A cautious welcome for the latest results from IONIS Phase One Trial

So, after posting an article this morning about the inevitable lull since IONIS released the results of its phase one trial, they have now issued a press release providing additional results from their analysis of the phase one study.

You can see it by following this link http://ir.ionispharma.com/news-releases/news-release-details/new-data-ionis-htt-rx-phase-12-study-demonstrates-correlation

Let’s do a quick recap on what IONIS said in January. They said that the experimental drug (now called Roche 6042) showed:

49% mean reduction in the faulty protein (40%-60%), but levels still declining at six months after start of treatment. IONIS believe, based on the work they did prior to this trial in animal models that this will result in a 55%-85% reduction in the cortex of the brain (largest part of the brain).
Participants were all on different dosing regimes and once they have identified the best dose levels, it is likely to increase the drug impact. (90mg – 120mg dose seems to be point beyond which there is no additional benefit).
All dose level demonstrated reduction in the faulty protein with a direct correlation between dose and reduction of the faulty protein. (dose levels were, 10, 30, 60, 90 and 120mg). Reduction appeared on average three months after treatment began.
Distribution of the drug in the brain is very good and compares with same treatment in Spinal Muscular Atrophy. Greatest effect is in cortical neurones, but perfuses all areas of the brain. Less reduction in the caudate nucleus which is the mid brain structure most susceptible to the toxicity caused by the faulty protein, but still significant improvements (35-50%)
IONIS talked about the fact the drug which targets just the faulty copy of the gene might need five different versions in order to treat everyone with HD whereas IONIS Httrx (they need a better name!) can treat everyone with HD with one drug.
Since the drug affects both the faulty and normal copy of the gene, they looked at the effect of lowering the normal copy of the protein, but in adults there appears to be none.
The safety profile of the drug is very good. There were no adverse events in any of the participants who received the drug. One person who received placebo, was hospitalised briefly, for monitoring following headache.
46 patients – mainly early stage HD
Participants received monthly doses, by intra-thecal (spinal) injections

Yesterday, IONIS released what they are calling exploratory clinical results; they have been looking to see whether the reduction in levels of the protein that causes HD translated into improvements in symptoms.

Their data suggests that individuals in the phase one trial did show meaningful improvements in their symptoms at three months after the commencement in treatment, but there are lots of caveats.

Remember, only 46 people were in the phase one trial; that’s too small a number to draw any conclusions about how the drug will work in the wider population of people living with HD.
The trial itself was not designed to investigate the impact of the drug on symptoms; the clinical data they analysed was reviewed after the phase one trial ended.
The data does not show that compared to people on the placebo, there was an improvement in symptoms; that comparison has not been done.
No one yet knows whether the reduction in the levels of Huntingtin will be maintained or what impact this will have, if any, on symptoms, over a long period of time.

I think the new information from IONIS is encouraging, but we really have to wait until the phase three trial which will be designed to investigate whether lowering the levels of Huntingtin really does have an impact on symptoms. In the meantime, the HD community can permit itself at least a smile at these encouraging, early results.