AKV9 (NU-9) approved for clinical trial

Phase 1 study in humans

Prof. Ozdinler

Drum candidate AKV9 (formerly NU-9) has got the green light from the FDA for Phase 1 first-in-human study to evaluate safety and tolerability. Key member of the research team that developed the compound, Prof Hande Ozdinler, has foreshadowed potential applicability to the treatment of the HSPs, separate from its primary purpose at this stage, which is the treatment of motor neurone disease (ALS).

WINNETKA, Ill.–(BUSINESS WIRE)–Akava Therapeutics, Inc., a pioneering biopharmaceutical company focused on developing first-in-class small molecule therapeutics that act through inhibition of key pathways in neural crest-derived targets for a variety of neurodegenerative diseases and cancers, celebrates a significant achievement.

On July 3rd, the U.S. Food and Drug Administration cleared Akava’s Investigational New Drug (IND) application for the treatment of amyotrophic lateral sclerosis (ALS) to proceed with a Phase I first-in-human study in healthy subjects using Akava’s investigational new drug, AKV9 (formerly NU-9). The study will evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of AKV9.

SOURCE: Business Wire, August 22, 2023

Akava Therapeutics, Inc. Announces FDA Clearance of Investigational New Drug Application for the Treatment of Amyotrophic Lateral Sclerosis

Akava Therapeutics, Inc. press release


    1. Editor’s note: No, for 2 reasons – firstly it is a Phase 1 clinical trial. These are done with healthy people, with the aim of testing safety and tolerability of the drug candidate. If the trial progresses to Phase 2, participants with motor neuron disease (ALS) will receive the drug to determine its effect on the disease.
      Why this clinical trial is being closely watched by people with HSP is that this drug may work on a disease mechanism that some of the HSPs share in common with ALS and other neurodegenerative conditions as well. Success in this clinical trial for ALS would lead on to clinical trials for AKV9 to treat HSPs.

    1. Editor’s note: The best guess without knowing any of the design details is that the trial itself may take around 6 months, depending on a number of variables, any and all of which could alter this timeframe quite a bit. It is assumed that the trial will start with a group taking the lowest dose, with the results assessed before starting the next group on a higher dose, and so on. If they are well organised and have all the requirements in place to begin the trial, the results may be known by the end of March next year.

  1. If this ALS phase 1 clinical trial is successful and AKV9 drug is also suitable for treating HSPs, can ALS and HSPs be conducted in phase 2 clinical trials simultaneously?

    1. Editor’s note: A successful Phase 1 trial will most likely be applicable for the HSPs if the intended dosing range is similar. However separate Phase 2 trials would be necessary for ALS and the HSPs as these must be specific to a particular disease. An initial Phase 2 trial for the HSPs may focus on just one HSP type or possibly a group of HSP types with the same disease-causing mechanism. It is possible that several Phase 2 trials would need to be conducted to test treatment efficacy/effectiveness across a range of HSP types if there are initial signs of success to warrant this. These would be called Phase 2a trials for testing preliminary effectiveness. If successful, a number of multisite/multinational Phase 2b trials including larger numbers of participants would need to be conducted successfully as a minimum before gaining regulatory approval to market the drug. So it is a lengthy road – and a costly one.

  2. That’s very good news! I have HSP SPG7!
    Approximately how long could it take until there could be an effective medication! Thank you in advance for your response!

    1. Editor’s note: There is no way of estimating this. Until a therapeutic treatment is proven effective in a clinical trial, any time estimate is just a guess. Once effectiveness is established for a treatment, it could be available in a further 2-3 years once additional clinical trials have confirmed the results, regulatory approvals applied for and obtained, and the pharmaceutical industry produces and markets the treatment.

      1. Actually, ALS drugs can be approved much faster. Full approval can occur after a single successful phase 2, and can occur less than a year after the results are reported (see relyvrio). So approval is possible in 2025 or 2026 if it works.

  3. Will their be trials for those with HSP in the Houston area and when and where if you know? Thank you and thank you for all you have done for so many of us!!!

    1. Editor’s note: Way too early to know if there might be HSP trials in the future. They are starting with Phase 1 trials with the focus on ALS initially.

  4. Thank you for the update on the stages of research on AKV9 approval process. I am a Maryland resident with HSP Spg4 and will follow the results.

  5. Hi.
    My wife has hsp/spg4. She is 72 year old. The last years she feels sometimes more weakness in her legs so it is difficult for her to stand up from the wheelchair. Sometimes she feels weak, then she is not alert and then is difficult for her to do anything, Is it possible that hsp has this effect when she gets older, can it give her more general weakness?
    Thank for for the answer,

    1. Editor’s note: The two most prominent hallmarks of the HSPs in general are spasticity and weakness. The HSPs are also progressive diseases, meaning that they get worse with time – spasticity and weakness can both be expected to be more significant as time passes. Therefore, the weakness you describe in your wife’s legs, the difficulty standing, is consistent with this condition. Whether or not the more general weakness is related to HSP could only be assessed by her doctor or physiotherapist as there is a lot of variability from person-to-person regarding the amount and balance of weakness and spasticity. Some people with HSP are spasticity dominant with little weakness; others are weakness dominant with little spasticity – and everything in between. Regarding your wife not being alert sometimes when she feels weak, again, this is something that can only be assessed by her doctor. It may reflect subtle cognitive impairment that is common in the course of progression of the HSPs, or it may be age-related or it may be something else entirely, perhaps merely reflecting fatigue.

      1. I am 72 years old, my balance, weakness spasticity is getting a lot worse, can’t get up from chairs & have great difficulty with stairs
        Because of the way I walk & not using the muscles in my legs I have very swollen ankles & legs, taking fluid tablets is also a problem because of in continence, any suggestions of what exercise I could do to help with this problem.

        1. Editor’s note: Any advice will need to come from your own medical professionals taking into consideration the multiple issues at play, and with the knowledge gained from assessing your situation in person. A neurological physiotherapist or a physiotherapist with rehabilitation training, in conjunction with your GP and/or neurologist, would be a good place to start. They can then monitor outcomes and make adjustments to the treatment plan.

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