Clene plans CNM-Au8 filing for accelerated approval in ALS
FDA says NfL could potentially serve as surrogate marker
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- Clene plans to seek accelerated FDA approval for CNM-Au8, an experimental ALS therapy.
- CNM-Au8 has been associated with NfL reductions, a biomarker finding linked to longer survival in analyses.
- FDA equested analyses linking the size of NfL reductions to likely clinical benefit.
Following a recent meeting with the U.S. Food and Drug Administration (FDA), Clene is planning to submit an application asking the agency to approve its experimental therapy CNM-Au8 as a treatment for amyotrophic lateral sclerosis (ALS).
The company specifically plans to file a new drug application (NDA) seeking accelerated approval, a pathway that allows the FDA to consider therapies based on a surrogate marker or other early measure that is reasonably likely to predict clinical benefit. This can allow treatments for serious diseases to become available earlier than they normally would, though companies generally must conduct confirmatory studies after approval to verify clinical benefit.
NfL data may support accelerated approval filing
For CNM-Au8, Clene is planning to use biomarker data showing reductions in neurofilament light chain (NfL) levels, a biomarker of nerve damage, and analyses suggesting those reductions are associated with longer survival.
“We are encouraged by the FDA’s careful evaluation of the benefits and risks associated with Clene’s ALS drug candidate, CNM-Au8, including the biomarker data the company provided. The filing of an NDA submission represents an important milestone for CNM-Au8 and for the ALS community,” Rob Etherington, president and CEO of Clene, said in a company press release.
The company expects to have an application ready for submission in the third quarter of 2026.
“People living with ALS cannot afford to wait,” said Sandra Abrevaya, co-founder and board member at the patient-led advocacy group I AM ALS. “Flexible, science-driven regulatory approaches such as this can play a critical role in accelerating access to new therapies for a fast-progressing, fatal disease. We’re grateful for the [FDA]’s recognition of the urgency and unmet need in ALS.”
ALS is a neurodegenerative disorder in which motor neurons, the nerve cells that control movement, become progressively damaged and die.
Motor neurons normally require significant amounts of energy to function, and research suggests that problems with energy production may contribute to motor neuron damage in ALS. CNM-Au8 is an oral suspension of gold nanocrystals designed to support energy production and use in nerve cells, with the goal of improving cell survival and function.
HEALEY analyses suggested possible survival benefit
CNM-Au8 has been tested in an arm (NCT04414345) of the HEALEY ALS platform trial (NCT04297683), an ongoing effort to test several potential ALS treatments in parallel.
That study failed to show that CNM-Au8 was significantly better than a placebo at slowing functional decline, missing its main goal. Nonetheless, exploratory analyses indicated that CNM-Au8 was associated with a reduced risk of death and delayed clinical worsening, with survival benefits also reported in longer-term analyses.
Data from HEALEY ALS and other studies also have indicated that CNM-Au8 was associated with reductions in NfL levels, which was the focus of the discussions with the FDA.
In the recent meeting, the FDA said NfL could potentially serve as a surrogate marker indicating a therapy is reasonably likely to offer clinical benefit for people with ALS. The agency requested, however, that Clene’s application include analyses showing that the magnitude of NfL reduction is reasonably likely to predict clinical benefit. A final decision will depend on the FDA’s review of those data.
The company said it has prepared these analyses and will include them in the upcoming application.
If the FDA decides to grant CNM-Au8 accelerated approval based on the therapy’s effect on NfL levels, Clene would be expected to conduct a confirmatory study to verify clinical benefit, such as longer survival or slower disease progression.
As it gets the application together, the company is also preparing for a confirmatory Phase 3 study, which it plans to begin in early 2027.
“We are committed to working with the [FDA] on this filing and are conducting the Phase 3 confirmatory study for CNM-Au8, which we intend to commence in the first quarter of 2027,” Etherington said.
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