Sanofi has announced that enrolment for international phase 3 trials assessing tolebrutinib as a treatment for multiple sclerosis (MS) have been paused. However, the company has confirmed that, despite the pause, US studies are still going ahead.
Tolebrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that can cross the blood-brain barrier and enter the central nervous system, hindering the autoimmune response that causes brain damage in MS.
The decision to pause enrolment in other countries apart the US comes after the US Food and Drug Administration (FDA) placed a partial clinical hold on phase 3 studies evaluating tolebrutinib because of an ordered investigation of a safety signal.
The company noted the trials assessing the use of tolebrutinib in relapsing forms of MS – GEMINI 1 and 2 – are fully recruited and that it is still aiming to apply for US regulatory approval in 2024.
Sanofi also stated that, although regulators outside the US gave the green light for other trials in MS and myasthenia gravis to continue – even after it added measures to decrease the recruitment of people with pre-existing liver risk factors – it had made the decision to halt worldwide enrolment. This decision was based on advice issued by its Independent Data Monitoring Committee.
Sanofi highlighted that the decision for a pause was not because of additional safety data and added that all patients who are already involved in the trials will continue to receive drug treatment.
The HERCULES trial in non-relapsing secondary progressive MS, the PERSEUS trial in primary progressive MS and the URSA trial in myasthenia gravis have all been affected by the decision to pause research efforts.
Sanofi’s head of R&D, John Reed, said: “Patient safety remains our top priority as we continue to investigate the impact of tolebrutinib on liver function during this recruitment pause.
“We remain confident in the future of tolebrutinib as a potentially transformative oral treatment option for people living with MS and are working closely with regulatory authorities in order to resume active recruitment within the fourth quarter of 2022.”
Sanofi aquired tolebrutinib in 2020, along with two other clinical-stage BTK inhibitors, when it purchased Principia Biopharma for $3.7bn.