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SCA Therapeutics Development

Last updated on November 3, 2024

This page lists some therapeutics (mostly drugs; sorted by company name) being developed for spinocerebellar ataxia (SCA)—leaning towards SCA3, which I have—and Huntington’s disease (HD). There are reasonably no claims to stop, prevent, or cure the diseases.

The National Ataxia Foundation’s take on this.

Why include Huntington’s disease?

The SCA that I have (SCA3) and HD both are polyglutamine diseases, and gene-based therapeutics for one can likely be stepping stones for the other. Though HD and SCA3 are genetically similar, the mutant toxic huntingtin protein affects the whole brain and especially the basal ganglia, whereas mutant toxic ataxin 3 primarily affects the cerebellum. In other words, the neurons that deteriorate and die are in the brain but different parts of the brain, so there could be different drug delivery mechanics. HD prevalence is higher than SCA prevalence and a worse disease, so it’s usually given higher priority. Polyglutamine-SCA therapeutics are quite literally waiting for success of some kind first with HD before attempts are made to ride on its coattails.

How different is Friedreich’s ataxia?

Friedreich’s ataxia (FA) and SCA(3) are different diseases. Will there be leverage between therapeutics, like I assume there will be for polyglutamine diseases such as HD and SCA(3)?

  • Since FA is autosomal recessive, the inheritance pattern is completely different from SCA. Also, FA comes on earlier and stronger and is fatal to children.
  • The prevalence of FA is about the same as all the SCAs combined. There are at least a dozen pharmaceutical companies working on therapies for FA but only a small handful working on SCA.
  • The genetic defect that causes SCA(3) is in an exon and causes a ubiquitous protein to become toxic primarily to the cerebellum. The genetic defect that causes FA is in an intron and causes a protein to not be created that is needed in various areas of the body, such as the brain and muscles (including the heart).
  • Because of the exon/intron situation, SCA(3) can be modified at the DNA or RNA level, but FA can be modified at the DNA level but not the RNA level.
  • Therapeutic approaches to each disease that don’t involve gene therapy tend to be entirely unrelated.
  • CRISPR with viral delivery might be able to repair billions of mature neurons with either kind of defect eventually. If this happens, then FA will probably be addressed before SCA(3) by a few years because of its higher prevalence and overall “worseness.”

Continuing…

See here for a general description of trial phases.

From this PDF, the overall probability of success was 63% in phase 1 trials, 31% in phase 2 trials, 58% in phase 3 trials and 85% during the regulatory review process, for an overall success rate (phase 1 to approval) of 9.6% (63% × 31% × 58% × 85% = 9.6%). The success rate of going from phase 2 to approval was 15% (three make it for seventeen that don’t).

The following lists are alphabetical.

Specific to SCA or SCA3

Biogen

  • www.biogen.com
  • Pipeline [find with Google]
  • Drug for SCA3
    • Code name: BIIB132 (those are ‘i’s; BIIB is the Nasdaq stock symbol for Biogen).
    • Added to pipeline in 2022 [find with Google].
    • Technology: ASO.
    • Administration: intrathecal.
    • NCT05160558 (phase 1)
      • 2022-02-02 through 2025-12-12 (about four years).
      • At UCSF.

Blade Therapeutics (maybe)

  • www.blademed.com; founded in 2015; in San Francisco, CA, U.S.A.
  • Pipeline [find with Google]
  • Drug for SCA3? This might be untrue, as they seem to still be finding their way (2021-10-24).
    • Code name: BLD-2736 [find with Google]
    • As of 2021-10-07, this is the only mention of SCA3 on the website.
    • 2021-10-24: this is where I first heard about this.

Lacerta Therapeutics (maybe)

  • lacertatx.com (on Twitter); founded in 2017; in Florida, U.S.A.
  • Approx. pipeline (interactive page only as of late-2020) [find with Google]
  • Founded in 2017 in Florida, U.S., there isn’t much to go on now in late-2020.
  • Viral (AAV-based) gene silencing for SCA3. No real details as of late-2020.
    • Term to know: capsid (protein shell of a virus).
  • Find with Google: Lacerta and ataxia

Vico Therapeutics

  • vicotx.com
  • Pipeline [find with Google]
  • Founded in Q4 2019 in The Netherlands, they have essentially no info on their website in early-2021.
  • Drug for SCA, possibly for polyglutamine SCA
    • Code name: VO659
    • Technology: ASO, slated to address HD, multiple SCAs, and Rett syndrome.
    • 2020-07-29. First news release, which reveals a tiny bit.
    • 2020-08-05. Technology licensed from OHSU (Oregon Health & Science University).
    • 2021-02-10. European Commission (EC) grants orphan-drug designation for VO659.
    • 2021-06-29. Orphan-drug designation (for SCA) in the U.S.
  • Find with Google: Vico and ataxia

Specific to SCA but a don’t-care

Biohaven, Ltd.

  • www.biohaven.com
  • Pipeline [find with Google]
  • Drug for SCA
    • Code name: BHV-4157 (link goes to my own assessment).
    • Generic name: troriluzole (renamed from trigriluzole; link goes to my own assessment).
    • Administration: by mouth.
    • Mechanism of action: reduces glutamate in the brain.
    • General goal: slow cerebellar degeneration by reducing needless excitement of neurons. No claims are made about stopping or preventing the disease.
    • Stage in 2017-November: phase 2 failed in the U.S. Yet it persists.
    • Skepticism alert.
      • The same drug is being tested with Alzheimer’s disease and OCD, indicating a hit-or-miss riluzole repurposing extravaganza.
      • A supposed-to-be-simple sublingual reformulation of riluzole failed to get FDA approval for ALS, and they dropped it like a hot potato.
    • 2022-05-23. SCA testing fails again.
    • 2022-05-26. And, again, “they” just can’t let it go.
    • 2023-07-27.  The end of troriluzole and SCA3.
  • 2022-05-10. Biohaven bought by Pfizer. My guess: this is only for their migraine medicine (Nurtec). I expect other drugs, such as troriluzole, to be eliminated completely. They deny this, of course, but mark my words: this spells the end for troriluzole.
  • Find with Google: Biohaven and ataxia

Cadent Therapeutics

  • www.cadenttx.com (acquired by Novartis on 2020-12-17)
  • Pipeline [find with Google]
  • Drug for essential tremor (ET) with possibly unspecified (or unknown) additional benefits for SCA.
    • Code name: CAD-1883. Note: with the Novartis acquisition in 2020, this seems to have fallen off the radar.
    • In early 2018, the website said that CAD-1883 was for those with SCA and ET, making it sound like you needed to have both SCA and ET to benefit. As of late 2018, they’ve decoupled the benefits to those with ET and those with SCA, but that only reveals the nebulous expectations on SCA: clearly, the drug is expected to help with ET (however acquired), but the expectations on SCA beyond ET (if any) have not been yet revealed. The prevalence of ET is so much higher than SCA, it really makes one wonder why they chose to highlight SCA at all. This is some odd chain-yanking.
    • Good term to know: SK channel (small conductance calcium-activated potassium channel).
    • Allosteric activator: improves regulation of brain activity to help restore motor and cognitive function.
    • No claims are made about this being an SCA disease modifier; rather, this is symptom relief.
    • 2018-03-12: transition to phase 1. Also announced a partnership with Saniona.
    • Possibly related to (in competition with) Cavion and their CX-8998 product.
      • CX-8998 in phase 2 trial from 2017-06 to 2018-09.
      • Let’s step back and let the pros spin failure.
    • 2018-11-15 (URL deleted 2021-01-23): ET testing is moving forward and SCA is falling behind (see the pipeline) for the same drug; in other words, the drug is for ET, and the mystery of why SCA is highlighted at all deepens.
    • 2019-05-29: FDA orphan drug designation, but the mystery deepens even further as to what the SCA benefits are supposed to be.
    • 2020-12-17. Cadent acquired by Novartis.
    • 2021-04-08 (?). “Withdrawn.”
  • Find with Google: Novartis and ataxia

Intrabio

  • intrabio.com
  • Pipeline [find with Google]
  • Kitchen sink drug for currently 19 maladies. A repurposing extravaganza?
    • Code name: the IB1000 series.
    • Generic name: acetyl-DL-leucine, sometimes given as acetylleucine or acetyl-leucine. It’s been sold since 1957 (60+ years now) under the brand name Tanganil (vertigo treatment).
      • Not to be confused with the amino acid supplement l-leucine, which is chemically different, though possibly similar.
      • The meaning of acetyl-.
    • Tanganil has been studied and taken for years, for SCA; I have no positive expectations.
    • 2018-12-05: “IntraBio Receives SCA European Orphan Drug Designation”
    • 2018-12-10: “IntraBio Receives SCA Orphan Drug Designation from the FDA”

Seelos Therapeutics

Steminent Biotherapeutics, Inc.

Vybion, Inc

Defunct (or presumed defunct)

Bioblast Pharma Ltd.

  • bioblastpharma.com (website gone on 2019-03-28)
  • Therapeutic for SCA3
    • Code name: Cabaletta.
    • Generic name: trehalose, a disaccharide in the same family as table sugar (sucrose).
    • Administration: intravenous.
    • Described by Bioblast as a mutant protein stabilizer.
    • Described here as an autophagy enhancer.
    • General goal: slow cerebellar degeneration. No claims are made about stopping or preventing the disease.
    • 2016-November: phase 2a successful and complete in Israel (see next section). NCT02147886.
  • Find with Google: Bioblast and ataxia

News:

  • 2017-01-18. Bioblast published positive phase 2a trial results. SCA3 progression did not worsen in 14 people after 6 months nor in 5 people after 12 months.
  • Bioblast has spent most of 2017 in financial trouble, seeking partnership or merger opportunities. The company is using JSB Partners to assist in business development.
  • 2018-01-04: Trehalose has been dominating the news with how it might be proliferating some fatal superbugs.
  • 2018-11-19. Merger with Enlivex. Bioblast will go away. Bioblast will try to sell off Cabaletta.
  • 2019-02-19. Cabaletta sold to Seelos Therapeutics. It’s called SLS-005. See above.
  • 2019-03-22. Therapeutic trehalose lives! Including for SCA3.

Dystrogen

  • dystrogen.com
  • Pipeline [find with Google]
  • Drugs tailored for polyQ diseases like HD and SCA3
    • Code name (for SCA3 therapeutic): DYST202
      • Pre-pre-clinical in 2019.
    • Technology: based on RNAi, and it’s viral!
      • Patent applied for in 2014; received in 2018.
    • Administration: intrathecal.
    • 2019-01-xx: a highly-informative PDF, likely to be removed soon.
    • 2019-04-05: honesty abounds as they have not reached the nonsensical marketing stage yet. The hope is to significantly delay symptoms.
    • 2019-November: discontinued.
  • Find with Google:

Ionis Pharmaceuticals, Inc.

Triplet Therapeutics, Inc.

  • www.triplettx.com; founded in 2019-12; in Massachusetts, U.S.A.
    • 2022-11-07: domain registration waned; company defunct.
  • Drug for SCA3
    • Code name: TTX-3360
    • Approach: DDR (DNA-damage response)

uniQure nv

  • www.uniqure.com; founded in 1998; in The Netherlands and Massachusetts, U.S.A.
  • Pipeline [find with Google]
  • Drug for SCA3
    • Code name: AMT-150 (following in the footsteps of AMT-130 for HD).
    • Technology: AAV5-based gene silencing
      • AAV5 = adeno-associated virus, serotype 5
        • AAV is the delivery mechanism, not the gene-silencing mechanism.
      • Gene-silencing technology (miQURE™) is a form of RNAi similar to miRNA (in the same family as ASOs).
      • miQURE™ lodges inside neurons and though it does not modify the genome (DNA) like CRISPR would, it permanently modifies the neurons so that any future protein they create is repaired / silenced (via RNA) by the viral payload that stays there.
    • “AMT-150 is a one-time, intrathecally administered, AAV gene therapy incorporating the company’s proprietary miQURE™ silencing technology that is designed to halt SCA3 in early manifest SCA3 patients.”
      • Note: AMT-150 (for SCA3) is administered intrathecally, whereas AMT-130 (for HD) is administered intracranially (i.e., into brain tissue via holes drilled into the skull).
    • 2019-05-07. Progress with AMT-150.
      • AMT-150 in mice.
    • 2020-10-27. Progress with AMT-150.
    • 2022-02-25. “Deprioritized” and removed from pipeline.
  • Find with Google:
  • In 2018, uniQure’s claim to fame was having the most expensive pharmaceutical ever produced (also viral and long-acting). Only 31 people in the world took it, and it was discontinued.
  • News for AMT-130 for HD
    • 2019-01-22. FDA clearance.
      • FDA clearance enables initiating its planned dose-escalating, randomized, and controlled phase 1/2 clinical trial to assess safety, tolerability, and efficacy.
    • 2019-01-29. A detailed article.
    • 2019-02-18.  Some success with ALS and miQURE™ (in mice).
    • 2019-04-08. FDA fast track status granted.
    • 2019-07-17. News + details.
    • 2020-06-19. Clinical progress.
    • NCT04120493: 2019-09-06 through 2026-05.
    • 2021-04-15. Progress.
    • 2022-02-07. Open-label Phase 1b/2 clinical trial begins.
      • 2022-03-21. Completion of enrollment in the first two cohorts.
  • 2021-03-29. Did gene therapy for hemophilia cause liver cancer? Independent investigation concludes No, but people are spooked.
  • 2022-08-29. Side effects.

Roche

Shionogi & Co., Inc.

Wave Life Sciences

Huntington’s disease, preclinical

Sangamo Therapeutics, Inc.

Spark Therapeutics

Others

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Jens-Ingo Farley

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Comments

8 responses to “SCA Therapeutics Development”

  1. Sheng Lu Avatar
    Sheng Lu

    complete and all-around !!!

    Reply
  2. zeming Avatar
    zeming

    Hello, I contacted collegue of Dr. Hayley from Michigan U who is working on ASO therapy to treat SCA3. They just post a clinical trials to look for 100 patients in US to find the right biomarker. If you can help them to find enough patients which they are short of, please contact
    kaisert . The clinical trials is on https://clinicaltrials.gov/ct2/show/NCT03885167

    Reply
  3. Stephanie J Blake Avatar
    Stephanie J Blake

    Thank you for these, I’m SCA1 (known for 17 years since tested after dad was diagnosed), these links are extremely helpful – Ive been involved with research at Univ of Minn for 10 years, and always on the look out for pharma companies and pipelines, I think if one thing is done for a specific polyglutamine SCA it will be beneficial for all the rest. I take mitoq10 supplement and feel likes its helping a bit. Just started mild symptoms this year.

    Reply
  4. Zeming Avatar
    Zeming

    Hi, I am a SCA3 patient who has earnt more than 20 million USD. Is there any way to accellarate the gene therapy such as ASO or AAV? e.g. donation or build a fund? and is there anyway to promise me to get the gene therapy ASAP? e.g. extended access or some other ways?

    Reply
    1. Jens-Ingo Farley Avatar
      Jens-Ingo Farley

      I have no authority to answer your questions, though I seriously doubt you’d be able to accelerate development, and I think obviously you’d not be able to buy a position in line. The idea of buying a promise is unfounded as no one can promise FDA approval of a trial before the trial.

      Reply
  5. zeming Avatar
    zeming

    Hello, how are you doing right now? I invested in a company that produce the ASO drug to treat SCA3. That drug may be on human in 2 months. What a bright future.

    Reply
    1. Jens-Ingo Farley Avatar
      Jens-Ingo Farley

      What’s the status now?

      Reply
      1. zeming Avatar
        zeming

        I have been injected. Improvement is obvious, but the continuity is not sure.

        Reply

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