PML Dedicated Clinical Data Collection: An Industry Perspective

Background: In 2004, the US FDA approved natalizumab to treat patients with relapsing forms of MS. Shortly thereafter, reports of progressive multifocal leukoencephalopathy (PML) arose from long-term clinical trial patients, and Biogen voluntarily withdrew natalizumab from the market in 2005. Additional clinical data were gathered, and, in 2006, the product was reintroduced to the market with a risk minimization plan. Since this time, Biogen established a dedicated team to investigate and evaluate global PML reports. Information from adverse event reporting is crucial to allow risk assessments and inform risk minimization measures to protect the public's health and safety.

Objectives: To collect key PML clinical case data so that Biogen can assess and inform prescribers and stakeholders of the relevant risk of natalizumab-associated PML.

Methods: During PML suspicion/evaluation, Biogen offers resources to physicians to facilitate their diagnostic process. Upon receiving key clinical data, Biogen’s dedicated team, in collaboration with Biogen safety physicians, confirms or rules out a PML diagnosis using spinal fluid test results, radiologic evidence, and/or brain biopsy results. Following confirmation of a PML diagnosis, longitudinal data (up to 24 months) are requested to ascertain patient status and ongoing clinical course. These data are entered into the global safety database and a custom application to record and manage PML clinical data.

Results: Biogen has confirmed 698 cases of PML, with mean natalizumab treatment duration of 48 months. Biogen has informed physician practice by defining important PML risk factors. Specific clinical data obtained include anti-JCV antibody index values (present in 38% of cases) and 24-month longitudinal follow-up (present in 64% of cases). Biogen has also identified areas for further study, including JCV granule cell neuronopathy, asymptomatic PML, and MRI monitoring frequency.

Conclusions: Over the past 10 years, Biogen has proactively collected detailed patient data to inform natalizumab-associated PML risk. In close collaboration with global healthcare providers and patients, the compiled key clinical data have informed patient management as described in the natalizumab prescribing information and in scientific publications. We are grateful for the support of healthcare providers and look forward to continued collaboration and engagement to further improve collection of this key scientific data.