At present a Phase II study in MS is ongoing “Safety, Tolerability and Activity Study of Ibudilast in Subjects With Progressive Multiple Sclerosis” (NCT01982942) Estimated completion = May 2107
ple sclerosis who are currently untreated with long-term MS disease modifying therapy (DMT) or who are receiving either glatiramer acetate (GA) or interferon beta (IFNβ-1a [Avonex, Rebif] or IFNβ-1b [Betaseron Etavia]) treatment. Study drug will be administered as an adjunct to glatiramer or beta interferon treatment. A total of 250 male and female subjects from 21 to 65 years old, inclusive, are planned to be enrolled into two treatment groups. Randomization of subjects will be stratified by disease status (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) and immunomodulating therapy status: current use of immunomodulating therapy or no current use of immunomodulating therapy.
According to the FDA, in order to be granted Fast Track designation, a drug must (1) be intended for the treatment of a serious or life-threatening disease or condition; and (2) demonstrate the potential to address unmet medical needs for the disease or condition.
- More frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval;
- Accelerated Approval, i.e., approval based on an effect on a surrogate, or substitute endpoint reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality;
- Priority Review, with an FDA goal for completing review within six months of submission; and
- Rolling Review, which means that a sponsor can submit completed sections of its New Drug Application (NDA) for review by the FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed.
Is this action occurring because the company making Ibudilast has been pushing for this to happen (I suspect so)……. or is it the trial because it is sponsored by the US Government (NIH) & the NMSS.
As for MS-SPRINT I suspect they will still need to do a phase III if this trial is positive. So access may not happen soon.
MS -SMART is a UK based trial originally intended to test Ibudilast, Amiloride and Riluzole in Secondary Progressive MS.
I first heard about Ibudilast when someone who had been trawling the patent data base brought this to my attention and wanted us to do some EAE work.
Because of the mechanism of action of Ibudilast and past experience.
Ibudilast is a phosphodiesterase 4 inhibitior….not viagra which is a phosphodiesterase 5 inhibitior.
So phosphodiesterase 4 inhibitors inhibit enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s).
I suspect TNF= good and TNF=bad also but it is context dependent and timing may be critical is what happens when.
However the ibudilast showed that it had no effect on relapses or lesion formation however unexpectedly there was a slowing of disability progression and less brain volume loss, indicating to me that it is neuroprotective. This is the basis for MS sprint. Hopefully there will not be any exacerbations but it there are, you heard it here first, and as people on the trials are on DMT this should be less likely.
It has also been reported that PDE4 inhibitors can promote remyelination
Now you may have missed out on MS-SPRINT, but if you live in the UK there is still time to get on MS-SMART where the trial is now looking at the effect of riluzole, amiloride or prozac.
If you fit the criteria please consider volunteering click here to find out more