While the treatment options for multiple sclerosis (MS) patients are growing each year with the approval of new agents, all of the currently marketed treatments only slow the disease progression and sometimes carry risks of severe side effects, such as liver failure or viral infections, says GlobalData.

According to research by the leading data and analytics company, new mechanisms of action (MoA) are in constant development, with some of the more innovative ones utilizing cell-based therapies. For instance, there is a range of cell therapies and gene-modified cell therapies in development—from discovery stage to Phase II clinical trials. Currently, six different cell therapies are in Phase II development.

Barbora Salcman, Neurology Analyst at GlobalData, comments: “While the current MS market offers efficient treatment options that can significantly reduce the relapse rate and disease progression, such as Tysabri or Gilenya, there are no available agents that can fully cure MS or at least reduce the relapse rate further, halting the progression of the disease. This situation could potentially be improved through the use of cell therapies.”

The broader goal of cell therapies is to restore homeostasis in MS patients by introducing modified or unmodified cells—mesenchymal stem cells, T-reg cells or tolerogenic antigen-presenting cells, among others—into a patient, in the hopes of inflammation reduction and neuron regeneration. While efficacy is crucial when evaluating pipeline cell therapy products, it is also important to consider side effects, as these will dictate patients’ behavior towards this novel treatment modality and secure the drugs’ positions on the market.

Salcman continues: “While newer small molecule and biologic disease-modifying therapies (DMTs) only carry risk of side effects such as flu-like symptoms or headache (for example Aubagio or Copaxone), DMTs like Tysabri or Tecfidera are associated with increased risk of progressive multifocal leukoencephalopathy, a rare viral brain infection.

“Thus far, cell therapies in development for MS have been found to be well tolerated by patients, with no severe side effects; examples can be seen in the results from the Phase II clinical trial for NeuroGenesis’s NG-01 (NCT02166021) or Phase I/II trials for Imstem Biotechnology’s IMS001 (NCT04956744) and Atara Biotherapeutic’s ATA-188 (NCT03283826). However, as cell therapies are mainly in early-stage clinical trials, there is no guarantee how useful they might be for wider populations of patients in later phase trials. For example, this trend can be seen for ATA-188.”

In the Phase I/II EMBOLD trial, ATA-188 failed to demonstrate any significant improvement in expanded disability status scale among progressive MS patients during an interim analysis conducted in July 2022. Atara Biotherapeutics announced the updated trial results in October 2022, showing the stabilization or easing of disability in most of the patients with nonactive, progressive forms of MS. These results highlight how volatile early clinical trials can be for cell therapy products and the many factors that can influence the journey of these products to market.

Currently, no drugs are in the Phase III development, the rest of the pipeline includes six agents in Phase II, four in Phase I, 28 in pre-clinical stage and two in discovery stage.