Early Access to CNM-Au8 Given to Patients Ineligible for HEALEY Trial
Clene, and its wholly owned subsidiary Clene Nanomedicine, have launched an expanded access program (EAP) in the U.S. to allow certain people with amyotrophic lateral sclerosis (ALS) to gain access to its experimental oral therapy CNM-Au8.
Called CNMAu8.EAP02, the program will focus on patients who are not eligible to enroll in the HEALEY ALS Platform Trial (NCT04297683) — the first multi-regimen study in ALS — Clene announced in a press release.
EAPs are meant to make specific investigational therapies — those whose benefits are considered to outweigh their potential risks —available outside the clinical trial setting to people whose serious or life-threatening conditions have few or no adequate treatments.
The HEALY platform trial is currently testing CNM-Au8 and four other potential ALS therapies at the same time to speed development of those found to be most promising, while lowering costs.
Patients for the EAP will be recruited at three of HEALEY’s participating sites, with the collaboration of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, which is leading the trial. The first two sites to be included are the Holy Cross Hospital in Fort Lauderdale, Florida, and the Hospital for Special Care in New Britain, Connecticut.
“We are honored to be collaborating with the Healey Center for ALS in this critically important effort of providing access to CNM-Au8 to people with ALS who may benefit,” said Robert Glanzman, MD, Clene’s chief medical officer.
“The Healey Center is an outstanding partner, and we proudly share its goal of developing lifesaving therapies for the treatment of ALS,” Glanzman added.
Notably, CNMAu8.EAP02 represents Clene’s second EAP for ALS, with the first, named CNMAu8.EAP01 (NCT04081714), currently providing 40 patients early access to CNM-Au8. Launched in 2019, also in partnership with the Healey Center for ALS, the initial program includes patients who have been treated for up to two years.
Problems in mitochondria, the cell’s powerhouses, as well as oxidative stress, have been associated with several neurodegenerative diseases, including ALS. Oxidative stress is an imbalance between the production of harmful free radicals — that occurs mostly in mitochondria — and cells’ ability to detoxify them.
CNM-Au8 is a stable suspension of pure gold nanocrystals designed to increase energy production, while protecting cells against oxidative stress.
Importantly, the therapy can cross the blood-brain barrier, the highly selective membrane that prevents circulating microbes and potentially harmful molecules from reaching the central nervous system, or CNS, comprised of the brain and spinal cord. The blood-brain barrier is a common obstacle for treatments targeting the CNS, preventing their usefulness.
As such, CNM-Au8 is expected to prevent nerve cell death and slow disease progression in ALS patients.
Previous preclinical studies showed that CNM-Au8 improved nerve cell survival and motor neuron function in rodent models of ALS and other neurodegenerative diseases, such as Parkinson’s disease and multiple sclerosis.
The therapy’s safety, pharmacokinetics, pharmacodynamics, and effectiveness were evaluated in 45 adults with early ALS who enrolled in the recently completed, Australian-based Phase 2 RESCUE-ALS trial (NCT04098406). Pharmacokinetics refers to a therapy’s movement into, through, and out of the body, while pharmacodynamics refers to how it affects the body.
Unblinded top-line results are expected in the upcoming months. Interim blinded results suggest that the therapy may, to some degree, slow ALS progression relative to its natural course, but it remains unknown whether the observed benefits come from patients given CNM-Au8 or from those on a placebo.
Also, a U.S.-based Phase 2 trial, called REPAIR-ALS (NCT03843710), is set to assess CNM-Au8’s metabolic effects in the CNS of up to 24 ALS patients. The study may not yet be recruiting.
Within HEALEY, the CNM-Au8’s pivotal Phase 2/3 trial arm (NCT04414345), which reached 50% of its target enrollment in March, will include up to 160 adults with sporadic or familial ALS. Participants will be randomly assigned to drink two bottles of either 30 or 60 mg of CNM-Au8 (120 patients) or a placebo (40 patients), daily for 24 weeks, or about six months.
HEALEY’s shared goals include changes in disease progression — as assessed with the ALS Functional Rating Scale-Revised — lung function, muscle strength, and survival, as well as safety measures.
Recruitment for CNM-Au8 and other trial arms is ongoing at more than 50 sites across the U.S.; more information can be found here.
Top-line results from the CNM-Au8 arm are expected by mid-2022. Should they be positive, Clene plans to use them to support regulatory submissions seeking the therapy’s approval for ALS.
“While CNM-Au8 advances through the registration platform trial with an aim to become available to all patients with ALS, expanded access programs enable more people with ALS to benefit today from the potential of our first-in-class neuroreparative energetic nanotherapeutic,” said Rob Etherington, Clene’s president and CEO.
“Clene is committed to supporting communities living with devastating neurodegenerative diseases, and we are doing our utmost each day to reach and treat more patients,” Etherington added.
In August, the company announced the completion of two lease agreements that will more than quadruple its capacity to manufacture CNM-Au8.