Clene working with FDA on accelerated approval for CNM-Au8
New drug application on track for potential submission at year's end
Clene has incorporated suggestions from the U.S. Food and Drug Administration (FDA) on its analysis plans for certain biomarker data that’s expected to support an accelerated approval application for CNM-Au8 to treat amyotrophic lateral sclerosis (ALS), the company has announced.
Specifically, the FDA had suggested revisions to analysis plans for biomarker data from an expanded access protocol (EAP), or compassionate use program, which allows patients with serious or life-threatening illnesses to access investigational treatments outside of clinical trials when no comparable or satisfactory alternative therapies exist. EAPs can also offer insights about a therapy’s real-world benefits.
Clene has now submitted the revisions to the FDA, with the expectation that regulators will approve the plan in the coming months and the analyses will be performed thereafter.
If the findings are positive, they may support an accelerated approval application by year’s end.
“We are encouraged by the FDA’s collaborative approach and their constructive feedback on our NfL biomarker analysis plan,” Benjamin Greenberg, MD, Clene’s head of medical, said in a company press release.
Meetings with FDA to discuss CNM-Au8 for ALS, MS
Clene has two other meetings planned with the FDA in the next few months, including one to review certain survival data from the HEALEY ALS Platform Trial (NCT04297683), which may also support a regulatory application.
The other meeting is to discuss clinical data related to CNM-Au8’s use in multiple sclerosis (MS).
“With two additional FDA meetings scheduled to discuss long-term ALS survival results and the End-of-Phase 2 MS results, we are advancing our ALS and MS programs to deliver an innovative therapy for people living with neurodegenerative diseases,” Greenberg said.
CNM-Au8 is an oral liquid suspension of gold nanocrystals that’s expected to slow the progression of neurodegenerative diseases by supporting the energetic needs of nerve cells and promoting their survival.
The FDA’s accelerated approval pathway allows regulators to grant conditional marketing authorization for a therapy based on a surrogate clinical trial endpoint that suggests it will lead to a meaningful functional or survival benefit for patients.
While this can enable earlier access to treatment for people with serious or life-threatening illnesses, conversion to a traditional approval still requires confirmatory studies to establish the clinical benefit.
Clene is planning to seek accelerated approval for CNM-Au8 in ALS using data that shows the therapy lowers levels of neurofilament light chain (NfL) — a biomarker of nerve damage that’s linked to ALS progression and survival — and that these changes correlate with clinical benefits for patients.
The FDA has indicated it might consider such an approval based on NfL data, but recommended additional analyses to support the application.
Clene is collecting that data from one of its ongoing EAPs for CNM-Au8 that’s supported by funding from the National Institutes of Health.
Nearly 200 people with ALS have received CNM-Au8 through EAP
Nearly 200 people with ALS have received compassionate use of CNM-Au8 in the EAP, according to Clene.
The planned analyses will evaluate how CNM-Au8 affects NfL levels compared with a matched group of ALS patients from a large database, and will look at how NfL correlates with clinical outcome measures.
After the recent feedback from the FDA, Clene now plans to evaluate the change in NfL levels after nine months of treatment as the primary analysis, and after six months of treatment as a supportive analysis.
The data are expected to confirm findings from the HEALEY trial, which showed CNM-Au8 was associated with reductions in NfL levels. People who experienced NfL reductions saw greater functional and survival benefits than those who did not.
In the upcoming meeting with the FDA, Clene will discuss additional long-term survival data from HEALEY, to ascertain whether it may also support a regulatory application.
A recent analysis compared the survival of people treated with CNM-Au8 in HEALEY to people who received a placebo or the investigational therapy zilucoplan in a separate arm of the study which was stopped early due to lack of efficacy.
Data showed CNM-Au8 significantly extended survival relative to those enrolled in the other trial arm, and were consistent with the survival benefits observed in HEALEY and in the RESCUE-ALS Phase 2 trial (NCT04098406).
The benefits were particularly pronounced in people who met the enrollment criteria for a planned confirmatory Phase 3 trial called RESTORE-ALS, reflective of a population with moderate or severe disease whose symptoms started in the last three years.
Data from RESTORE-ALS could eventually support full approval of CNM-Au8 for ALS, should the results be positive.
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