. Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Feb;20(1-2):115-122. Epub 2019 Jan 22 PubMed.

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  1. The data shown here seems extraordinary in that the active group seemed to actually “improve” over the four-month trial period. If true, fantastic! But it reminds me a bit of the Italian trial of lithium—amazing results in a small cohort and completely negative results in a true placebo-controlled trial.

    Also, this is not a new target, and it is surprising that this company has come up with a magic bullet. Elysium Health is a bit of a controversial company, selling anti-aging pills, which I believe are at least related to EH301, over the internet. Maybe it’s all true, and I really hope it is, but I would like to see a larger multicenter trial done by another, independent group.

    View all comments by Jonathan D. Glass
  2. It is very remarkable and encouraging to see that the investigators report a clinical improvement in the ALS patients and not just a slowing of progression of this devastating disease. Findings like these urgently require independent confirmation.

    One has to keep in mind that this is a very small cohort at a single center, and such a trial design is very vulnerable to statistical outliers and other biases. Therefore an independent confirmation with a more robust study design that includes more patients, multiple centers, and ideally objective biomarkers such as neurofilaments and possibly a dose response is required before firm conclusions on the efficacy of this promising approach can be drawn.

    View all comments by Patrick Weydt
  3. I do think the data support proceeding to another study. I also encourage the company and investigators to develop biomarkers to measure the biological effects of treatment.

    It is, of course, exciting to see positive results in an ALS trial. The caveats—which are important—include that the study was very small, duration of follow-up short in the double-blind period, and that about one-third of people stopped treatment early. I couldn’t tell from paper how drop-outs were handled in the analysis.

    Because ALS is such a heterogenous disorder, results from small studies can sometimes not bear out when a larger confirmatory study is done (e.g., lithium and dexpramipexole studies). The data here is encouraging but not definitive. It would be important to move forward expeditiously, though, for a confirmatory trial in larger group of participants and for longer duration.

    View all comments by Merit Cudkowicz
  4. This was a randomized, placebo-controlled, double-blinded trial of EH301 (which elevates NAD+ and activates sirtuins) in patients with ALS. The authors concluded that that the drug was safe and associated with significant improvements, not just slowing of decline, in several important outcome measures including ALSFRS-R, MRC manual muscle testing, and forced vital capacity. Placebo-treated patients declined on all these measures at a rate consistent with that seen in other published trials. The authors call for a larger Phase 2 trial of EH301.

    There are several problems with interpreting the results of this study. First, the sample size was quite small (only 15 patients assigned to drug and 17 assigned to placebo). Following randomization, the two groups were unfortunately not well-balanced in disease duration and starting ALSFRS-R or starting MRC, meaning it is not clear how comparable they were even before they received any treatment. The duration of follow-up in the randomized trial was short (four months). In spite of this short duration, there were a surprising number of patients who did not complete the study in each group (5/15 in the drug-treated and 7/17 in the placebo-treated group).  We are told that none of the dropouts (or adverse events) were related to treatment, but no explanations were given for the “hepatitis” or “profound mental depression” that caused two drop-outs in the EH301 group. It does not appear that the data in this study were analyzed via “intention to treat.” By analyzing only those patients remaining in the study at each time point, biases may have been created. Finally, three of the authors of this study received salary support and stock options from Elysium Health, the company that owns EH301. This creates a potential for bias and conflict of interest.In spite of these problems I agree that these results warrant a follow-up trial. I hope that this new trial will have a larger sample size, longer duration, be clearer about the causes of adverse events, and utilize intention to treat analyses. It would also be nice if the follow-up study measured NAD+ or sirtuin activation and utilized different dosages of EH301 so we could see whether there is any dose-response curve on any of the clinical outcomes or biomarkers.

    One final question many patients will have is how EH301 compares to the over-the-counter supplement called Basis currently being sold by Elysium Health, which ALSUntangled reviewed in 2017. Hopefully Elysium Health will shed some light on this in the near future so patients can make an informed decision on whether they now want to try Basis for their ALS. 

    View all comments by Richard Bedlack
  5. This pilot study, although small, is very exciting. The fact that many of the patients taking the drug did not show decline in several clinical endpoints measured in the study is promising. The preclinical data available in cell culture models suggest that the two components of EH301 have the potential to engage multiple mechanisms that could be neuroprotective in the context of ALS pathology. Overall, this seems to be a promising, and reasonably safe, therapeutic approach for ALS treatment. Further confirmation in a bigger cohort will be necessary in order to establish its effectiveness to slow disease progression in patients with ALS.

    View all comments by Marcelo Vargas

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