New analyses in ALS planned to aid CNM-Au8’s accelerated approval
Joint effort with APST Research will explore therapy's effect on NfL levels
Clene is collaborating with APST Research to further explore how CNM-Au8 affects levels of neurofilament light chain (NfL) among amyotrophic lateral sclerosis (ALS) patients being treated in expanded access programs (EAPs).
The joint effort is intended to support the accelerated approval of CNM-Au8 for ALS, which Clene intends to seek based largely on clinical trial data related to NfL, an established nerve damage biomarker that’s associated with ALS progression.
The U.S. Food and Drug Administration (FDA) indicated in December that it might consider approving the therapy based on such data, but recommended the additional analyses to support NfL as an adequate outcome measure.
As part of the analyses, NfL changes in EAP participants given CNM-Au8 will be compared with matched untreated participants from APST’s ALS database, which contains long-term NfL and clinical outcome data from thousands of patients.
The company will submit its plans to the FDA soon and is expected to file for CNM-Au8’s accelerated approval in the second half of this year, buoyed by the data that will be generated.
“We are excited to enter into this endeavor with one of the world’s largest ALS NfL datasets in order to supplement available biomarker NfL data from our … EAP, and to support the existing clinical study data for the potential review of an application for approval of CNM-Au8 in ALS via an accelerated regulatory pathway,” Rob Etherington, Clene president and CEO, said in a company press release.
Accelerated approval enables the FDA to grant conditional marketing authorization for a therapy based on a surrogate clinical trial endpoint that suggests it will likely be of clinical benefit. Conversion to a full, traditional approval requires confirmatory studies to establish this benefit. For the FDA to consider a biomarker like NfL an adequate surrogate endpoint that supports accelerated approval, there must be adequate data showing that changes in the biomarker correlate meaningfully with patients’ clinical outcomes.
Regulators initially indicated that NfL biomarker data from CN-Au8 clinical trials wouldn’t be enough to support an accelerated approval, but the FDA changed its position after a November meeting with Clene where the company provided more data.
Exploring CNM-Au8’s impact on NfL levels
Data from Phase 2 trials, including the HEALEY ALS Platform Trial (NCT04297683), have shown that CNM-Au8, an oral liquid suspension of gold nanocrystals, leads to reductions in NfL levels, and that these decreases may be associated with improved survival and slower disease progression.
EAPs, also called compassionate use programs, are designed to enable patients access to experimental therapies outside of clinical trials. They also can offer more information about a therapy’s real-world effects.
Clene has launched three EAPs of CNM-Au8 for ALS patients, one of which received a four-year grant from the National Institutes of Health (NIH) totaling $45 million, with nearly 500 people treated so far. Data from the EAPs have further demonstrated CNM-Au8’s potential for extending ALS survival.
The planned analyses will explore CNM-Au8’s impact on NfL levels in ALS participants enrolled in the NIH-sponsored EAP and will leverage data contained in APST’s database. One of the largest of its kind, the repository contains clinical and demographic information from thousands of ALS patients, as well as long-term NfL data.
“Our extensive and robust data collection empowers pharmaceutical companies to advance their clinical research and trials, driving us toward a deeper understanding of ALS disease progression,” said Thomas Meyer, MD, APST founder and CEO.
Clene’s analysis will involve NfL data from more than 1,625 ALS patients. It aims to compare changes in NfL experienced by CNM-Au8-treated EAP participants with matched patients from the APST database.
NfL data will also be correlated with clinical outcome measures, including those related to disease progression and lung function. Another objective of the analyses is to demonstrate that the rate of NfL change is associated with survival in ALS, backing the use of the biomarker as a surrogate endpoint.
Clene also plans a Phase 3 trial called RESTORE-ALS, which would help definitively establish if CNM-Au8 extends survival in ALS patients. The company has indicated plans to launch the trial this year.
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