Experimental immunotherapy shows promising trial results

• Unlike most available MS medications which suppress or modify the immune system, immunotherapies aim to ‘re-educate’ the cells of the immune system to prevent them responding to a specific target
• Experimental immunotherapy ATX-MS-1467 aims to retrain the immune system’s response to myelin, and previously showed good results in laboratory models of MS
• A Phase 1b clinical trial tested the safety of ATX-MS-1467 and found it to be well tolerated
• A Phase 2a clinical trial showed that the treatment was able to reduce lesions on magnetic resonance imaging (MRI)

Encouraging results from two early-stage clinical trials of ATX-MS-1467, an experimental new immunotherapy for people with MS, suggest that ‘re-educating’ the immune system may prevent attacks on myelin.

Previous research into ATX-MS-1467 showed good results in a laboratory model of MS. In these two new studies, researchers conducted clinical trials in a small number of people with relapsing MS to test for safety (Phase 1b trial) and effectiveness (Phase 2a trial). The results have now been published in the journal Neurology.

MS occurs when the immune system mistakenly attacks and destroys myelin, the protective layer that insulates nerves in the brain and spinal cord. Most current treatments for MS act by suppressing or ‘resetting’ the immune system to stop these attacks on myelin. However, immunotherapy takes a completely different approach, ‘re-educating’ the immune system cells responsible for MS attacks in order to reduce the chances of a relapse.

Myelin is made up of a range of fat molecules and some proteins. In MS, the immune cells mistakenly target some of the protein components of the myelin, including parts of one protein known as myelin basic protein.

ATX-MS-1467 is made up of a cocktail of four different protein fragments from myelin basic protein. The protein fragments are injected under the skin and are able to ‘teach’ immune cells not to attack myelin basic protein. This essentially retrains the immune system to recognise myelin as ‘self’, with the aim of preventing the myelin damage seen in MS.

Phase 1b clinical trial

The Phase 1b clinical trial compared two routes of administration of the drug: intradermal injections (injections into the skin just below the outermost layer) and subcutaneous injections (deeper injections into the fat layer below the skin). A range of doses were compared in 43 people with relapsing MS. Participants received an injection every two weeks for 16 weeks and were then monitored for a further 32 weeks. This study showed that, while there were some mild and moderate side effects, ATX-MS-1467 was well tolerated and the intradermal injections emerged as a better method for delivering the immunotherapy.

Exploratory investigations into the effectiveness of the treatment in the Phase 1 study indicated that it may have some temporary effect in reducing the gadolinium enhancing lesions on magnetic resonance imaging (MRI), a marker of active disease. However, lesions did return to pre-treatment levels during the 32-week period without the medication.

Phase 2b clinical trial

The Phase 2b clinical trial was designed to more thoroughly examine the effectiveness of the treatment in 37 participants, compared with baseline levels of the disease. Participants were given treatment for 16 weeks then monitored for a further 16 weeks with no treatment. As in the first trial, the Phase 2b trial showed that ATX-MS-1467 was able to reduce gadolinium enhancing lesions on MRI at the end of the treatment period, but also showed that this reduction persisted over the shorter 16-week follow-up period. The Phase 2b trial also showed that ATX-MS-1467 reduced the number of new or enlarging lesions on MRI.

Participants did not have significant reductions in their expanded disability status scale (EDSS) or MS functional composite (MSFC) measurements, both of which assess levels of disability in the clinic as a result of the treatment. However, the short duration of the trial would make it difficult to reliably detect any changes in disability.

These promising results imply that retraining the immune system to prevent attacks on myelin may be an effective strategy and that further clinical trial testing of ATX-MS-1467 in larger groups of people with MS is warranted.

With thanks to MS Research Australia – the lead provider of research summaries on our website.