WC500185968

Taking into account this first report of asymptomatic case of PML after long-term treatment with
fingolimod without prior immunosuppressive treatment and considering the seriousness of PML, the
PRAC agreed that a direct healthcare professional communication (DHPC) should be circulated
promptly and additional information on this signal is requested from the MAH. The PRAC also
considered that seeking expert advice from the Scientific Advisory Group (SAG) Neurology would be
helpful.
Summary of recommendation(s)
The PRAC agreed that the MAH for Gilenya (fingolimod) should distribute a DHPC according to
the text and communication plan agreed with the PRAC and CHMP.
The MAH for Gilenya should provide,by 06/04/2015 an estimate of total patient exposure (i.e.
from both trials and non-study use) stratified by duration of exposure to fingolimod along with
an estimate of the risk of PML according to the number of patients at risk, assuming that PML
associated with fingolimod has a long latency period of at least several years (over four years
in the index case).
The MAH should provide any new follow-up information on the case as soon as this is available,
especially confirmation of whether or not there was an immune reconstitution inflammatory
syndrome (IRIS)-type response in this patient after fingolimod withdrawal and whether or not
the MRI lesions are receding. The MAH should discuss the absence of overt clinical symptoms
in this case.
In addition, the MAH should discuss whether studies FTY20D2403 and FTY20D2406 are of
sufficient duration and size to adequately characterise the risk of PML with long-term
fingolimod therapy, especially when the index case had a time to onset of more than four
years.
The MAH should provide an updated cumulative review of data from all sources (including
previous cases) with the view of elucidating the mechanisms of action in relation to the risk of
PML for fingolimod, including any identifiable or potential risk factors (with and without prior
immunosuppressant treatments) that could inform implementation of risk minimisation
measures, or that would warrant further study.
A 30-day timetable was recommended for the assessment of this review leading to a further
PRAC recommendation.
4.2.5. Palifermin - KEPIVANCE (CAP)
Signal of increased mortality associated with unlicensed use in acute lung injury
Regulatory details:
PRAC Rapporteur: Rafe Suvarna (UK)
Administrative details:
EPITT 18160 – New signal
MAH(s): Swedish Orphan Biovitrum AB (publ)
Lead MS: UK
Background
Palifermin is a human keratinocyte growth factor (KGF) indicated to decrease the incidence, duration
and severity of oral mucositis in adult patients with haematological malignancies under certain
conditions.
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 19/89