What does the drug do?

WVE-004 is an investigational gene therapy being developed by Wave Life Sciences, and is specifically designed for MND caused by a mutation in the C9orf72 gene. WVE-004 uses an approach known as ‘antisense’, where the drug directly interferes with the faulty instructions for making a protein.

The C9orf72 gene contains three different sets of instructions (RNA) to make the C9orf72 protein and these three RNA are called V1, V2 and V3. In some forms of MND, mutations in the C9orf72 gene cause the V1 and V3 instructions to be faulty and this leads to the production of toxic proteins which build up in the neurons. WVE-004 targets the faulty V1 and V3 RNA and signal to the cell that they need to be destroyed, leaving the V2 instructions functional so that healthy version of the C9orf72 protein can still be made.

Trial Outcome

WVE-004 was found to be safe and well-tolerated and levels of a key biomarker, known as poly(GP) was reduced for those taking WVE-004. This lowering of Poly(GP) indicated that WVE-004 lowered levels of toxic proteins which are thought to play a role in C9orf72 MND/FTD. Unfortunately, WVE-004 was not shown to have any clinical benefit for people living with MND or FTD. No significant difference was observed by ALSFRS-R between those who took WVE-004 and those who took the placebo. Wave Life Sciences has now decided to discontinue the development of WVE-004.



Clinical Trials

Phase 1b/2a - FOCUS-C9

The Phase 1/2a study aimed to assess the safety and tolerability of different doses of WVE-004 in those with MND. The multi-centre study took place at several sites across nine different countries, including the UK. This trial aimed to recruit 42 participants and  participants were randomly assigned to receive either the placebo or one of four different doses of WVE-004 for a total of 24 weeks. You can find out more about the trial here.

Latest News


May 2023- Top line results were announced that WVE-004 did not show clinical benefit when compared to the placebo.


April 2022  - Interim results show some reduction in key biomarker Poly(GP). Further results expected in 2022. You can find out more here


July 2021 - The WVE-004 trial opened for recruitment

Last updated: 15/02/2022