Symposium Blogathon: Focus on… Clinical Trial Updates (part 2)

Symposium Blogathon: Focus on… Clinical Trial Updates (part 2)

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This blog is part of our Symposium Blogathon series – where we are counting down to the 33rd International Symposium. Numbers in bold blue type correspond to the code in the abstract book. Click on the number to be redirected to the full abstract.

Clinical trials are research studies in human volunteers that determine whether potential treatments are safe and effective. Clinical trials are usually conducted in four progressive phases which check for safety and efficacy, establish the correct dosage and method of delivery, and assess the drug’s ability to treat the condition it is designed for.

A number of ALS/MND clinical trials this year are reflected at the International Symposium on ALS/MND, with presentations on a wide variety of different potential treatments.

In the second of our two-part clinical trial update blogs, we take a closer look at the talks and posters from this year’s Symposium which will be providing updates on current clinical trials for potential new ALS/MND treatments. You can read more about the clinical trials which will be discussed in part 1 here.


AMX0035 is a combination therapy which was recently approved for the treatment of ALS/MND in the United States and Canada. AMX0035 is a combination of sodium phenylbutyrate (PB) and taurusodiol (TURSO or TUDCA). The two compounds are though to target the disease in slightly different ways, with PB reducing stress on the endoplasmic reticulum, whilst TUDCA blocks key cell death pathways. This dual approach is believed to improve the survival time of neurones.

AMX0035 has been tested in a Phase 2 clinical trial called CENTAUR. This trial found that AMX0035 had a relatively small slowing of disease symptoms and had 6.5-month difference in survival who those who received AMX0035 compared to those who received placebo. Amylyx, are conducting a Phase 3 trial called PHOENIX. In poster CLT-24, Amylyx will provide an update on the PHOENIX trial, including participant enrolment and progress.

AMX0035 is also discussed in poster CLT01, highlighting the results of an independent expert review of some of the adverse events noted during the CENTAUR trial.

Poster CLT-07 also discusses AMX0035 by giving updates and learnings from the expanded access programme. Expanded access programmes allow access to investigational therapies for people who were not eligible for the clinical trial.

PHOENIX is still recruiting in the UK; you can find out more about this trial on our website.

Blog | 30 September 2022 | Charlotte Roy
What does the FDA approval of AMX0035 mean for the UK MND community?

WVE-004 (FOCUS-C9)

WVE-004 is a potential treatment that has been specifically designed against the part (an extra bit of DNA that is repeated many times) of the genetic code of the C9orf72 gene that is the most common genetic cause of ALS/MND and frontotemporal dementia (FTD). The treatment is an antisense oligonucleotide (ASO) which means it specifically targets and interferes with the faulty genetic instructions to prevent the repeat from making a toxic protein and restoring the correct amount of  the healthy C9orf72 protein to be made.

The FOCUS-C9 trial is a phase 1/2 clinical trial which aims to assess the safety, tolerability and also how the drug behaves within the body (pharmacokinectics and pharmacodynamic effects). Wave Life Sciences have announced interim results from the trial throughout 2022. These results have showed a reduction in a potential biomarker known as Poly(GP) with low single doses of WVE-004, which indicated target engagement of the drug. These results and additional new data emerging from the trial will be presented in poster CLT04.  

FOCUS-C9 is still recruiting in the UK, you can find out more about this trial on our website.

Tegoprubart (AT-1501)

Tegoprubart is an antibody against a protein called CD40 ligand (CD40L). CD40L plays a role in regulating the immune response, which can trigger inflammation of the spinal cord. The CD40L pathway has been found to be overactive in people living with ALS/MND. It is hoped using Tegoprubart to inhibit CD40L could block or delay the activation of the damaging inflammatory immune response.

Tegoprubart is being tested in a Phase 2a clinical trial to investigate its safety and tolerability at 4 different doses. Trialling different doses in a clinical trial is a key step of a testing a new potential treatment, helping to determine the correct dosage. The trial found Tegoprubart to be safe and well tolerated. The poster CLT02 will further discuss the results from the trial and highlight how the functional effect of Tegoprubart is dose-dependent.

Blog | 13 April 2022 | Charlotte Roy
12 MND Clinical trial updates to keep an eye out for in 2022 – Part 1

News in brief

Many other clinical trials are also being discussed including:

CLT08 – reports on the phase 1 clinical trial evaluating the safety and tolerability of an investigational drug called QRL-201 in people living with ALS/MND. QRL-201 is an antisense oligonucleotide aimed at restoring the Stathmin-2 gene, which is the most consistently decreased gene in ALS/MND across multiple studies.

CLT09 – discusses the results of the phase 1 clinical trial of DNL343. DNL343 has been shown reduce some of the effects of the stress response and have neuroprotective effects in pre-clinical (laboratory) studies.

CLT10 – gives an update on the phase 2 clinical trial of EPI-589 (EPIC-ALS). EP1-589 is thought to help reduce oxidative stress which is known to have an impact in ALS/MND.

CLT12 – reports on the safety and tolerability results of the phase 1/2a trial of IPL344. IPL344 has been shown to reduce inflammation and cell death, as well as behaving in a protective manner in pre-clinical studies.  

CLT15 – provides an update on the phase 2b trial of PrimeC (PARADIGM) in people living with ALS/MND. PrimeC is thought to influence three key pathways that are known in the disease, including neuroinflammation, accumulation of iron and the disruption of microRNAs which are vital in the function of motor neurones.  

CLT19/CLT22 – both discuss phase 3 clinical trials investigating oral edaravone (MT-1186-A01/MT-1186-A02). These posters discuss the safety and tolerability of oral edaravone, as well as investigating different doses of the drug. Edaravone acts as ‘free-radical scavenger’ by mopping up free radicals that are a result of oxidative stress.

CLT29 – reports on the phase 2 clinical trial investigating the effect of Salbutamol on walking capacity in people living with ALS/MND. Salbutamol is thought to act on a range of pathways which are impacted by the disease, including inhibiting the breakdown of protein, stimulating the production of proteins and growth factors that important for the development and survival of neurones.  

Stay informed

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Take a look at the schedule of blogs for November as we continue counting down to the 33rd International Symposium on ALS/MND with our Symposium Blogathon.

To listen to talks live, take part in the Q&As and visit the live poster sessions, register for the International Symposium now.

I work in the Research Development team as a Senior Research Information Co-ordinator. I graduated from the University of Nottingham with a PhD in Chemistry in 2020. After finishing my PhD, I joined an R&D company based in Nottingham where I spent my time synthesising potential new drug treatments for a wide variety of diseases. As part of my role I will help the team communicate the latest MND research on this blog, as well as on our twitter page (@MNDResearch).