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Progressive multifocal leukoencephalopathy

Three cases of confirmed PML have been reported in patients exposed to siponimod: one case in the siponimod development program (Extension part of phase 3 study [EXPAND)1]) and two cases in the post-marketing setting. One of these reported post-marketing PML cases is attributed to prior natalizumab treatment2, and the other to siponimod treatment3.

PML has been reported with other S1P receptor modulators and other MS therapies. Therefore, vigilance on the part of physicians and patients for signs and symptoms of infections is important while on therapy with siponimod and for up to 1 month after cessation of treatment4

Clinical and postmarketing_PML_v1

** cutoff date March 25, 2023
^ cutoff date March 25,2023


About PML

PML background

  • PML is caused by reactivation of the JC virus, a ubiquitous human papovavirus that is typically acquired during childhood and remains latent in the kidneys and possibly other sites (eg., mononuclear cells, CNS)4
  • PML is increasingly occurring as a complication of immunomodulatory therapy4
  • Common symptoms/signs include clumsiness, hemiparesis, aphasia, dysarthria, hemianopia, and cognitive impairment4
  • PML is suspected in patients with unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity4
  • CSF is analyzed for JC viral DNA using PCR; a positive result with compatible neuroimaging findings is nearly pathognomonic4
  • Supportive management and management of underlying disorders are helpful in managing PML4

Suspected or confirmed PML: Get Novartis support

Novartis support

Novartis can help physicians with the assessment of a suspected PML case, after the adverse event has been reported to the company via standard pharmacovigilance processes

  • Subsequently, there is access to an external expert MRI service and Novartis has constituted an external PML adjudication panel consisting of experts in the field for case evaluation
  • If a second opinion on an MRI with atypical findings/suspicion of PML is requested, Novartis can support obtaining this through an MRI expert center (Medical Image Analysis Centre [MIAC]), University Hospital Basel, Switzerland. Novartis will not have access to the MRI and will only receive a report
  • In addition, Novartis can support logistics for shipment of CSF samples for testing for presence of JC DNA (PCR) by Unilabs A/S, Denmark and by Quest in the US. In this case, both the physician and Novartis receives the report
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Last updated: November 2023. The page will be updated annually.

CNS, central nervous system; CSF, cerebrospinal fluid; JC, John Cunningham; MS, multiple sclerosis; MRI, Magnetic resonance imaging; PCR, polymerase chain reaction; PML, progressive multifocal leukoencephalopathy; S1P, sphingosine 1-phosphate receptor modulator

1. Data on File, cutoff date October 29, 2021 Novartis Pharma AG.
2. Data on FilePSUR, cutoff date 25-March-2023, Novartis Pharma AG
3. Data on file, cutoff date September 30,2023, Novartis Pharma AG.
4. Greenlee JE. Progressive Multifocal Leukoencephalopathy (PML). MSD Manual Professional Version. Accessed June 29, 2021.
* Indication varies in different countries. Current website is a global information resource. Local Prescribing Information/ Summary of Product Characteristics approved by individual country’s regulatory authority is the primary source of information for the indication of siponimod in the individual country.

The Pregnancy outcome Intensive Monitoring (PRIM) program is based on enhanced pharmacovigilance of the Novartis spontaneous reporting system. PRIM is an adverse event outcomes intensive monitoring program to collect information (targeted follow-up checklists) about pregnancy in patients exposed to siponimod immediately before or during pregnancy and infant outcomes 12 months after delivery.