Athenex Announces That Two Phase 3 Pivotal Efficacy Studies of KX2-391 in Actinic Keratosis Achieved Their Primary Endpoints

Athenex announced that both Phase 3 studies, KX-AK-003 and KX-AK-004, had achieved their primary endpoint of 100% clearance of actinic keratosis (AK) lesions at Day 57 within the face or scalp treatment areas, with each study achieving statistical significance (p<0.0001). Statistical significance (p<0.001) was achieved for both face and scalp subgroups as well.

These two double-blind, randomized, vehicle-controlled, studies were designed as pivotal Phase 3 efficacy and safety studies to support the registration of KX2-391 (or KX-01) as field therapy for AK of the face and scalp. The studies, each conducted at 31 centers in the USA, enrolled a total of 702 subjects. KX2-391, or vehicle ointment, was applied once daily for 5 days. In addition to the clinical activity of KX2-391, the local skin reaction (LSR) profile was within expectations, in line with the Phase 2 study reported in the annual American Academy of Dermatology (AAD) meeting in February 2018 in San Diego.

Following an End of Phase 2 meeting with the United States Food and Drug Administration (US FDA), these two parallel Phase 3 pivotal studies were initiated in September 2017. In February 2018, Athenex announced that the recruitment had been completed ahead of schedule. Both studies are still on-going to complete the one-year follow-up of the patients who had complete responses. Athenex will be submitting a request to the US FDA for a pre-NDA submission meeting to discuss the data and regulatory submission timelines. The Company plans to submit the topline and other related data from the Phase 3 studies for presentation at an upcoming scientific meeting.

Dr. Rudolf Kwan, Athenex’s Chief Medical Officer, said, “These two pivotal studies confirmed 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. The rapid recruitment of patients into the two Phase 3 studies underscores the enthusiasm of the clinical investigators in the potential of this novel medical treatment. The clinical studies results have been consistent between Phase 2 and the two Phase 3 studies, highlighting the consistency of this treatment in patients with actinic keratosis. We believe KX2-391 has the potential to change the paradigm of topical therapy for Actinic Keratosis.”

Dr. Johnson Lau, Athenex’s Chairman of the Board and Chief Executive Officer, commented, “Athenex would like to thank the preclinical team, the clinical team and the product development team for their significant contributions in driving the preclinical and clinical development. Athenex would also like to specifically thank the clinical investigators, who recruited patients at a rate that exceeded our expectations and contributed significantly to the advancement of the medical treatment of actinic keratosis, a condition which is considered to be pre-malignant. Athenex is currently conducting all the necessary studies and work to complete the follow up and prepare the regulatory filing. We are also working closely with our partner, Almirall, to develop the European registration plan. Athenex is also actively planning for the development of KX2-391 in other geographic areas.”

KX2-391, also known as KX-01, is a first-in-class dual Src kinase and tubulin polymerization inhibitor being developed by Athenex as a topical medicinal product (1% ointment) for the treatment of actinic keratosis in adult patients.

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, and account for between 14-29% of dermatologist visits in the USA.

A Phase 2 clinical study (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) was conducted in 16 US clinical sites comparing a 5 days vs. 3 days treatment (84 for each cohort) and was reported in the AAD meeting earlier this year. The 5-day treatment cohort achieved a higher overall 100% 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% 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.

As previously announced on December 11, 2017, Athenex, Inc., and Almirall, S.A., 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. Pursuant to the license agreement, there are 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 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 to see the successful results in both parallel Phase 3 studies. We were impressed by the Athenex team’s capabilities in drug development execution. The rapid recruitment in these two parallel clinical studies and the ahead of schedule analysis underscore the leadership of the clinical research team and the senior management of Athenex. We are fully committed to this collaboration and will be helping to lead the European development and registration strategy. KX2-391 has the potential to change the standard of care for Actinic Keratosis and we look forward to combining our leadership abilities in the field with the drug development expertise of Athenex to advance patient care.”

Athenex is also running another ongoing Phase 3 study on the use of Oraxol (an oral form of paclitaxel with a P-glycoprotein for enhancing oral absorption with preliminary data showing potentially better efficacy and safety profile compared to intravenous paclitaxel) and the second interim analysis results will be presented to the Data and Safety Monitoring Board (DSMB) in late third quarter 2018.