Genentech Adds Warnings to Ocrevus Label

Genentech has updated the warnings section of the label for the MS therapy Ocrevus to include information about cases of immune-mediated colitis and a serious brain infection in the post-marketing setting.

Genentech has updated the warnings section on the Ocrevus (ocrelizumab) and added a new subsection about the risk of progressive multifocal leukoencephalopathy (PML), an infection of the brain caused by a virus targets the cells that make myelin.

Ocrevus is a monoclonal antibody that treats adult patients with relapsing forms of multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS). It targets the CD20-positive B immune cell that plays a key role in the disease.

A Genentech spokesperson said the label originally included a warning and precaution regarding progressive multifocal leukoencephalopathy in the context of other anti-CD20 antibodies and other multiple sclerosis (MS) therapies. “We have worked with the FDA to elevate the subsection on PML under infections to a separate warning stating that cases of PML have been reported in Ocrevus-treated patients in the post-marketing setting as a new warning and precaution,” she said.

Following FDA approval for Ocrevus in March 2017, 12 confirmed cases of PML have been reported among more than 250,000 people with MS who have been treated globally. Ten of the cases were carry-over cases of patients from a prior disease-modifying treatment (DMT) known to be causally associated with PML. There were two additional non-carry-over cases that were not related to a prior DMT or known medical condition, according to the spokesperson.

Additionally, Genentech has worked with the FDA to include new safety information in the U.S. prescribing information for Ocrevus by adding a new Warning and Precaution on immune-mediated colitis (IMC). Cases of inflammatory colitis including IMC have been reported without obvious contributory risk factors or alternate explanations.

“Patient safety is Genentech’s highest priority, and we share information with healthcare providers and regulators on an ongoing basis, in accordance with standard pharmacovigilance reporting,” the spokesperson said.

The added section in the Warnings and Precautions on PML now reads:

“Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with Ocrevus in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in Ocrevus-treated patients who had not been treated previously with natalizumab (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications associated with the risk of PML prior to or concomitantly with Ocrevus, and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.

JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

At the first sign or symptom suggestive of PML, withhold Ocrevus and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis.

It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients.”

The added section on colitis reads:

“Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving Ocrevus in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years. Monitor patients for immune-mediated colitis during Ocrevus treatment, and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.”