EU Committee Urges Orphan Drug Status for Clene’s CNM-Au8 for ALS

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by Vanda Pinto, PhD |

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Orphan drug status has been recommended in the EU for Clene Nanomedicine’s CNM-Au8, an oral therapy candidate for amyotrophic lateral sclerosis (ALS), by a committee of the European Medicines Agency (EMA).

CNM-Au8 is emerging as a promising treatment for the progressive neurodegenerative condition, with the most recent trial data showing the compound reduced the risk of death by 70% compared with a placebo. The therapy also has been found to significantly extend the time to disease progression in people with ALS.

The European Commission now will decide whether or not to grant the designation, using this positive opinion from the EMA’s Committee for Orphan Medicinal Products (COMP).

In Europe, orphan drug status is given to promising therapies for serious and life-threatening conditions affecting no more than one in every in 2,000 people, and for which the experimental medicine is showing significant benefit over existing therapies. A similar designation can be awarded in the U.S. for therapies for rare diseases or conditions affecting fewer than 200,000 people.

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EU Committee Urges Orphan Drug Status for Clene’s CNM-Au8 for ALS

If granted, EU orphan drug status will provide Clene with several incentives intended to speed CNM-Au8’s clinical development and regulatory review, including assistance with trial protocols, reduced regulatory fees, and a 10-year market exclusivity period upon approval.

“It is extremely gratifying to receive orphan drug designation in the European Union for the treatment of ALS with CNM-Au8,” Rob Etherington, president and CEO of Clene, said in a company press release.

“We plan to make CNM-Au8 broadly available to patients with this rapidly progressive neurodegenerative disease as soon as possible, and we look forward to working with the European Medicines Agency to advance toward this goal,” Etherington said.

CNM-Au8 is a liquid suspension of gold nanocrystals that enters the brain and improves nerve cell survival and function. It does so by supporting the cells’ energy needs and providing protection against oxidative stress, a type of cell damage that occurs in ALS and other neurodegenerative diseases.

Preclinical studies in rodent models of ALS showed that CNM-Au8 protects motor neurons — the nerve cells responsible for voluntary movement, which are progressively lost in ALS — from severe damage and death.

COMP’s positive opinion was based on data from preclinical studies in ALS models and from the RESCUE-ALS Phase 2 trial (NCT04098406) and its open-label extension (OLE) study (NCT05299658)

CNM-Au8 in clinical trials

Based in Australia, RESCUE-ALS investigated CNM-Au8’s safety and effectiveness in adults with early ALS. The trial also evaluated the therapy’s pharmacokinetics — its movement into, through, and out of the body — and pharmacodynamics, or its effects on the body.

A total of 45 patients were randomly assigned to either 30 mg of CNM-Au8 or a placebo, taken daily by mouth, for about nine months. Neither the participants nor the researchers knew which patients were receiving the therapy and which the placebo. Those receiving a stable dose of riluzole, an approved ALS therapy sold as Rilutek, Tiglutik, and Exservan, were able to continue that treatment during the trial.

After this phase, participants had the option to enter the OLE study, in which all are receiving the treatment for up to two years.

The study’s main goal was to assess changes in the number, health, and function of motor neurons using the MUNIX(4) sum, an established predictor of clinical decline. As secondary and exploratory goals, researchers evaluated changes in lung function, ability to perform activities of daily life, and quality of life.

Although the study initially failed to show that CNM-Au8 could prevent motor neuron loss and lung function decline, additional analyses indicated that it significantly slowed disease progression and improved quality of life compared with a placebo.

The company recently announced long-term survival data from RESCUE-ALS participants who either chose to enter its OLE study or decided not to and whose health status was captured when possible.

Five of the 22 patients (22.7%) in the CNM-Au8 group died versus 14 of the 21 patients (66.7%) originally assigned to the placebo. Statistical analyses showed that patients taking CNM-Au8 from the start of the RESCUE-ALS trial had a 70% lower risk of death compared with those who received the placebo.

Additionally, the treatment was found to be generally well-tolerated and safe in the long term.

“We are extremely encouraged by the recent statistically significant survival benefit demonstrated by CNM-Au8 in the long-term open-label extension of the RESCUE-ALS trial,” Etherington said.

CNM-Au8’s safety and effectiveness also are being evaluated in the HEALEY ALS platform trial (NCT04297683), which is testing several potential ALS therapies simultaneously.

A total of 160 adults with sporadic or familial ALS have been enrolled in CNM-Au8’s Phase 2/3 trial arm (NCT04414345), and were randomly assigned to receive either 30 or 60 mg of CNM-Au8 or a placebo, to take daily for about six months.

The company is expecting top-line data from this trial in the coming months. Should the findings be positive, Clene plans to use them to support regulatory filings seeking the therapy’s approval for ALS.