My take on some MS therapies in advanced development:
BG12 (oral fumarate ) and Laquinamod have low efficacy and low side effects. Will be primarily targeting early patients (CIS) and those not willing to tolerate side effects of the more efficacious drugs. BG12 apparantly has a combination of cytoprotective and anti-inflammatory properties (suppress peripheral CD4 and CD8-positive lymphocytes and may also cause Th1 lymphocytes shift to Th2).
FTY720 (a sphingosine-1-phosphate receptor modulator), looks good. The side effects in phase II are worrying BUT, I think that the Tysabri experience made physicians and patients more comfortable with side effects.
Oral Cladribine (a purine nucleoside analogue with preferential lymphocyte-depleting properties), which is an approved therapy for hairy cell leukaemia and lymphoma, will probably be the first of the new oral drugs on the market. It has decent odds of gaining some traction. Results from previous phase II and III trials in MS using an injectable formulation came close to hitting several of its endpoints, boding well for the oral formulation. It was safe, well tolerated and reduced the number, and volume, of lesions. However, there was no effect on EDSS.
Campath needs to prove monthly monitoring by blood test can overcome ITP risk. It is by far the most efficacious drug and despite severe side effects (who needs CD4+ cells?), in most cases ITP is reversible.
Rituxan - there is growing scientific rationale in support of the efficacy of B-cell depletion therapy for MS (also goes to ocrelizumab). Rituxan's safety profile in chronic autoimmune disorders is supported by growing long-term experience in RA.
Teriflunomide is an approved treatment for RA. It inhibits T-cell activation. In a phase II MS study, it was shown to significantly decrease T1-contrast enhancing and new T2 lesions on MRI scans and a trend for fewer relapses was seen. It was also well tolerated and adverse events were similar across groups. I suppose it can be one of the low efficacy/low AE drugs.
MBP8298 for MS patients with HLA types DR2 and/or DR4, is worth mentioning because of lack of trials in SPMS.
Some of these drugs will get through despite the side effects. Until a new drug gets to the market at 2012 or so, I think it is clear that interferons are in decline and Copaxone will gain from this and from Tysabri's safety problems.
Btw, most of these candidates are being tested in placebo controlled trials which are slow and competitive and have difficult time in completing enrollment. Also much more mild patients are recruiting and that reduce the power of the trial and could make it harder to show effect.
