Advertise With UsAdvertise on our extensive network of industry websites and newsletters.
Get the PBR newsletterSign up to our free email to get all the latest PBR
news.Xenon Pharmaceuticals has started a Phase 1 clinical trial of its lead program, XEN801, as a potential treatment for acne.
Subscribe to our email newsletter
The Clinical Trial Application (CTA) for XEN801 was accepted by Health Canada and the first patient has been dosed in the Phase 1 clinical trial.
If supported by positive data from the Phase 1 trial, the Company plans to initiate a proof-of-concept Phase 2 trial in patients with moderate-to-severe acne by the end of the year with data expected in 2016. XEN801 is a novel, topically administered, selective, small molecule inhibitor of stearyl Co-A desaturase (SCD1), an enzyme involved in lipid synthesis that is expressed in sebaceous glands in the skin.
Xenon president and CEO Simon Pimstone said: "Initiating clinical development of XEN801 is a major milestone in advancing Xenon’s proprietary pipeline. We believe that the dual mechanism SCD1 inhibitory activity of XEN801 may be especially promising in treating acne by targeting both the reduction of the size and number of sebaceous glands as well as sebum production.
In addition, because of the serious side effects that often limit the use of currently approved retinoid treatments, topically applied XEN801 may represent a novel and safer approach. As 2015 progresses, we intend to continue to advance our partnered and proprietary pipeline programs, and leverage the potential of our Extreme Genetics discovery platform and expertise in ion channel target discovery. We anticipate continued progress across our product candidate pipeline, and believe that its diversity in therapeutic indications and stages of development is a major strength."
About XEN801
XEN801 is a topically administered, selective, small molecule inhibitor of stearyl Co-A desaturase (SCD1), an enzyme involved in lipid synthesis that is expressed in sebaceous glands in the skin. Xenon believes that XEN801 can have an impact on acne via two distinct mechanisms – firstly, by reducing monounsaturated fatty acids to reduce the production of sebum lipids produced by sebaceous glands, and secondly, by inhibiting SCD1 and increasing the production of retinoic acid endogenously which can have an apoptotic effect on the cells of the sebaceous glands.
Xenon has tested this mechanism in human sebocyte cell lines, and demonstrated an ability to increase levels of neutrophil gelatinase-associated lipocalin, or NGAL, a protein that mediates sebocyte apoptosis (cell death). NGAL is increased through retinoic acid signaling. Xenon believes these data support a differentiated mechanism of XEN801 compared to other drugs that are approved or are in development for acne.
Phase 1 and Phase 2 Trial Designs
The Phase 1 clinical trial of XEN801 is designed to enroll up to 3 cohorts of 12 healthy subjects per cohort dosed in a 14-day or 21-day treatment period. The objectives of Phase 1 are to determine safety and tolerability as well as to determine XEN801’s systemic and skin exposure.
If supported by positive data from the Phase 1 trial, the Phase 2 clinical trial of XEN801 will evaluate the efficacy, safety, tolerability and systemic exposure of XEN801 in approximately 150 patients with moderate-to-severe facial acne. The trial is designed as a randomized, multi-center, double-blind, vehicle-controlled (topical gel without active pharmaceutical ingredient), parallel-group design. Subjects will apply XEN801 topically to their face for 12-weeks with a 4-week follow up.
The primary efficacy endpoint is the percent change in total (inflammatory and non-inflammatory) lesion count from baseline to week 12. Secondary endpoints include the percent change in inflammatory and/or non-inflammatory lesions at different time points throughout the 12 week study as well as a number of Investigator’s Global Assessment (IGAs) measures.
About Acne
Acne is a multifactorial disease of the pilosebaceous unit, which are skin structures consisting of a hair follicle and its associated sebaceous gland. Increased levels of androgens, such as testosterone, which occurs during puberty, cause an enlargement of the sebaceous gland that increases the amount of sebum, a naturally occurring oil, production. Acne develops as a result of blockages in the hair follicles due to the sebaceous glands becoming clogged with excess sebum and dead skin cells. Under these conditions, the bacteria proprionibacterium acnes can multiply and cause the noticeable inflammatory lesions.