Approved and past drugs

Lighthouse II was an academic trial, not a company project. Macquarie University in Sydney was the official sponsor, working with King's College London and the European TRICALS network. It ran at 29 centres in Europe, the UK, Australia and New Zealand.

Company website ↗

Our DNA carries genes left behind by ancient viral infections. The researchers think some of these (HERVs) are switched back on in people with ALS and can kill nerve cells. Triumeq combines three HIV drugs (dolutegravir, abacavir and lamivudine) that block retroviruses, so the idea was that it might stop this HERV activity.

Scientific name: Human endogenous retrovirus K (HERV-K)

On 5 April 2025 TRICALS, King's College London and Macquarie University announced the trial was terminated because the interim analysis showed no benefit on survival. Patient organisations in the UK and Australia concluded Triumeq is not believed to help people with ALS/MND. Full results are still to be published.

Not shown to work. Controlled trials found no benefit.

The main goal was to see whether Triumeq helped people live longer. A planned interim look at the data showed no difference in survival between Triumeq and placebo, so the trial was stopped. The earlier Phase 2 Lighthouse study had hinted at slower decline, but it was small and had no placebo group, which is why a large placebo-controlled trial was needed.

All key studies

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  Lighthouse II (Phase 3)No benefit

  2025 · Placebo-controlled · Phase 3 · 419 people · Independent

  Stopped early in April 2025 after a planned interim analysis showed no survival benefit, the main goal, compared with placebo. Detailed numbers have not been published yet.

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  Lighthouse (Phase 2a)Mixed

  2019 · Open-label · Phase 2 · 40 people · Company and academic

  The main goal was safety, and Triumeq was well tolerated over 24 weeks. Decline on the ALSFRS-R seemed about 22% slower than before treatment, but the range included no effect and there was no placebo group.

Results from different trials can't be compared directly. How to read effects

The trial enrolled adults with ALS and excluded people who carry the HLA-B*5701 gene variant, because they can have serious allergic reactions to abacavir, one of Triumeq's ingredients.

How it's taken: Pill, once daily

Denali Therapeutics is a US biotech company developing medicines for neurodegenerative diseases. It provided DNL343 to the HEALEY ALS Platform Trial as Regimen G and later wound down the programme.

Company website ↗

When cells are stressed, they switch on the integrated stress response, which slows protein production and can lead to clumps called stress granules. In ALS these are linked to TDP-43, a protein that clumps in motor neurons. DNL343 activates eIF2B, a protein that helps turn this stress response off, in the hope of protecting neurons.

Scientific name: eIF2B activator (integrated stress response inhibitor)

The January 2025 topline results showed no benefit, and a follow-up analysis showed no effect on nerve-damage markers. Denali stopped the extension and HEALEY investigators concluded further ALS study was not warranted.

Not shown to work. Controlled trials found no benefit.

In the trial, 186 people received DNL343 and 139 received placebo for 24 weeks. The published results showed a disease rate ratio of 1.04, where 1.0 means no difference, so decline was about the same as placebo. It also did not lower neurofilament light.

All key studies

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  HEALEY ALS Platform Trial, Regimen GNo benefit

  2025 · Placebo-controlled · Phase 2/3 · 325 people · Company and academic

  Missed its main goal: decline in function and survival over 24 weeks was about the same as on placebo. Muscle strength, breathing and the nerve-damage marker NfL did not differ either.

Results from different trials can't be compared directly. How to read effects

The HEALEY trial enrolled adults with ALS at sites across the USA. People in this arm took 200 mg of DNL343 by mouth each day, or placebo.

How it's taken: Oral, once daily

Calico is a research company funded by Alphabet (Google's parent). It developed fosigotifator together with AbbVie, but AbbVie ended its partnership with Calico in November 2025. Calico continues to develop the drug for vanishing white matter disease, not ALS.

Company website ↗

When cells are under stress they press a "brake" on making new proteins, called the integrated stress response. In ALS this brake may stay on too long and harm motor neurons. Fosigotifator activates a protein called eIF2B to release that brake.

Scientific name: eIF2B (integrated stress response)

Calico announced the HEALEY results on 6 January 2025. Since then the remaining ALS study was terminated and the drug is being developed only for vanishing white matter disease, where the FDA gave it Breakthrough Therapy designation (June 2026) and Europe's EMA gave it PRIME support (October 2026).

Hints only. Controlled trials missed their main goal. Some measures or subgroups looked better, which needs confirming.

Among 310 participants, neither the main dose nor a higher exploratory dose slowed decline on the combined function-and-survival measure compared with placebo, and key secondary measures were also not different. In exploratory analyses at the higher dose, muscle strength declined more slowly (32% in the arms, 62% in the legs), but those numbers were not adjusted for multiple testing and could be chance. The drug was generally safe.

All key studies

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  HEALEY ALS Platform Trial, Regimen FMixed

  2025 · Placebo-controlled · Phase 2/3 · 310 people · Company and academic

  Neither dose slowed decline in function and survival, the main goal. At the exploratory higher dose, muscle strength fell more slowly than on placebo, but this was not the main goal and was not adjusted for testing many measures. We found no full published paper yet.

Results from different trials can't be compared directly. How to read effects

The HEALEY trial was open to people with sporadic or familial ALS. No subgroup was identified that clearly benefited.

How it's taken: Pill taken by mouth

Amylyx is a biotech company in Cambridge, Massachusetts, that developed AMX0035 with ALS researchers at Massachusetts General Hospital. After PHOENIX failed, it removed the drug from the market and restructured the company around other medicines in its pipeline.

Company website ↗

Sodium phenylbutyrate and taurursodiol were each thought to reduce two kinds of stress inside nerve cells: in the endoplasmic reticulum, where proteins are folded, and in the mitochondria, which make energy. The idea was that together they might keep motor neurons alive longer.

Scientific name: Endoplasmic reticulum stress and mitochondrial dysfunction

PHOENIX was meant to confirm the CENTAUR results but showed no benefit after 48 weeks. Amylyx announced it would remove Relyvrio and Albrioza from the market less than a month later. This is one of the clearest examples of a promising smaller trial not holding up in a larger one.

Mixed evidence. At least one controlled trial was positive, but other trials or large independent studies found no benefit.

The earlier CENTAUR trial (137 people, 24 weeks) reported ALSFRS-R decline of 1.24 points a month on the drug versus 1.66 on placebo, with no difference in strength, breathing or survival measures. The much larger PHOENIX trial (664 people, 48 weeks) found no difference from placebo: scores fell 14.98 points on the drug and 15.32 on placebo. Secondary goals, including breathing, quality of life and later survival, also showed no clear difference, including in people who resembled the CENTAUR participants. The PHOENIX result is the more reliable one.

All key studies

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  PHOENIXNo benefit

  2024 · Placebo-controlled · Phase 3 · 664 people · Company-run

  No difference from placebo after 48 weeks on function (0.34 points), on breathing or quality of life, or on later survival, including in CENTAUR-like patients.

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  CENTAUR long-term survival analysisMet its main goal

  2021 · Open-label · Phase 2 · 137 people · Company and academic

  People first given the drug lived a median 6.5 months longer than those first given placebo (most of whom later switched). The EMA judged this survival data unreliable because of how it was collected and analysed.

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  CENTAURMet its main goal

  2020 · Placebo-controlled · Phase 2 · 137 people · Company and academic

  Met its main goal: 2.32 points less ALSFRS-R decline than placebo after 24 weeks. Strength, breathing and other secondary measures did not differ.

Results from different trials can't be compared directly. How to read effects

AMX0035 was tested in adults with definite ALS whose symptoms had started within the previous 18 months, not a specific genetic type. In CENTAUR it was taken once a day for three weeks and then twice a day. It is no longer prescribed for new patients.

How it's taken: By mouth, twice daily

Seelos Therapeutics, a small US biotech, provided trehalose (SLS-005) to the HEALEY trial. Seelos filed for Chapter 11 bankruptcy in November 2024, and GLD Partners bought its assets in October 2025. GLD said it plans to study trehalose in rare neurodegenerative and lysosomal disorders, not specifically ALS.

Company website ↗

Cells clear out damaged and clumped proteins through a recycling process called autophagy. In ALS, this system may not keep up, letting harmful protein clumps build up in motor neurons. Trehalose was thought to switch on autophagy and help clear these clumps.

Scientific name: Autophagy enhancer

Topline results in March 2024 showed no meaningful slowing of ALS. The peer-reviewed paper in May 2025 confirmed this and also found more serious side effects on trehalose than placebo.

Not shown to work. Controlled trials found no benefit.

In the published results (120 people on trehalose, 205 on placebo), the disease rate ratio was 0.87, a possible 13% slowing, but the range of likely values included no effect and the result did not reach the trial's bar for success. Serious side effects were more common on trehalose than on the trial's own placebo group (16% versus 7%). The authors concluded it is unlikely to be effective.

All key studies

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  NIH-funded expanded access studyNo benefit

  2025 · Open-label · 70 people · Independent

  Gave trehalose to 70 people who could not join the trial. It did not change the nerve-damage marker NfL, and decline was no slower than in matched historical patients.

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  HEALEY ALS Platform Trial, Regimen ENo benefit

  2024 · Placebo-controlled · Phase 2/3 · 161 people · Company and academic

  Missed its main goal. A possible 13% slowing did not reach the bar for success, no secondary or biomarker measure improved, and more people had serious side effects on trehalose.

Results from different trials can't be compared directly. How to read effects

The HEALEY trial enrolled adults with ALS at sites across the USA. People in this arm received trehalose (0.75 g per kg of body weight) or placebo as an intravenous infusion once a week for 24 weeks.

How it's taken: IV infusion, weekly

Ferrer is a pharmaceutical company based in Spain. It licensed this oral edaravone formulation (then called TW001) from the Dutch company Treeway in October 2021 and ran the ADORE trial with the European research network TRICALS.

Company website ↗

Like Radicava, FAB122 contained edaravone, which neutralises unstable oxygen molecules (free radicals) thought to damage motor neurons. The idea was that a daily pill would be easier and might work better than on/off cycles of infusions.

Scientific name: Free radical scavenger (antioxidant)

Ferrer and TRICALS announced that FAB122 did not slow ALS progression compared with placebo. Because the trial was large and lasted nearly a year, it gives a clear negative answer for this daily oral formulation.

Not shown to work. Controlled trials found no benefit.

ADORE compared FAB122 100 mg a day with placebo for 48 weeks. Its main goal, slower loss of ALSFRS-R points at 48 weeks, was not met, and there was no benefit on the combined measure of function and survival (CAFS) at 48 or 72 weeks or on other key secondary goals. The drug was safe and well tolerated. Ferrer has not published the size of the difference. This result does not directly test Radicava, which uses a different formulation and dosing schedule.

All key studies

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  ADORENo benefit

  2024 · Placebo-controlled · Phase 3 · 313 people · Company and academic

  Run by Ferrer with the academic network TRICALS in 11 European countries. Daily oral edaravone did not slow decline on the ALSFRS-R over 48 weeks and did not improve survival.

Results from different trials can't be compared directly. How to read effects

ADORE enrolled adults with ALS in 11 European countries. Two in three participants received FAB122 and one in three received placebo, taken by mouth every day for 48 weeks.

How it's taken: Oral, once daily

Cytokinetics is a US biotech company that develops medicines acting directly on muscle. It ran COURAGE-ALS and announced the end of the programme after the results.

Company website ↗

As motor neurons die, the signals reaching muscles weaken. Reldesemtiv binds to troponin, a protein that controls muscle contraction, making fast muscle fibres more sensitive to calcium so they contract more for the same signal. It was meant to ease weakness and fatigue, not to slow the disease itself.

Scientific name: Fast skeletal muscle troponin activator

Cytokinetics announced on March 31, 2023 that the trial had met futility criteria at its second interim analysis and would stop. The full data, presented that December and published in 2025, confirmed no benefit.

Hints only. Controlled trials missed their main goal. Some measures or subgroups looked better, which needs confirming.

In the published Phase 3 results (486 people), the ALSFRS-R score declined 1.1 points more on reldesemtiv than on placebo, a small difference in the wrong direction. A second analysis ranking several outcomes together (a "win ratio") also showed no benefit. Results come from a trial that was stopped early for futility. The earlier Phase 2 trial had missed its main goal too, but trends there led to the Phase 3 trial.

All key studies

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  COURAGE-ALSNo benefit

  2023 · Placebo-controlled · Phase 3 · 486 people · Company-run

  Stopped early for futility. Function scores declined 1.1 points more on reldesemtiv than on placebo over 24 weeks, and no subgroup, including faster progressors, benefited.

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  FORTITUDE-ALSMixed

  2019 · Placebo-controlled · Phase 2 · 458 people · Company-run

  Missed its main goal, breathing capacity after 12 weeks, and function scores also missed. Analyses done afterwards, pooling all doses, suggested about 25% slower loss of function, seemingly larger in faster-progressing people.

Results from different trials can't be compared directly. How to read effects

COURAGE-ALS enrolled adults with ALS in general, not a specific genetic type, at sites in North America, Europe and Australia. Participants took two 150 mg tablets twice a day, or placebo, for 24 weeks, then everyone could take reldesemtiv for another 24 weeks.

How it's taken: Oral, twice daily

Biohaven is a US biotech company focused on brain and nerve diseases. It provided verdiperstat to the HEALEY ALS Platform Trial, which is run by the Healey & AMG Center for ALS at Massachusetts General Hospital.

Company website ↗

Myeloperoxidase is an enzyme made by immune cells that produces harmful oxidising chemicals. In ALS, inflammation in the nervous system may speed up motor neuron damage. Verdiperstat blocks this enzyme in the hope of reducing that inflammation and oxidative stress.

Scientific name: Myeloperoxidase (MPO) inhibitor

Biohaven announced that verdiperstat did not slow ALS compared with placebo. The full peer-reviewed results in 2025 confirmed no effect, and no further ALS trials of verdiperstat have been announced.

Not shown to work. Controlled trials found no benefit.

In the published results (167 people given verdiperstat or its matched placebo), the estimated rate of decline was about the same as placebo (disease rate ratio 0.98, where 1.0 means no difference). Muscle strength and breathing, the key secondary goals, did not improve either. This is a clear negative result.

All key studies

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  HEALEY ALS Platform Trial, Regimen BNo benefit

  2022 · Placebo-controlled · Phase 2/3 · 167 people · Company and academic

  Missed its main goal: decline in function and survival over 24 weeks was the same as on placebo. Muscle strength, breathing and other measures did not differ either.

Results from different trials can't be compared directly. How to read effects

The HEALEY trial enrolled adults with ALS at sites across the USA. People were randomly assigned to one of several drugs being tested, and then to the drug or placebo, taken by mouth twice a day for 24 weeks.

How it's taken: Oral, twice daily

UCB is a Belgian pharmaceutical company focused on immune and neurological diseases. It provided zilucoplan to the HEALEY ALS Platform Trial, run by Massachusetts General Hospital, and sells it as Zilbrysq for myasthenia gravis.

Company website ↗

Complement is a group of immune proteins that can attack and inflame tissue. Some research suggested complement activation may harm motor neurons and the junctions between nerves and muscles in ALS. Zilucoplan blocks C5, a key step in this process.

Scientific name: Complement component 5 (C5) inhibitor

Massachusetts General Hospital announced that the zilucoplan arm had been stopped after an interim review showed it was unlikely to work. The full results, published in 2025, confirmed no benefit.

Not shown to work. Controlled trials found no benefit.

In the published results, 122 people on zilucoplan were compared with 164 on placebo. Decline was, if anything, slightly faster on zilucoplan (disease rate ratio 1.08, where 1.0 means no difference), and the range of likely values included no effect. There was no sign it slows ALS, even though blood tests showed the drug did block complement.

All key studies

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  HEALEY ALS Platform Trial, Regimen ANo benefit

  2022 · Placebo-controlled · Phase 2/3 · 162 people · Company and academic

  Stopped early for futility. Decline in function and survival was slightly faster than on placebo, and investigators saw no subgroup worth testing further.

Results from different trials can't be compared directly. How to read effects

The HEALEY trial enrolled adults with ALS at sites across the USA. In this arm, people injected zilucoplan (0.3 mg per kg) or placebo under the skin every day for 24 weeks.

How it's taken: Injection under the skin, daily

CuATSM was developed by Collaborative Medicinal Development (CMD), a small private company in California that licensed it from the University of Melbourne and ran its trials in Australia. The company's website now says CMD has become Vivat Therapeutics, whose lead drug is for age-related muscle loss, not ALS. We could not find when the rebrand happened.

Company website ↗

CuATSM is a small molecule that carries copper into the brain and spinal cord. The idea was that it releases copper mainly in cells whose mitochondria (energy factories) are failing, helping copper-dependent proteins like SOD1 work properly and mopping up a harmful molecule called peroxynitrite. It worked well in SOD1 mice, but those results did not need to translate to people.

Scientific name: Copper delivery / peroxynitrite

The continuation study of the Phase 2/3 trial is listed as completed on 15 February 2022, the last trial activity we found. No results followed, and as of 2025 the ALS Therapy Development Institute noted results still had not been shared. The company now presents itself as Vivat Therapeutics working on a different drug, and patient organisations list CuATSM as no longer in development.

Early signal only. Only small, open-label or historical-comparison studies so far. Promising at best; not proof.

In the open-label Phase 1 study (32 people, 29 finished), people on the highest dose lost about 0.29 ALSFRS-R points per month, compared with about 1.02 expected from historical records of other patients. There was no placebo group, so this comparison is weak. The placebo-controlled Phase 2/3 trial that should have confirmed or refuted it never reported results. A 2023 study of brain and spinal cord tissue from six treated people who died found no clear protection of nerve cells, though there were fewer inflammatory immune cells (microglia) in the spinal cord.

All key studies

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  Spinal cord and brain tissue from treated patientsNo benefit

  2023 · Post-hoc analysis · 6 people · Independent

  Researchers examined tissue from six trial participants who died. Unlike in mice, CuATSM had no clear effect on motor nerve cell damage or TDP-43 clumps, though there were fewer inflammatory immune cells in the spinal cord.

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  Phase 2/3 CuATSM vs placebo (CMD-2019-001)Pending

  2021 · Placebo-controlled · Phase 2/3 · Company-run

  The only placebo-controlled trial, planned for up to 80 people in Australia, finished in late 2021. The company has never released its results, despite public requests from ALS groups.

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  Phase 2a expansion group (CMD-2016-001)Mixed

  2020 · Open-label · Phase 2 · 15 people · Company-run

  Fifteen more people took the chosen dose. The company reported slow decline and better thinking scores than historical records, again without a placebo group, in a conference abstract only.

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  Phase 1 dose-finding study (CMD-2016-001)Mixed

  2018 · Open-label · Phase 1 · Company-run

  The main goal was finding a safe dose, and CuATSM was well tolerated. People on the chosen dose declined more slowly than historical records predicted, but with no placebo group this comparison is weak.

Results from different trials can't be compared directly. How to read effects

The trials enrolled adults with ALS in Australia, regardless of whether the disease was inherited. CuATSM was taken by mouth once a day.

How it's taken: Pill, daily