BYM338 – no answers yet

Yesterday I was back at The Leonard Wolfson Research Centre for another infusion of BYM338.  This month the news broke on the internet that the drug trial hasn’t achieved its ‘primary endpoint’ – the expected improvement in walking distance over 6 minutes hasn’t been met.  We don’t know what this means – whether there was some improvement overall but not as much as they’d forecast, or whether nobody has improved at all – we’ll just have to wait until more information is released.  The trial centres haven’t received any information other than that, and they heard that by email on the same day that the financial publications were running the story.  Bit naughty really.

When the news hit the internet, I found it completely unsettling and it made me question everything that I thought and felt about the drug.  In one way though, it was a bit of a relief because I’d wondered why I hadn’t really been able to improve my walking ability and thought perhaps I wasn’t trying hard enough, wasn’t exercising enough, or perhaps my body wasn’t reacting to the drug the way it was supposed to.  There was no need to worry about any of that any more, because obviously it wasn’t just me.  On the other hand though,  it made me wonder whether the other improvements I’d noticed were real or imagined, or whether they were only because of the exercises we’ve been doing.  Then I remembered that some of the trial participants are exercising just as regularly as I am, and not getting any results at all – they just continued to get weaker so they have probably been on the placebo, or a very low dose.   So the drug has to be doing something, doesn’t it?  The thought of the trial being cancelled fills me with horror, partly because I remember how quickly I lost strength when we had a 3 month break in treatment over the winter, and partly because that would mean that the drug won’t ever be licenced for IBM and none of the people who have been waiting for it to be available, encouraged by my progress to hope that they too will benefit one day, will be able to try it for themselves.  That would be so disappointing, to say the least.

The trial investigators have still got data to analyse though – they have got to look at the results of the pinch test, grip test and leg strength tests, as well as the indisputable evidence provided by the DEXA scans (showing any increase in muscle mass quite clearly, if present) and the questionnaires we fill in about what we can and can’t do.  If just one of those data sets shows any sort of improvement at all, then surely it is a worthwhile treatment regardless of the walking results.  After all, many of us can’t walk at all, but these patients would still benefit enormously from stronger breathing or swallowing muscles, stronger and more mobile fingers, hands and arms….  it’s not all about walking is it?

So all we can do is wait and see how it all turns out.  I think relying on the results of the 6 minute walk tests would be ridiculous.  Those of us who have dealt with IBM for several years  are not naturally fast walkers, we’re CAREFUL walkers, and I wasn’t convinced that an increase in strength would necessarily make us walk faster.  I’m wrong about that though, because the current Follistatin clinical trial has reported quite significant increases in the 6 minute walking distance month by month.  Follistatin is a drug injected directly into the muscle and it works only on that particular muscle.  At the moment, trials are being conducted on the quads which are the primary muscles used in walking.  If they wanted to test the drug on any other muscles, they would have to apply for separate approvals for clinical trials on each one, which of course could be quite a long process.

I stand by my opinion that the doses of BYM338 they are giving us are not really strong enough to overcome the effects of a progressive disease.  IBM left to its own devices progresses at about 5% per year.  The Phase 1 trial of BYM338 used a dose of 30mg per kilo of patient’s body weight, and achieved an improvement of 6% (average) on the 6 minute walk test.  The current phase of the trial is using doses of 10mg, 3mg or 1mg per kilo of patient’s body weight so can we really expect that to be enough to make us stronger?  Perhaps the best we can hope for at these doses is that it might slow down progression a bit.  That in itself would be useful.

The drug testing business is an unpredictable one though.  A few years ago we were all devastated when trials of another potential treatment for IBM, Arimoclomol, seemed to come to nothing.  Now researchers have decided that it is worth looking at again, and new larger trials are being prepared.  That drug works directly on the disease itself, altering the way muscle cells react to the destructive effects of IBM and stopping progression in its tracks.  So wouldn’t it be amazing if they could come up with a way to use all these therapies together?  Arimoclomol to stop the disease destroying our muscles.  BYM338 to repair the damage already done prior to diagnosis.  And Follistatin to ‘spot-repair’ the worst areas.

In the meantime, BYM338 trials are continuing.  We’re a little bit premature if we assume the drug has failed, or that it won’t be of use to us.  I personally hope that the investigators will have the common sense to look at the bigger picture, assess what other options we have available at this time (none!) and carry on with the work they have started, perhaps with either (a)  bigger doses, or (b) more realistic expectations.  I will of course update if I hear anything at all from the official sources.

This is just a hasty posting in case anyone is waiting to know whether I learnt anything new about the future of BYM338 yesterday.  I didn’t, sorry.  I will add this months progress stats in the next day or so, when I’ve had chance to get them together