We have been beating the combination-therapy drum for so long now we have become bored with the concept. Every time we apply for grants to test the concept, be it with pharma or via other traditional funding routes, we get pushback. Either our targets are questioned or the concept of combination therapies is challenged based on the scientific principles underlying the combination being proposed. Then there is regulatory complexity of doing licensing combination trials that makes most Pharma companies put their heads in the sand.
It is obvious that if we want to achieve our aim of getting pwMS to old age so that they can age normally we are going to have to do more than simply tackle inflammation.
Oncologise is a neologism or new word
I propose oncologising multiple sclerosis and putting in place a national NHS-funded register as part of routine practice, similar to what happens with cancer patients so that everyone can participate in add-on trials of neuroprotectants, remyelination and neurorestoration therapies and any other add-on treatments that we think may work in MS. The latter can include dietary interventions, for example, intermittent-fasting or ketogenic diets.
Making the case for building a treatment sandwich or pyramid
If the NHS doesn’t fund this I would urge Roche and Biogen to do start with the two biggest blockbusters, i.e. ocrelizumab- and DMF-treated patients and to do this as an international initiative. The real-life trial platform could be run like the oncology platforms in that as soon as you find a combination that is better than the monotherapy (plus placebo) the combination then becomes the standard of care. We would have to implement this with more sensitive outcome measures, possibly brain volume loss, rather than the EDSS which has too many warts to survive much longer.
Do you think we can oncologise MS? Would you be interested in participating in add-on studies as proposed above? We have ten or more compounds that we could test right now.
The good news is that I have an ally who works in a large Pharma company who has been chewing the cud with me on this concept and is hopefully going to be able to sell it within his company. If he doesn’t do it I suspect another company may be tempted to take it on.
I gave a talk to general physicians at the Royal College of Physicians (RCP) yesterday afternoon telling them how we have transformed the management of MS. But have we really? To really transform the management of MS we need to cure the disease and then tackle the problem of post-inflammatory neurodegeneration or smouldering MS. The problem we have is that the wider MS community is not necessarily prepared to accept this position and the need for combination therapy add-on studies or the sequential therapy paradigm (induction-maintenance).
CoI: multiple