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Mnd Nz Research Network

Wave Life Sciences: FOCUS-C9 trial

Wave Life Sciences Ltd is a genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases.  They have developed an investigation drug WVE-004, and it is specifically designed for MND caused by a mutation in the C9orf72 gene or C9orf72-associated frontotemporal dementia (FTD).

What does the drug do?

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 RNA instructions. RNA (ribonucleic acid) is an acid in the chromosomes of the cells of living things which plays an important part in passing information about protein structure between different cells.

In some forms of MND, mutations in the C9orf72 gene cause two of the RNA to be faulty and this leads to the production of abnormal proteins that form toxic clumps inside cells.

WVE-004 is designed to reduce these toxic proteins’ production by interfering with the faulty sets of RNA and signal to the cell that they need to be destroyed. The remaining set of RNA is functional and goes on to produce a healthy version of the C9orf72 protein.

Phase 1b/2a - FOCUS-C9

The Phase 1b/2a study known as FOCUS-C9 aims to evaluate the safety and tolerability of WVE-004 in people with MND or FTD with a documented mutation in the C9orf72 gene. This study started recruitment last year and is continuing to recruit across Europe, Canada, Australia and now New Zealand. In this study, participants with FTD or MND are being given a single dose of WVE-004 or a placebo administered via injection through the spine (intrathecal injection).

In April 2022 the company released preliminary data reporting that the drug had shown a marked decrease in poly(GP) levels in the cerebrospinal fluid (CSF), the liquid around the brain and spinal cord, in comparison to the placebo group. Poly(GP) is one of the toxic proteins produced from the faulty RNA in the C9orf72 gene.

“ALS and FTD are serious, life threatening disorders where advances in disease-modifying therapeutics have been extremely limited. While early, these data are encouraging and open an opportunity to target the disease at the RNA level,” Merit Cudkowicz, MD, chair of the FOCUS-C9 clinical advisory committee, said in a press release. Further enrolment of participants will provide more data to help better understand the effect of this study drug.

The principal investigators for New Zealand, are Professor Tim Anderson in Christchurch and Dr Julian Bauer in Auckland and they recruiting participants from anywhere in NZ to this study.

Am I eligible to participate?

If you have been diagnosed with C9orf72 associated MND or FTD you may be eligible. Similarly if you have a known C9orf72 gene mutation and are beginning to show signs of MND/FTD but have not been formally diagnosed you may be eligible to participate.  There are several inclusion and exclusion criteria for the trial. Click here to read the inclusion criteria.  If you’d like to learn more please contact us and we can discuss it further.

How can I find out more information

Below are some links providing more information about the trial.

If you’d like to learn more please contact us and we can discuss it further.

Addition resources

ALS News today –‘WVE-004 Reduces Toxic Proteins, Early FOCUS-C9 Data Suggests’. Click here to read this article.

Wave Life Sciences April 2022 - Interim results show some reduction in key biomarker Poly(GP). Further results expected in 2022. Find out more here.

MND Research Blog – “Clinical trials to keep an eye out for in 2022”. Scroll down to read theWVE-004 (FOCUS-C9). Find out more here. – This is a registry of all clinical trials. “Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD) (FOCUS-C9)”. Click here to read more information about this clinical trial.

Wave life science; FOCUS-C9 trial - Inclusion Criteria

MND-Specific Inclusion Criteria:

  1. Diagnosis of MND based on clinical manifestations.
  2. Patients receiving riluzole have been on a stable dose for a minimum of 30 days.
  3. Patients on edaravone have received a minimum of 1 cycle (28 days).
  4. Patients discontinuing riluzole or edaravone had the last dose administered ≥1 month prior to Screening.

FTD-Specific Inclusion Criteria:

  1. FTD: Must have Global Clinical Dementia Rating plus NACC FTLD score of 0.5 or 1.
  2. FTD: Able to undergo periodic magnetic resonance imaging (MRI) of the brain. Patients

with mixed phenotype (MND and /FTD) need not undergo MRI if their MND symptoms prevent it.

Mixed Phenotype (MND and FTD) Inclusion Criteria:

  • Patients who are mixed phenotype (MND and FTD) must meet both the MND-specific and FTD-specific criteria.

Inclusion Criteria Common to Both Diseases:

  1. Patient must have the ability and be willing to provide written informed consent prior to any trial-related procedures.
  2. Documented mutation (GGGGCC [G4C2] repeat expansion) in the first intronic region of the C9orf72 gene.
  3. Body mass index (BMI) ≤32 kg/m2.
  4. Forced vital capacity (FVC) of >50% predicted.
  5. Age of ≥18 and ≤80 years at Screening visit.
  6. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, trial restrictions, and all trial procedures.
  7. Willingness to practice highly effective contraception for the duration of the trial if patients or their partners are of childbearing potential.