I wasn't able to find the FDA data describing the clinical trial results that I read before going on Gilenya. But here are two sources you might find useful. The claim is that some but not all aspects are suppressed and that immune surveillance is retained.
Good luck. Whatever you decide.
Excerpt from full text available journal article re study results
Full text available pubmed central
Discov Med. Author manuscript; available in PMC 2013 June 27.
Published in final edited form as:
Discov Med. 2011 September; 12(64): 213–228.
A Mechanistically Novel, First Oral Therapy for Multiple Sclerosis: The Development of Fingolimod (FTY720, Gilenya)
Jerold Chun, M.D., Ph.D. and Volker Brinkmann, Ph.D.
Fingolimod Immunological Activities
Two corollaries with particular relevance to MS through this differential effect of fingolimod on CCR7-positive
vs. CCR7-negative T cells may contribute to efficacy and safety, respectively. First, fingolimod may produce efficacy
by sequestering the CCR7-positive cells, which include naïve and central memory T cells,
the latter of which have a key role in immunological memory. Following antigen exposure,
central memory T lymphocytes can undergo clonal expansion and differentiation to generate
effectors/effector memory T cells which provide adaptive immunity against recognized antigens
(Iezzi et al., 2001; Sallusto et al., 2004). Central memory T cell retention by fingolimod
could function as a therapy in MS since more than 90% of T cells that are found in the cerebrospinal fluid (CSF)
appear to be of the central memory subset (Kivisakk et al., 2004).
The contained autoreactive, pathological T cells could therefore be prevented from entering the CNS
by fingolimod sequestration, thereby abrogating their differentiation into pathological effectors and
effector memory T cells upon interaction with CNS-resident antigen-presenting dendritic cells.
In animal models, fingolimod prevented accumulation of pathological Th17 cells in the nervous system
(Zhang et al., 2008; 2009), supporting Th17 cell- or Th17 cell precursor sequestration as an efficacy mechanism.
Accordingly, phenotypic Th17 cells were reduced in the circulation in fingolimod-treated MS patients
(Mehling et al., 2010). In addition to efficacy by CCR7-positive cell sequestration of pathological T cells,
fingolimod could provide safety through maintained immunosurveillance. Such functionality would be
produced by preferentially not affecting CCR7-negative effector memory T cells of any functional phenotypes
In support of the above, another study proposed that Gαi2 null T cells egress independent of S1P-mediated chemotaxis
(Zhi et al., 2011), and these cells were also not retained by fingolimod. Intravital imaging of lymph nodes revealed
that T cells approach and engage cortical sinusoids in lymph nodes similarly in the presence or absence of fingolimod.
However, after engagement of the sinus, most T cells retract and migrate back into the parenchyma in fingolimod-treated
animals, due to a failure of the cells to establish adhesion on the sinus, whereas Gαi2-deficient T cells adhere firmly
on the sinus, which prevents their retraction, facilitating their transmigration of the lymphatic endothelial barrier.
Interestingly, Gαi2-deficient T lymphocytes are hyper-responsive for T cell receptor signaling and cytokine production,
with a relaxed costimulatory requirement (Huang et al., 2003) — a phenotype matching effector memory T cells — again
supporting sparing of this subset by fingolimod.
Immunomodulatory Approaches to MS Therapy
A notable corollary of the dual immunological and CNS fingolimod mechanisms is that fingolimod does not fit
the profile of an immunosuppressive agent like those in common use in the transplantation field - e.g.,
“classical” immunosuppressive agents like calcineurin inhibitors [Cyclosporine, Tacrolimus
(Borel and Kis, 1991; Juhasz et al., 2009; Stahelin, 1996)], high dose corticosteroids [e.g., Prednisone (Goetzl, 2008)]
, and cytotoxic and/or antimitotic agents [azathioprine, mycophenolate, or cladribine (Goetzl, 2008; Neuhaus et al., 2007)]
or biologicals, including a growing number of humanized antibodies raised against immune cell targets [CD3, IL-2 receptor,
integrins, CD52 (Buttmann, 2010; Nitta et al., 1992; Steinman, 2005; Wolff et al., 2004)].
Early approaches to the treatment of MS utilized classical immunosuppressive strategies, some of which continue to be used
today (Neuhaus et al., 2007). However, risk of serious neoplastic and/or infectious adverse events limits their use.
This issue has been underscored by the rare occurrence of progressive multifocal leukoencephalopathy (PML) associated
with the use of natalizumab or rituximab (Buttmann, 2010). T cell immunosuppression may be involved in both cases;
in addition to its effects on T cell trafficking, natalizumab may interfere with the VLA4-VCAM1 costimulatory pathway
that is critical to human CD4 T cell proliferation (Weitz-Schmidt et al., 2001), and therapeutic B cell depletion by
rituximab was shown to impair B cell antigen-presentation and, as a consequence, CD4 T cell activation and clonal expansion
in response to pathogen challenge (Bouaziz et al., 2007). Therefore, the sparing of effector memory T cells in both CD4
and CD8 populations by fingolimod could be critical to immunosurveillance; in the meninges of mice, fingolimod
preferentially reduced naive and central memory T cells, whereas anti-VLA4 treatment primarily depleted the effector
memory population (Derecki et al., 2010) (see also above for the key role of circulating central memory T cells in
pathology of MS).
The above data support the notion that fingolimod at its approved dose may not act as a potent immunosuppressant:
1) CNS effects are unrelated to immunosuppression; 2) suboptimal prevention of graft rejection was achieved
in renal transplantation studies in combination with cyclosporine, despite being at 10X the approved MS dose;
3) immunological constituents are maintained (cellular and humoral), with reversible effects on cell location of some
(but not all) lymphocyte subsets —without inhibition of proliferation, differentiation, and cytotoxicity;
4) immunological surveillance is maintained through relatively unaffected effector memory T-cells; and
5) clinically, the overall incidence of infections as well as of serious and severe infections was not
increased over placebo control in the FREEDOMS trial in phase III studies. Overall, the emerging picture
identifies S1P receptor pathways in MS that can provide efficacy through mechanisms different from classical
Collectively, the data show that activation and proliferation of naïve and central memory T-cells, as well as
differentiation and trafficking of effector memory T-cells, may not be significantly affected by fingolimod,
thereby preserving this arm of the adaptive immune system that can reduce the risk of infection and cancers
common with immunosuppressive agents. Consistent with this mechanism, the combined data from both
aforementioned Phase III trials did not suggest an increased incidence of either infections or malignancies
associated with fingolimod treatment (Cohen et al., 2010; Kappos et al., 2010).
(Mehling et al., 2008), which may leave lymph nodes, independent of S1P1 signaling (Pham et al., 2008).
Excerpt from Health Canadahttp://www.hc-sc.gc.ca/dhp-mps/prodphar ... 16-eng.php
Health Canada Summary Basis of Decision (SBD) for PrGILENYA*
Gilenya* induced a rapid decline in peripheral blood lymphocyte counts within the first few hours of dose administration,
with counts reduced to 50% of the baseline values after 8 hours. With chronic daily dosing lymphocyte counts continued
to decrease over the first two weeks and reached a low point (~0.5 x 109/L) that is approximately 30% of baseline values.
In the clinical studies, lymphocyte counts below 0.2 x 109/L were considered clinically notable values, for which
treatment interruption was to be considered. These values were reached at least once in the two-year study (D2301)
by 18% of patients administered 0.5 mg Gilenya* and 4% of patients administered 0.5 mg Gilenya* had lymphocyte counts
below 0.2 x 109/L for at least 180 days. A complete blood cell count should be obtained before initiating treatment
to ensure a patient is not lymphopenic, and may be checked during an active infection. Recovery of lymphocyte counts
to baseline levels typically takes approximately two months following treatment discontinuation, during which time
the immune effects may still be present and the patient at an increased risk for infections. During this time,
initiating treatment with other immunosuppressive therapies would warrant extreme caution.