was headed by leaders in the dermatology community, including Dr. Ronald Moy, recent President of the American Academy of Dermatology, former Co-Chief of Dermatology, and Chief of Dermatological Surgery at UCLA Medical Center.

Patients were assessed by measuring the number of skin lesions, as well as by tracking Investigator's Global Assessment (IGA). Psychological status was also measured through the use of the Hospital Anxiety and Depression Scale instrument, as well as other questionnaires.

Acne vulgaris affects more than 40 million persons in the US. Most adolescents suffer from some degree of acne as well as up to 51% of adults into their fourth decade. The underlying cause of acne is not clear, inflammation of pilosebaceous follicles is known to be a central feature of the disease; where in severe cases, subsequent cyst and nodule formation result in permanent scarring.

While most everyone is familiar with the skin manifestations, relatively few are aware that acne vulgaris is associated with serious psychological disturbances and in some cases even mortality due to suicide. In fact, depression and anxiety associated with acne is reportedly more severe in acne patients than in many other serious chronic, non-psychiatric medical conditions.

While a number of treatments for acne vulgaris exist, therapy for severe acne (isotretinoin) is associated with significant side effects, including exacerbation of depression, psychosis and even suicide ideation. No therapy even attempts to treat both the skin manifestations of acne as well as psychological complications.

The association of psychological difficulties and acne was made long ago, yet the mechanism to explain the link between these seemingly disparate processes was not forthcoming. Recent advances have now linked systemic inflammatory processes involved in skin lesion development to CNS disturbances.

Acne vulgaris onset involves the formation of the microcomedone, an assemblage of hypercornified and hyperkeratinized tissue within the pilosebaceous infundibulum that plugs the follicle. Several avenues of research point toward the chronic inflammatory cytokine IL-1α as playing a key role in microcomedone formation. In vitro stimulation of follicles with IL-1α leads to hypercornification, similar to that seen in comedone formation. Bacterial flora associated with acne is also known to stimulate IL-1α production from keratinocytes. Skin biopsies of acne vulgaris lesions indeed reveal the presence of IL-1α.

The role of IL-1α in acne suggests that antibody therapy could be expected to reduce inflammatory acne lesions. Additionally, new understanding of the role of IL-1α in inducing the foreboding associated with chronic inflammatory processes, also suggested that antibody therapy could reduce comorbidities of the disease.

In the hypothalamus, the fenestrated microvasculature allows interdigitating neurons to interact with circulating inflammatory moieties such as IL-1α. IL-1 receptors on these neurons can trigger the cells to signal the presence of danger signals, allowing cognition of the presence of injury. During protracted inflammation, this chronic danger signal results in the perception of anxiety or depression.

The True Human™ antibody under development for the treatment of acne provides a highly targeted blockade of IL-1α. Results from a recent Phase I/II study have provided the basis to conduct advanced clinical study in this indication.