On February 20, 2018 Athenex (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the Phase II clinical study data for KX2-391 for the treatment of actinic keratosis was presented by Dr. Seth Forman of Forward Clinical Trials, Tampa, at the American Academy of Dermatology Annual Meeting on February 17, 2018 in San Diego, California (abstract ID 6134) (Press release, Athenex, FEB 20, 2018, View Source;p=RssLanding&cat=news&id=2333323 [SID1234524063]).
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Actinic keratosis is a common skin condition that is induced through ultra-violet light damage, resulting in patches of thick, scaly or crusty skin. Left untreated, the lesions have risk of progression to squamous cell carcinoma and consequently treatment by a dermatologist is recommended. Actinic keratosis is the most common pre-cancerous condition in dermatology and affects more than 55 million Americans. Actinic keratosis constitutes between 14-29% of dermatologist visits in the USA1.
KX2-391, also known as KX-01, is a first-in-class dual Src kinase and tubulin polymerization inhibitor being developed as a topical medicinal product for the treatment of actinic keratosis.
This Phase II clinical study aims to determine the activity, safety and pharmacokinetics of KX2-391 ointment 1% (5 days or 3 days) in adults with actinic keratosis on the face or scalp. This is an open-label, multicenter study conducted in adults who had 4-8 actinic keratosis lesions within a 25 cm2 area on the face or scalp. A cohort of subjects was given once daily application for 5 days and was assessed through Day 57 for actinic keratosis lesion counts, local skin reactions (LSRs), and adverse events (AEs). LSRs were scored on a scale of 0 to 4 (worst). A second cohort of 3-day treatment was enrolled after the 5-day treatment regimen demonstrated activity and safety.
A total of 168 patients were recruited (84 for each cohort) from 16 US clinical sites. Subjects were mostly white males, with a mean age of 68 years, skin type I to III and median baseline number of actinic keratosis lesions of 6 for the 5-day treatment cohort and 5 for the 3-day treatment cohort. The 5-day treatment cohort achieved a higher overall 100 percent clearance of actinic keratosis lesions at Day-57 (i.e. 8 weeks after the initiation of treatment) than the 3-day treatment cohort (43% vs. 32%). In the 5-day treatment cohort, 23 of 44 subjects (52%) with actinic keratosis on face and 13 of 40 (33%) on scalp attained 100 percent clearance at Day-57. LSRs were mild and mostly erythema, flaking/scaling, crusting and swelling with the majority of the LSRs scores of <2 and resolved rapidly. Only one subject scored 4 in erythema and flaking/scaling, which both resolved rapidly without concomitant medications. Erosions/ulcers and vesicles/pustules were observed in only 15% and 5% of subjects, respectively. No subjects scored ≥3 in erosions/ulcers/vesicles/pustules. Treatment related AEs were few and predominately mild transient application site pruritus, tenderness and pain. There were no treatment related serious AEs or discontinuations. Plasma levels of KX2-391 were low to undetectable.
Dr. Seth Forman, the presenting investigator for the Phase II study, commented, "This study demonstrated that KX2-391 ointment 1% is well tolerated and active as a field treatment of actinic keratosis of the face and the scalp with LSRs that are mostly mild and transient. KX2-391 ointment 1% daily for 5 consecutive days is currently being investigated in two Phase III placebo-controlled trials."
Dr. Rudolf Kwan, Athenex’s Chief Medical Officer, commented, "We are excited to see the excellent efficacy and safety profile of KX2-391 ointment 1% for the treatment of actinic keratosis. KX01 treatment may have the potential to change the paradigm of topical therapy for actinic keratosis."
Athenex and the FDA previously had an end of Phase II meeting regarding the program for the design of the Phase III studies. Two placebo-controlled Phase III studies, with a total target of 600 patients (300 patients for each study) were initiated on September 25, 2017 and the enrollment was completed rapidly ahead of an aggressive schedule. Athenex expects topline data of the Phase III studies to be available in the third quarter of 2018.
As previously announced on December 11, 2017, Athenex and Almirall, a leading skin-health focused global pharmaceutical company and one of the leaders in the field of actinic keratosis treatment, entered into a license agreement in which Athenex granted Almirall an exclusive license under the Athenex Intellectual Property to research, develop and commercialize KX2-391 in the United States of America and European countries, including Russia. Athenex will receive an upfront fee and near-term payments of up to USD $55 million, and additional indications milestones payment and a royalty payment starting at 15% based on annual net sales, with incremental increases in royalty rates with increased sales. Athenex retains certain co-promotion rights in the USA and retains the rights for other parts of the world including Canada, Central and South America, Japan, Asia and China, Australia and New Zealand, and Africa including South Africa. Almirall will employ its expertise to support the development in Europe and also to commercialize the product in the defined territories. Milestones were established to encourage the joint effort of Athenex and Almirall to develop additional indications and additional formulations.
Mr. Peter Guenter, Chief Executive Officer of Almirall, stated, "As one of the leaders of the medical treatment of actinic keratosis, we were excited by the potential profile of KX2-391, as demonstrated in this Phase II clinical study. We are also impressed by the Athenex team’s capabilities in drug development execution. We are pleased that the Athenex team has already completed the enrollment of the two Phase III studies of 600 patients in the USA. We are fully committed to this collaboration and will assist in the European development and registration strategy. We believe that KX2-391 has the potential to change the standard of care for actinic keratosis and look forward to combining our leadership abilities in the field with the drug development expertise of Athenex."
References
E. Stockfleth et al. Physician perceptions and experience of current treatment in actinic keratosis. JEADV 2015, 29, 298–306