Clene seeks FDA accelerated approval of oral ALS treatment

Clene Nanomedicine has submitted an application to the U.S. Food and Drug Administration (FDA) seeking accelerated approval of its experimental oral therapy CNM-Au8 for people with amyotrophic lateral sclerosis (ALS).

The new drug application (NDA), submitted earlier this month, is supported mainly by clinical data suggesting that CNM-Au8 can lower blood levels of neurofilament light chain (NfL), a well-established marker of nerve damage, in ALS patients, along with analyses linking NfL reductions to longer survival.

“The submission of our NDA for CNM-Au8 represents an important achievement for Clene, CNM-Au8, and especially for people living with ALS,” Rob Etherington, president and CEO of Clene, said in a company press release. “Reaching this stage reflects years of dedicated work by the Clene team, our clinical investigators, patients and families, and our partners.”

FDA’s accelerated approval pathway allows promising treatments to be marketed based on preliminary evidence showing they are reasonably likely to predict clinical benefit. Full approval is dependent on additional clinical trial data confirming a therapy’s efficacy.

Clene is preparing such a confirmatory Phase 3 clinical trial, to be named RESTORE-ALS. The main goals will be to determine whether CNM-Au8 can extend survival and delay clinical worsening events relative to a placebo in people with ALS.

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“We remain focused on advancing CNM-Au8 through the regulatory process as efficiently as possible while continuing our preparations for the confirmatory Phase 3 RESTORE-ALS study,” Etherington said. “People living with ALS urgently need additional treatment options, and we believe CNM-Au8 has the potential to restore and protect neuronal health and function and improve survival.”

ALS is a neurological disease that damages motor neurons, the specialized nerve cells that control movement. As these cells are progressively damaged and die, people experience worsening muscle weakness and difficulties walking, speaking, swallowing, and breathing.

CNM-Au8 is an oral liquid containing nanocrystals, tiny gold particles designed to support nerve cells’ energy needs and boost their survival. Nerve cells (neurons) require large amounts of energy to function properly, and problems with energy production are thought to contribute to the progression of ALS and other neurological diseases.

Clene’s application draws on findings from the Phase 2 RESCUE-ALS trial (NCT04098406) and the CNM-Au8 arm (NCT04414345) of the HEALEY ALS platform trial (NCT04297683), which is evaluating several potential ALS therapies simultaneously to speed their development. The NDA also includes findings of subsequent trial data analyses linking reductions in NfL to better clinical outcomes.

Although neither trial met its main goal, RESCUE-ALS data suggested that CNM-Au8 could slow disease progression and extend survival relative to a placebo in people with ALS. HEALEY data also pointed to a lower risk of death and delayed clinical worsening, alongside reductions in blood NfL levels.

Encouraged by these findings, Clene began pursuing accelerated approval, but the FDA initially considered the available evidence insufficient. The agency outlined a possible path forward after Clene presented additional data.

These included new findings from HEALEY linking lower blood NfL levels in CNM-Au8-treated patients to a 65% lower risk of death compared with treated patients who did not show NfL reductions.

In addition, data from an expanded access program (EAP), which provides access to experimental therapies outside clinical trials, showed that CNM-Au8 treatment reduced blood NfL levels in ALS patients.

In both HEALEY and the EAP, the therapy also lowered blood levels of glial fibrillary acidic protein, a marker of damage to cells that support neurons. Patients with the greatest reductions in these two biomarkers tended to have the longest survival times.

More recently, additional analyses conducted to address FDA concerns showed that HEALEY participants whose NfL levels declined or remained stable with CNM-Au8 had a 38% lower risk of death than those assigned to a placebo or other experimental treatments in HEALEY that failed to show benefits.

These findings provided further support using NfL as a surrogate outcome, or a measure expected to predict a treatment’s clinical benefits, in Clene’s application seeking CNM-Au8’s accelerated approval. With the NDA submitted, the FDA will first decide whether to accept it for review and, ultimately, whether to grant accelerated approval.