We want to build a sandwich to tackle the many facets of multiple sclerosis that result in neuroaxonal loss. At the base of treatment pyramid, we need an anti-inflammatory onto which we want to add a neuroprotectant, i.e. the combination therapy strategy.
You need to protect damaged and vulnerable axons so that you can then remyelinate them or restore their function. We assume this makes sense, but still, we get push back from many in the field who are determined to still do monotherapy neuroprotective trials.
What is the point of protecting an axon, allowing it to be remyelinated and to recover function for it to be damaged again in the next round of inflammatory attack?
Barts-MS Dictum: It makes no biological sense to do monotherapy MS neuroprotective trials in the modern era.
With this in mind, we had a ‘brainstorming’ session last week and came up with a new neuroprotective trial design in primary progressive MS; it is called the OXO PPMS trial or ‘Add-on OXcarbazepine to Ocrelizumab in PPMS Study’.
Why PPMS? We feel that PPMS has a massive unmet need and that as ocrelizumab is now licensed as the only DMT in PPMS it makes an ideal platform therapy. We have chosen oxcarbazepine, a sodium channel blocker, as our add-on agent because we have pilot data (animal and clinical) showing it may work and it seems to be better tolerated than other sodium channel blockers. In an ideal world, we would want this study to be done with a new agent that has a long patent life, which would allow Pharma to invest in the necessary studies to get the drug licensed. But alas we can’t find a Pharma company with a new sodium channel blockers who would be interested in MS.
Raj Kapoor, David Baker and I have spent an extraordinary amount of time trying to get Big Pharma to buy into the add-on sodium channel blocker neuroprotection paradigm. Sadly none of the decision-makers has bought into the paradigm, yet. Just maybe with new data and the fact that all the low-hanging fruit on the MS tree has been picked they may change their minds.
Please note that neuroprotection is only a small part of the solution to worsening or progressive MS. To tackle this problem we need a lot more than neuroprotection, which is why we need to manage MS holistically.
To reiterate the philosophy of marginal gains “if you break down everything we can think of that goes into improving MS outcomes, and then improving it by 1%, we will get a significant increase when we put them all together. This also means avoiding things that make MS worse”. This is why anti-ageing strategies, in particular, lifestyle factors, need to be included in the longterm treatment strategy to manage MS.
What do you think of the OXO PPMS study? If you have PPMS would you volunteer for this study?
CoI: multiple