Roche is investigating one case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis (MS) after treatment with ocrelizumab (Ocrevus).
The Roche said that according to the treating physician, the case is a “carryover” from treatment with natalizumab (Tysabri, Biogen), which is known to be associated with PML. It reports that the patient, who was JC virus (JCV) positive, had been treated with natalizumab for 3 years, with the last infusion in February 2017.
The patient then received one dose of ocrelizumab in April 2017 on the compassionate use program in Germany
“Patient safety is Roche’s highest priority and we are gathering more details about the case and the patient’s history,” the company told Medscape Medical News. “We will continue to share information with healthcare providers and global health authorities as we know more.”
Ocrelizumab was approved in the United States in March this year for the treatment of both relapsing-remitting and primary progressive forms of MS. According to the drug’s prescribing information, there were no cases of PML in clinical trials of the drug.
A Biogen spokesperson confirmed the details of the case that Roche had given but said the company “cannot comment further on the specifics of this case, and we are currently assessing the information to confirm the reported PML. It is unknown if this case is a result of prior Tysabri use only.”
The Biogen drug carries a black box warning for PML risk, with patients reported to be at increased risk of developing the condition if they have been treated with natalizumab for more than 2 years, had received prior immunosuppressant therapy, and are JCV positive. The label says the estimated incidence of PML in the United States is 13 per 1000 patients with all three risk factors.
“This case is not surprising, as clinical evidence of PML may be subtle and slow to develop,” said Edward J. Fox, MD, MS Clinic of Central Texas, Round Rock, commenting on the case for Medscape Medical News. “Those patients currently on natalizumab with risk factors will be at risk for PML for several months after discontinuation of the drug, no matter what the next agent used might be. So, this is similar to other cases in the past with PML diagnosed following the transition of natalizumab to another agent.
“I don’t think that this should markedly affect the risk:benefit assessment of ocrelizumab, as the FDA approval included wording about the potential complication of PML,” Dr Fox noted. “After more thorough information is available about this first reported case, it will likely be attributed primarily to prior natalizumab use. Ongoing monitoring and reporting will be needed to properly determine the true risk of PML in patients treated long-term with ocrelizumab.”
Also commenting for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic, Ohio, said, “From the details I’ve seen it is not yet clear whether PML had already developed while the patient was on natalizumab or it developed de novo after ocrelizumab was administered. In either case, prior natalizumab probably increased the risk of PML.”
“So, this occurrence is not unexpected, but it illustrates somewhat of a dilemma,” he added. “One situation where I expect ocrelizumab will be considered is patients with highly active MS that is well controlled on natalizumab but who are JCV seropositive.”
Source: Medscape Medical News