syneoshealth.com
An exploration of the emerging issues for autoimmune drug developers in translating oncological adoptive cell therapy experience into autoimmune trials.
By Abhi Gupta, Kendra Keogh, James Barwick-Silk and Manfred Lauth
Adoptive cell therapies have transitioned from experimental concepts to commercialized products, particularly in the field of hematological malignancies. These therapies involve harnessing the power of a patient’s own immune cells to combat diseases. Developers are now directing their efforts toward autoimmune conditions, including chimeric antigen receptor T cells (CAR-Ts), Tregs (regulatory T cells), and T cell receptor-engineered T cells (TCR-T). These treatments have the remarkable ability to modify the immune system’s response resulting in potentially curative treatment options — and thereby giving hope to patients, caregivers and physicians.
Notably, the Bavarian Cancer Research Institute has reported compelling data in adoptive cell therapies: 15 patients with lupus and other autoimmune disorders, treated with CD19 CAR-T, are experiencing lasting remission. Encouraged by these results, several companies are actively exploring this therapeutic avenue. Ongoing studies are underway or planned for conditions such as type 1 diabetes (T1D), Crohn’s disease, multiple sclerosis and Alzheimer’s disease.
The following is an exploration of the emerging issues that are particularly challenging for autoimmune drug developers based on our deep expertise of translating our oncological adoptive cell therapy experience into autoimmune trials. We share three critical success factors, biopharmaceutical companies should consider as they move forward: benefit-risk profile education, translation and integration of adoptive cell therapy experience and capabilities and site staff training of specific cell therapeutic treatment options.
Research Science Liaisons (RSLs) should engage frequently with PIs, sites and patients to educate them on the benefit-risk profile of new therapies
While several principal investigators (PIs) and key opinion leaders (KOLs) are pioneering these emerging therapies, significant hesitancy from large parts of the community remains, due to the perceived and actual risk of using these novel therapy types. For example, treatments that require myeloablative regimens are particularly new to physicians treating autoimmune conditions. To mitigate that risk that this uncertainty brings including its impact on development timelines, medical and operational communication must be translated from asset developers to PIs and KOLs.
Direct interaction between sponsors/CROs and PIs is particularly critical during early development (pre-clinical / phase 1) to quickly solve emerging challenges, however this approach is not scalable as the number of sites, patients and other stakeholders evolves.
To scale medical communications we strongly recommend the deployment of on-the-ground research science liaisons (RSLs) to engage PIs and sites, understand their needs, communicate the scientific and medical requirements, build enthusiasm for the study and ultimately accelerate trial recruitment. The experience of on-the-ground RSLs will also be translated into patient engagement channels including potential patient forums, communication materials and study branding.
Taking this approach future proofs development, as RSLs optimize their approach for a therapy/indication’s specific needs, translating this practice into larger clinical trials and medical science liaison (MSL) engagements as commercialization approaches.
Translate and integrate adoptive cell therapy experience and capabilities from oncology trials to ensure timely delivery
Treatment using Adoptive Cell Therapies represents a different treatment paradigm for sites, requiring specific operational capabilities including: storage and administration equipment; institutional biosafety review (for gene modified therapies) and requirement for long-term follow-up safety of patients.
The sites most prepared for these therapies are those that have previously administered adoptive cell therapies in an oncology setting, enabling direct translations of capabilities between teams (e.g. translation of experience of using myeloablative regimens, administration & storage equipment).
To accelerate and help mediate the translation of these capabilities, we recommend employing operational teams that are directly engaged with internal oncology adoptive cell therapy teams and medical monitors to quickly resolve operational and medical challenge encountered in previous oncology studies.
Train site staff and familiarize them with the specifics of cell therapeutic treatment options
Ensuring that all site staff understand how to de-risk execution of these operationally complex trials is a critical success factor in any adoptive cell therapy trial.The content should pull directly from experts that understand the nuances of delivering these clinical trials, focusing and linking the science of cell therapies to the operational requirements. Typically, this content should cover:
Successful development in autoimmune conditions is centered around integrating and sharing knowledge between indication specialists and those that understand adoptive cell therapy.
Without careful curation, communication and education using this knowledge, key stakeholders will not engage in developing these therapies, ultimately putting the patient benefits of these potentially game-changing therapeutics at risk.
Is your team looking to bring its adoptive cell therapies to the next level? Explore what our immunology experts are doing in cell and gene therapy.
Abhi Gupta| Senior Vice President, Head of Cell and Gene Therapy
Kendra Keogh| Vice President, Therapeutic Strategy and Innovation
James Barwick-Silk, DPhil | Senior Director, Cell and Gene Therapy
Manfred Lauth, MD, PHD | Vice President, Therapeutic Strategy and Innovation