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Change to the design of Roche’s ongoing huntingtin lowering trial – known as the GENERATION HD1 study

The pharmaceutical giant Roche ran an earlier, smaller, study with antisense oligonucleotides or ASOs as potential HD treatments. That was a safety study – designed to determine whether or not giving ASOs via the spinal fluid led to any unexpected bad outcomes. The trial was a success – none of the participants had a bad reaction to the drug or stopped attending their monthly visits for injections and treatments.

At the end of that small safety study, Roche and Ionis made the decision to start giving all the participants, including those who had been receiving placebo treatments, the drug every month. Technically this is called an open-label extension study. Open-label just means that in this type of study, both participants and their physicians know what they’re receiving, which is different from the earlier double-blind study.

Assuming a drug is safe, and has a reasonable chance of working, being in an open-label extension study is a nice reward for the brave volunteers who signed up for the first trial of these drugs. It’s also good for the community and the drug company sponsoring the trial because they get a sort of sneak peek into the long-term effects of treating with the drug.

Roche have recently explained that they’d been treating people in the open label extension either

” We can’t predict the future, but we think you should stay tuned over the next year for more exciting updates on developments in huntingtin lowering treatments”.

monthly or every other month. The letter goes on to state: Review of nine-month data showed effects on lowering mutant huntingtin protein levels in the cerebral spinal fluid that support the exploration of less frequent dosing. Based on the totality of the data, including safety and tolerability, there appears to be no overall advantage to treatment monthly versus every two months.

It seems that Roche have seen results suggesting that lowering of the Huntingtin protein was good enough with 2 months between doses that they feel giving the drug every month might not be necessary. In fact, they’re making changes to the design of the GENERATION HD1 study to see if they can go even longer between treatments, by including a new group treated only every 4 months.

Needing to arrange injections of drug 3 times a year, compared to 12, would make a huge difference if this drug is approved for HD. But regulators are going to require that we demonstrate this is possible, so Roche are modifying the GENERATION HD1 study to include three treatment groups: a placebo group, a group treated every 2 months and another treated every 4 months.

A very important message here is that there’s no evidence that treatment with this drug has influenced
HD symptoms in any patients. All these decisions are based on lab tests suggesting the drug is having its desired effect in the brain (that is, lowering the amount of huntingtin protein), but we still don’t know whether this will be associated with an improvement in HD symptoms in treated patients. To do that, we have to run the full scale GENERATION HD1 trial.

These rapid advances in huntingtin lowering treatment are starting to come quickly. We can’t predict the future, but we think you should stay tuned over the next year for more exciting updates on developments in huntingtin lowering treatments.

In other research news, DutchAmerican company uniQure has received approval from the US drug regulator to begin the first ever gene therapy trial in Huntington’s disease. Their plan is to use a virus, injected into the brain, to turn cells into a factory that makes a weapon to lower the harmful huntingtin protein.

More on this next time, or here’s the link if you want to read the full HD-Buzz article https://en.hdbuzz.net/267

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