A clinically significant risk of injury was reported with CENRIFKI (tolebrutinib)^¹

Pooled liver safety^1-3*

• CENRIFKI is contraindicated in patients with moderate to severe hepatic impairment¹
• Clinically significant liver injury, including acute liver failure resulting in/leading to transplant and/or death, has been reported in patients treated with CENRIFKl¹
• Liver injury is detectable with liver enzyme monitoring and generally reversible with discontinuation of CENRIFKl¹
• In the clinical trials, all cases of serious liver injury occurred within the first 3 months of starting CENRIFKI. All but 1 of the cases resolved without long-term effects after permanent discontinuation¹
• One liver injury led to transplant and death of a trial participant treated with CENRIFKl¹
  • This occurred prior to the implementation of a revised protocol with more frequent liver monitoring^1,4

The safety profile of CENRIFKI was studied in one of the largest MS clinical trial programs (N=2999)¹

*Among the 1685 patients treated with CENRIFKI, 0.2% had ALT elevations >3x ULN with concurrent bilirubin increases >2x ULN.¹

†Cases of peak ALT >20x ULN were observed at a higher rate in CENRIFKI (0.5%) vs placebo (0%), based on the nrSPMS Phase 3 clinical trial. Cases of peak ALT >20x ULN were observed at a higher rate in CENRIFKI (0.5%) vs teriflunomide (0.1%), based on two Phase 3 RMS clinical trials. Liver enzyme elevations (ALT >3x ULN) were observed at a higher frequency in CENRIFKI (4.1%) vs placebo (1.6%) based on an nrSPMS Phase 3 clinical trial. Liver enzyme elevations (ALT >3x ULN) were observed in CENRIFKI (5.6%) at a similar rate to teriflunomide (6.3%), based on two Phase 3 RMS clinical trials.^4,5

AE=adverse event; ALP=alkaline phosphatase; ALT=alanine transaminase; AST=aspartate aminotransferase; MS=multiple sclerosis; nrSPMS=non-relapsing secondary progressive multiple sclerosis; RMS=relapsing multiple sclerosis; TEAE=treatment-emergent adverse event; ULN=upper limit of normal.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side affects you may get.