On January 24, 2018, Robert Goldstein, Vice President and Chief Marketing Officer at the ALS Therapy Development Institute (ALS TDI), hosted a webinar on the top 10 things to watch for in ALS research in 2018.

  1. Radicava (edaravone)

Edaravone, marketed as Radicava in the US, is at the top of our list again as it is something which is making a difference in people’s lives today. It is the first drug to be approved for people living with ALS in more than two decades. As reported at the ALS/MND Symposium in Boston last December, there are currently 1,200 people accessing Radicava in the US with around 50% of these people receiving the drug in their home. There appears to be varying levels of success in accessing the drugs. According to conversations with clinical staff at the symposium, around 100 people prescribed the drug at Johns Hopkins Clinic while no one attending the clinic at Emory University. There are a number of factors preventing access to the drug including healthcare insurers not covering the drug under their plans and doctors reluctant to prescribe the drug to those who do not meet the original trial criteria. A full webinar on Radicava is available here.

  1. BHV-0223

New to our list of top ten things to watch for is a new formulation of Riluzole, a drug which was approved for treatment of ALS over 20 years ago. BHV-0223 is a sublingual drug meaning that it dissolves under the patient’s tongue making it easier for those with difficulty swallowing to take the drug. A recent study on the new formulation found that it had the same bioavailability as the pill form, meaning it is circulated around the body as effectively, and that it appears to have less toxicity in the liver. The company responsible for this new formulate, BioHaven Pharma, plans to file for marketing approval with the FDA in the first half of 2018.

  1. NP001

Third on the list is a drug from Neuraltus which has been studied for over five years in ALS. The company completed a phase 2 trial in 2012 and just finished a confirmatory trial in January, 2018. The company is planning to report on topline data from the most recent trial by the end of Q1 2018. Based on that data, it is expected that Neuraltus will decide to file for accelerated approval, or other paths, with the FDA or conduct additional trials.

  1. NurOwn

Often cited as the most exciting stem cell trial in ALS research, NurOwn is currently enrolling in 5 centers across the US for their pivotal phase 3 trial. This is the only phase 3 clinical trial enrolling people with ALS today. Each participant’s own, adult stem cells are taken from their spinal cord and induced to become specific support cells. Those support cells are design to secrete neurotrophins that support motor neurons when they are implanted back into the participant’s spinal cord over three infusion during the course of the trial. The design of this phase 3 study is being optimized by the company for “fast progressors,” as they were identified as a responder group through post hoc analysis conducted in earlier trials. In it important to note that participants cannot take edaravone while completing this year-long study.

If you’re interested in learning more about ALS stem cell studies, you can listen to our dedicated webinar here.

  1. AMX0035

Fifth on the list of things to watch in 2018 is a drug called AMX0035 from Amylyx Pharmaceuticals. AMX0035 is a proprietary combination of two compounds Tauroursodeoxycholic acid (TUDCA) and phenolbutyrate. Both compounds have been tested independently showing little efficacy when taken separately in slowing ALS. The company wants to test whether the drugs, when taken together, can reduce stress occurring within key components of a cell, namely mitochondrial stress and endoplasmic reticulum (ER) stress that seem to be related to ALS disease progression. This phase 2 trial is currently recruiting at 25 sites located throughout the US. One third of participants will be given placebo over the course of this 24 week trial. Participants are eligible if they are taking edaravone while enrolled and the company has suggested that they will offer a yearlong open-label extension arm of the study to those that complete the phase 2 trial should results be positive.

  1. Masitinib

AB Science’s Masitinib is currently the most advanced potential ALS drug in clinical trials right now. The treatment aims to target mast cells and macrophages, and prevent them from proliferating, which in turn may cause inflammation, among other issues that could influence disease progression rates. The original phase 3 trial of masitinib took place across eight locations in Europe with 100s of people enrolled. At the International Symposium on ALS/MND, the principal investigator, Jesus Mora Ph.D. said trial data showed a positive response at the higher dose of 4.5mg/kg of body weight, but that a confirmatory trial is warranted in his opinion. The company are currently waiting to hear from the European Medicines Agency (EU equivalent to the FDA) to see if they are authorized to market the drug in the EU. A phase 3 confirmatory trial of masitinib has already been listed on clincialtrials.gov, but the company has not provided information on enrollment sites or timelines.

  1. Gene Therapy

A topic gaining a lot of momentum at the moment in ALS and other neurological diseases is gene therapy. There are currently over 40 different genes associated with familial ALS. The two main targets for this type of treatment are for those individuals who test positive for mutations in the SOD1 gene and those who carry expanded repeats of the C9ofr72 gene. Biogen and Ionis Pharmaceuticals are currently working in collaboration on an SOD1 antisense oligonucleotides (ASO) phase 1 study which is currently enrolling people who are SOD1+. That trial continues to move forward with additional multi-dose cohorts being enrolled now. In response to C9orf72, there are currently three approaches.

  • In January, Pfizer announced that it was teaming up with Sangamo and entering the ALS research space using zinc finger proteins targeting C9orf72. The timeline for this approach is not yet known but it is unlikely that any clinical trials will begin before end of 2018.
  • Biogen and Ionis are planning a phase 1 antisense therapy trial on C9orf72 which is expected in 2018
  • And finally, Wave Life Sciences will start phase 1 ASO trial by end of 2018. We expect more information on each trial and their design later this year. (Since this webinar was held, Pfizer announced a major research collaboration with Wave Life Sciences including work on qn ALS project.
  1. Copper ATSM

Copper ATSM (CuATSM) is an exciting compound currently in a phase 1/2 clinical trial in Australia. CuATSM is unique in that it is the first drug to show efficacy in preclinical testing in three, independent labs - University of Melbourne, Oregon State Health University and here at ALS TDI. The ongoing trial in humans is divided into five cohorts each taking different doses from 3mg to 48mg per day. The study is too small and short to determine efficacy, but to date, there have been no adverse events reported according to a person involved in the study. There are rumors of a clinical trial in the US beginning by the end of 2018 but nothing has been posted online at this time. The trial will most likely target those who are SOD1+. Check out our clinical trials page for regular updates.

  1. AT-1501

AT-1501 is the most promising treatment tested at ALS TDI to date. Anelixis Therapeutics is currently working to get this potential therapy into a phase 1 clinical trial this year. The company has recently assembled a clinical advisory board of experienced names in ALS research such as Stanley Appel, M.D. (Methodist Neurological Institute) and Merit Cudkowicz, M.D. (Massachusetts General Hospital, Harvard Medical School). ALS TDI will continue to report on any updates from the company as it announces trial designs, timing, etc.

  1. Pimozide

Pimozide is an antipsychotic drug currently used to treat schizophrenia and Tourette Syndrome. A study completed in Canada in 2016 looked at a small cohort of 25 people living with ALS to test whether it could slow disease progression. No significant data showing efficacy was determined, but that was expected as the study was small and short. There was some concern around tolerability as four people dropped out with reports of restlessness particularly at doses of over 4mg. A follow up study is currently underway in Canada looking to enroll 100 people with 50% receiving 4mg of the drug and 50% taking the placebo. This study allows those who have been taking edaravone for at least two cycles and with disease onset within four years.

If you are taking any medications mentioned here, or any other treatments to combat ALS or you would just like to track your disease progression, the precision medicine program at the ALS Therapy Development Institute is an effective way to do this. Using accelerometers, voice tracking tools, and self-reported online ALSFRS-R, the PMP enables participants to track their disease progression, allowing them to see if their treatment plan is impacting their ALS progression - while also partnering with scientists at ALS TDI helping to advance our mission to end ALS.

If you have any questions on the content of this piece or on the work we do at the ALS Therapy Development Institute, please email us at letstalk@als.net.