Merck KGaA has said that the US Food and Drug Administration (FDA) has placed a partial clinical hold on new patients receiving its multiple sclerosis (MS) drug candidate evobrutinib.
The hold specifically applies to patients who have been taking the drug for less than 70 days, the company said, adding that its phase 3 EVOLUTION clinical trial programme in relapsing MS will continue as planned as all patients are beyond the time threshold.
The FDA’s decision was based on laboratory results that suggested there were two cases of drug-induced liver injury during the phase 3 studies. Both patients had been asymptomatic and their liver enzymes had fully normalised after discontinuation of the study medication.
“Merck is working closely with the FDA to establish the best path forward for the benefit of patients in current and future trials with evobrutinib,” the company said in a statement, adding that it is assessing the potential contributory role of predisposing factors to the liver injury.
Evobrutinib is one of multiple Bruton’s tyrosine kinase (BTK) inhibitors being developed to slow the progression of MS, and is not the first to spark concerns over drug-induced liver injury.
A late-stage trial testing Sanofi’s rival candidate tolebrutinib was put on partial hold by the FDA in June last year following reports of liver injury. Months later, Biogen and InnoCare’s orelabrutinib received a similar notice.
Roche and Genentech’s phase 3 BTK candidate fenebrutinib has yet to be hit by any FDA restrictions.
MS is a disabling, unpredictable neurological disease in which the immune system attacks the protective myelin sheath that covers the nerves and disrupts communication between the brain and the rest of the body.
It is estimated that there are over 130,000 people living with the condition in the UK alone, with around 7,000 people newly diagnosed each year.
Earlier this month, recruitment began for a ‘revolutionary’ UK trial, which is assessing whether existing drugs can be repurposed to help slow the progression of the disease.
The multi-arm, multi-stage Octopus trial is currently testing two drugs which have shown the potential to help protect nerves, and the flexible design means that drugs can be introduced or dropped as results emerge.