Phase 1 study in humans
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
Can we participate in this human study?
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.
Thank you for your answer. How long will the Phase 1 clinical trial take?
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.
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?
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.
Please let me know if they have AKV9 clinical trials in San Diego or LA. I live in San Diego but will drive to LA.
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!
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.
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.
I live in Rotterdam – Netherlands – Europe. Will this be available in Europe also? I’m on the verge of going downhill physically so it would be very welcome! I have HSP sgp4.
Editor’s note: if it is shown to be effective, hopefully it will be both available and affordable everywhere. Have a read through the other comments and replies. You will see that whilst approval to start a clinical trial in motor neurone disease has been granted, no trial has yet been initiated. So any news regarding this drug and HSP is still a long way off.
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!!!
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.
Editor’s note: Potentially yes. Variants in the ALS2 gene are associated with three overlapping conditions – see here for more: https://www.omim.org/entry/205100?search=als2%20gene&highlight=als2%20gene. Your neurologist and/or geneticist may be able to provide a more specific guide to potential applicability, but early days yet for this drug candidate, with a phase I trial planned.
My daughter has a mutation in the ALS2 gene. Would this be something that could potentially benefit her?
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.
My wife is an ALS patient and would like to participate in the trial
Editor’s note: The company developing this drug is Akava Therapeutics in the US. Contact them regarding your interest in the clinical trial. Their contact email is: https://akavatx.com/contact-us/
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.
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.
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.
Hi, are there any updates on the trial?
I have HSP sgp4. I live in Rotterdam in the Netherlands. Any news on this? In case of testing on humans i’d have no problem to fly to the US to participate.
Editor’s note: Unfortunately there is no news to report. The researchers received approval for a phase 1 clinical trial (safety and tolerability) some months ago, but a search of the clinical trials website clinicaltrials.gov returns no results for this candidate drug, which suggests that a phase 1 trial is yet to be initiated.
Where is the update on this? We never even got confirmation that the trial started. Also I’ve been writing you guys about my disability and some very scary complications that are potentially life threatening because I live in a pretty ableist community and no neurologists know or really care about my condition. And the worse thing is you don’t even post my comments because I had a mental breakdown in the comments section like 10 years ago. Please convince me this isn’t a scam site.
Editor’s note: Unfortunately there is no news to report. The researchers received approval for a phase 1 clinical trial (safety and tolerability) some months ago, but a search of the clinical trials website clinicaltrials.gov returns no results for this candidate drug, which suggests that a phase 1 trial is yet to be initiated.
Regarding you writing to us, our records show that you have posted comments on articles on seven occasions and they have been published. We do our best to respond to all comments, however there may be occasions where we have not replied to posts. We are an all-volunteer organisation and sometimes things just fall through the cracks.
This Facebook website about hsp https://www.facebook.com/Cure-SPG4-Foundation-102367475363776