In case you missed the webcast from IONIS, here are the main points:
- 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
Next steps
- Open label study following completion of the phase one trial is allowing for further analysis of the efficacy of the drug
- Next trial will be a randomised double blind study (some people will get the drug and some placebo)
- Next trial likely to last at least two years, but possibly longer depending on the data they are able to collect.