Brave New World: Oral Medicines in MS

In a few hours, the U.S. FDA (Food and Drug Administration) is set to make history by approving the first oral medication for the reduction of annualized relapse rate in Relapsing forms of MS.

It is unlikely that the FDA will delay this milestone in MS therapeutics, and so Novartis's FTY720 (Fingolimod) will be welcomed to our growing MS armamentarium. It is unclear what the name of this medication will be -- please see: http://bit.ly/aqTrsz (will Gilenia be spelled "Gelenia" or "Gelinia" or "Gelenea" or "Gelinea").

Of course predictions of how MS specialists and general neurologists will use this medication, are usually discussed in private consultations with Wall Street analysts/investors, but I thought that it would be useful to discuss different patient types and where FTY720 may be positioned in their care:

1. Clinically Isolated Syndrome (CIS) -- FTY720 has not been systematically studied in CIS, and so there will be no FDA indication for its use in the first demyelinating event suggestive of MS. In the future, however, FTY720 may be studied, just as EMD Serono's Cladribine is (ORACLE MS - Oral Cladribine in Early MS). Novartis will probably wait some time before initiating a large scale CIS trial, just as the other DMD companies did (CHAMPS, ETOMS, BENEFIT, PreCISe).

2. Early MS -- Patients and their physicians will weigh the benefits of an oral medication as well as the patients' desire to not be on injectable medications, against the long term safety data of the currently approved injectable MS treatments.

3. Newly diagnosed -- When faced with options of an oral medication or injectables/intravenous (IV) medications, patients may be swayed to choose the oral treatment because of fears concerning the older medications and a perception that oral means safer (this is not necessarily borne out by the safety data).

4. Active RRMS -- People with active inflammatory MS will need an additional option to control the demyelinating lesions, and FTY720 will afford another option. Patients and their neurologists will choose between Biogen Idec's and Elan's Tysabri (natalizumab) and FTY720. Other patients who have been on every DMD, will only have FTY720 to choose from.

5. MS patients who have not tolerated other MS medications -- FTY720 will allow an additional medication option for those who cannot be on the other DMDs because of tolerability issues.

6. Early secondary progressive MS -- Although not studied in TRANSFORMS or FREEDOMS, there is an ongoing trial of FTY720 in PPMS (primary progressive MS). If the suggestive animal data translates into human beings, then FTY720 could be effective in both RRMS and PPMS, which would make it an attractive drug for SPMS.

7. Later secondary progressive and primary progressive MS -- Although not studied in TRANSFORMS or FREEDOMS, there is an ongoing trial of FTY720 in PPMS (primary progressive MS). If the suggestive animal data translates into human beings, then FTY720 could be effective in PPMS (and perhaps later SPMS).

8. Patients in the FREEDOMS II trial -- Patients who are enrolled in the ongoing placebo-controlled trial of FTY720, may be tempted to drop out and initiate FTY720, instead of taking the risk of placebo. This drop-out rate plus the approval of FTY720 may cause the Data Safety Monitoring Board (DSMB) to cut FREEDOMS II short.

9. Patients in other MS clinical trials -- Patients may choose to start this new oral medication instead of taking the risk of placebo in other trials. This could have a chilling effect on ongoing MS research.

As you can see, there are many potential uses for FTY720, but most importantly it will be AVAILABLE.

- Dr. Daniel Kantor, MD BSE

Medical Director

Neurologique

info@neurologique.org

www.neurologique.org