A multiple sclerosis (MS) patient treated in Germany with Ocrevus (ocrelizumab) has developed the dreaded brain infection progressive multifocal leukoencephalopathy (PML). But it is not clear whether the recently approved Genentech/Roche-developed treatment is the cause.
The patient took the last dose of a three-year course of Tysabri (natalizumab) in February. Tysabri is a known trigger of PML — a severe brain infection caused by the John Cunningham (JC) virus, which leaves the majority of patients severely disabled or causes their death.
In April, the patient received one dose of Ocrevus as part of a German compassionate-use program. The person has not been otherwise identified.
According to Anthony Vaughn, international communications leader, multiple sclerosis, at Roche, the company is investigating the case. An email statement he gave to Multiple Sclerosis News Today said the patient tested positive for JC virus infection, but did not specify if the testing was performed before or after the Ocrevus infusion.
The patient’s treating physician has reported the PML case as a carry-over from Tysabri, according to the Roche statement.
An opportunistic microbe, the PML-causing JC virus is not harmful to people with an intact immune response, but many MS treatments are immunosuppressive. Several therapies that target T-cells have been linked to PML. Ocrevus does not directly act on T-cells, but its close cousin Rituxan (rituximab) — which like Ocrevus targets CD20 B-cells — has also been associated with this aggressive brain disease.
No patient developed PML during Ocrevus’ extensive clinical trials. But this fact is no guarantee that the condition will not appear as more patients receive the treatment. PML is a rare complication, and was not discovered in Tysabri-treated patients until the drug gained market approval.
The prescription label of Ocrevus includes a note about a possible PML risk, but that warning is largely thought to be an FDA precaution. Tysabri’s label, in comparison, now includes a much stronger notice of risk, called a black-box warning.
Genentech and its parent company, Roche, have kept a close eye on this possibility, with several currently running clinical trials aiming to explore the long-term safety of Ocrevus.
“Patient safety is Roche’s highest priority and we are gathering more details about the case and the patient’s history. We will continue to share information with healthcare providers and global health authorities as we know more,” Roche said in its statement.