HERCULES trial shows tolebrutinib slows progression in non-active secondary progressive MS

The HERCULES trial compared tolebrutinib with a placebo (dummy drug) in people with secondary progressive MS who are not experiencing relapses. The two GEMINI trials compared tolebrutinib with existing DMT teriflunamide (Aubagio) in relapsing MS. 

The company who make the drug (Sanofi) shared the results at the ECTRIMS conference today.  

They looked at whether the drug delayed ‘six month confirmed disability progression’. This is a worsening of disability on the EDSS that was still true six months later. 

Tolebrutinib delayed how long it took to see this disability worsening by:

• 31% compared to the placebo in non-relapsing secondary progressive MS
• 29% compared to teriflunamide in relapsing MS. There was no difference in relapses in relapsing MS.

What were the side effects of tolebrutinib?

There were some negative side effects of the drug. 

In particular, some people experienced injury to their livers during the first few months of treatment. For most people, this was resolved when they stopped taking the drug. But one person sadly died after needing a liver transplant.

Following this, the company added more frequent monitoring which reduced how severe the liver problems were.

When could tolebrutinib be available?  

After a positive phase 3 trial, any new disease modifying therapy (DMT) has to be licensed by the regulators. The regulators look at the data from the trial and decide whether the drug is safe and effective. Then NICE have to approve it to become available on the NHS. This process can take several years.  

The company said they’re going to use the results of the HERCULES and GEMINI trials for future conversations with global regulators.  

If it’s licensed and approved for use in the UK, tolebrutinib could become the first DMT for people with secondary progressive MS who don’t have relapses. Currently, there are two DMTs for secondary progressive MS, but you’re only eligible if you have active secondary progressive MS. That means you still have relapses or new lesions on MRI scans. 

What about primary progressive MS? 

A phase 3 trial in primary progressive MS, called PERSEUS, is still ongoing. We expect to see the results next year.   

How does tolebrutinib work? 

Tolebrutinib is a type of drug called a BTK inhibitor. This is a new type of drug for MS. Like all existing DMTs, it works by stopping rogue immune cells attacking the protective myelin coating around nerves. But it does this differently, which is why researchers think it’s effective at slowing progression.

Several other BTK inhibitors are being investigated for MS as well.  

• Read more about BTK inhibitors  

We still need to find ways to repair damaged myelin and protect nerves from damage too. So it’s really important we continue to support high-quality trials like our Octopus trial.  

A much-needed option 

Dr Emma Gray, our Assistant Director of Research says: 

This news is a huge win for the MS community. More than 150,000 people live with MS in the UK and many of those who have progressive forms of the condition have no treatment options to slow the worsening of their MS.

“We hope these results lead to positive discussions with the regulators. While this will take some time, if licensed and approved in the UK, we could finally have a treatment for people who have been waiting years. This research is further proof we’re edging ever closer to finding treatments for everyone living with MS.