HQ Team
April 13, 2023: Merck KGaA announced the USFDA had put a hold on the initiation of new patients to test its relapsing multiple sclerosis drug after it caused liver injuries.
The FDA has placed a “partial clinical hold” on the enrollment of new patients to test evobrutinib and patients with less than 70 days of exposure to the study medication in the US, according to a company statement.
The FDA assessed two recently reported cases that may have caused drug-induced liver injury during the phase III clinical studies.
Both patients were asymptomatic, did not require any medical intervention or hospitalization for this condition, and their liver enzymes fully normalized after discontinuing the study medication, according to the Merck statement.
The phase III trials will continue as all participants in treatment are beyond 70 days of exposure to the study medication.
Closely monitored
The phase III clinical trial program of evobrutinib will deliver its data in the fourth quarter of 2023. The German drugmaker didn’t give a timeline on when the company will get out of the “partial” FDA hold.
Since initiation, the phase III clinical trial program of evobrutinib has been closely monitored by an Independent Data Monitoring Committee, including hepatologists.
“In close collaboration with external experts and the Independent Data Monitoring Committee for the trials, Merck is assessing the potential contributory role of predisposing factors to liver injury.”
Merck is working closely with the FDA to find “the best path forward” for the benefit of patients in current and future trials with evobrutinib.
Evobrutinib, an oral drug penetrating the brain and spinal cord or central nervous system, is a highly selective inhibitor of Bruton’s tyrosine kinase (BTK).
The BTK inhibitor is regarded as a potential treatment for relapsing multiple sclerosis.
No approval
It is the first inhibitor to demonstrate clinical efficacy in the largest Phase II study with follow-up beyond three years. Evobrutinib is not approved for any use anywhere in the world.
Drug-induced liver injury has been the most frequent cause of safety-related drug marketing withdrawals for the past 50 years, according to an FDA statement.
Hepatotoxicity, or damage to the liver caused by a medicine, chemical, herbal or dietary supplement,
discovered after marketing approval also has limited the use of many drugs.
Several drugs have not been approved in the United States because European marketing experience revealed their hepatotoxicity.
Severe liver damage potential
Some drugs were not approved in the United States because pre-marketing experience provided evidence of the potential for severe liver injury.
Many drugs cause cholestasis, but in general, this condition is reversible after the administration of the offending drug has stopped.
Cholestasis is the slowing or stalling of bile flow through the biliary system. Bile that can’t flow leaks into your bloodstream and backs up into your organs, causing inflammation.
