Clinical pilot study
The safety and efficacy of T-Guard™ was evaluated in a clinical pilot study at the Radboud University Nijmegen Medical Centre in the Netherlands. The main objectives of this study were to determine the pharmacokinetics, to detect any serious side effects and to evaluate to what extent T-Guard eliminates the T cells responsible for causing GVHD. The encouraging results, showing T-Guard’s clear therapeutic window in the treatment of severe acute GVHD, and other details of the study were published in a leading scientific journal. This generated further interest in the product and contributed towards securing additional support for further research.
Phase 1b/2 study
At the end of 2016, Xenikos completed a 20 patient multi-center phase 1b/2 study. The results showed that T-Guard™ had a good safety and tolerability profile and very promising clinical efficacy.
In particular, a high Day 28 complete response rate, an important and commonly used surrogate endpoint for second-line acute GVHD studies, was observed. Additionally, there was a substantial increase in 6-month overall survival as compared to historical institutional controls and matched controls selected from an international database. The top-line study results will be presented at the 2017 ASH annual meeting in Atlanta, USA. Currently, a detailed manuscript is being prepared which will be submitted to a leading scientific paper.
Randomised active-controlled Phase 3 study
Encouraged by the positive Phase 1b/2 study, preparations for a randomized active-controlled pivotal study are ongoing. In this study, the safety and efficacy of T-Guard™ will be compared to the best available therapies. Several renowned EU and US transplant centers have already expressed their commitment to participate in this study.
The study is tentatively scheduled to start early 2018 and could result in conditional marketing authorization/accelerated approval.
Additional opportunities in GVHD
As an important next step, it is envisioned that T-Guard™ could be applied earlier in the course of the disease. There is an increasing number of biomarkers being developed and validated that can be used to identify acute GVHD patients who are at high risk of not responding to steroid treatment. For these patients, it would make sense to add T-Guard in combination with the first-line steroid treatment to prevent irreparable damage to the organs and immune system. Also in this setting, the short duration and targeted nature of T-Guard treatment could enable intervention at an early stage of the disease without inducing deep and long-term immunosuppression.
Based on the results observed to date, Xenikos believes that T-Guard™ has the potential to offer a curative approach using a single-week treatment. In contrast with concepts to improve the symptomatic treatment of patients, T-Guard aims to restore the immunological balance, providing a durable remedy for patients with this devastating and potentially lethal disease.