Clene Reports Significant Survival Benefit With CNM-Au8® Treatment in ALS EAP Compassionate Use Programs

Rhea-AI Summary

Clene Inc. reports significant survival benefits in ALS patients treated with CNM-Au8 in Expanded Access Programs. The treatment showed a 68% and 57% decreased risk of all-cause mortality compared to controls. The therapy was well-tolerated with no serious adverse events.

Medical Research Analyst

The recent findings from Clene Inc. regarding their 'Compassionate Use' Expanded Access Programs (EAPs) for CNM-Au8 present a significant development in the treatment of amyotrophic lateral sclerosis (ALS). The reported 68% decreased risk of all-cause mortality when compared to PRO-ACT matched controls and a 57% decreased risk when compared to ALS Natural History Consortium matched controls are substantial. These figures suggest that CNM-Au8 could represent a major advancement in ALS therapy, a disease for which treatment options are currently very limited.

From a research perspective, the fact that CNM-Au8 was well-tolerated with no serious adverse events reported is noteworthy. This safety profile, combined with the observed survival benefits, provides a strong rationale for advancing to Phase 3 clinical trials. It is also important to highlight the use of risk-adjusted hazard ratios, which take into account the potential confounders and provide a more accurate measure of the treatment effect.

Furthermore, the use of large and reputable datasets like PRO-ACT and ALS/MND Natural History Consortium for control comparisons adds validity to the results. It is crucial, however, to consider that historical controls have limitations compared to randomized controlled trials. The next phase of research should aim to confirm these results in a randomized setting to rule out any potential biases.

Financial Analyst

The announcement by Clene Inc. regarding the positive results from their EAPs for CNM-Au8 has the potential to positively impact the company's financials. With ALS being a rare and currently under-served medical condition, any successful treatment can command significant market share and pricing power. The movement towards Phase 3 trials is a critical step in the drug development process and can lead to increased investor confidence and potential partnerships or funding opportunities.

Investors will be closely monitoring the progression of CNM-Au8 through the clinical trial pipeline. The success of Phase 3 trials could lead to FDA approval, which would be a significant catalyst for Clene's stock price. However, it is essential to remain cautious, as clinical trials are inherently risky and positive Phase 2 results do not always guarantee success in Phase 3 or regulatory approval.

Considering the current state of the market and investor sentiment towards biopharmaceutical stocks, especially those involved in innovative treatments for rare diseases, Clene Inc. could see increased trading volumes and interest from institutional investors. The long-term outlook will largely depend on the company's ability to maintain its safety profile, demonstrate efficacy in larger trials and navigate the regulatory landscape successfully.

Healthcare Industry Analyst

The data from Clene Inc.'s EAPs for CNM-Au8 could have far-reaching implications for the healthcare industry, particularly in the neurodegenerative disease sector. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, leading to loss of muscle control and eventually death. The current standard of care for ALS includes Riluzole and Edaravone, which only modestly slow disease progression. Thus, the need for more effective treatments is high.

The potential approval and market entry of CNM-Au8 could disrupt the current treatment landscape for ALS. If the Phase 3 trials confirm the EAP results and the drug is approved, it could become part of the standard treatment regimen, offering not just improved quality of life but also extended survival for patients with ALS.

It's also important to consider the broader implications for the neurodegenerative disease market. A successful treatment for ALS could pave the way for research and development into treatments for other similar conditions, such as multiple sclerosis (MS), which Clene is also targeting. This could signify the beginning of a new era in neurodegenerative disease management, with mitochondrial health and neuronal function protection at its core.

• Two “Compassionate Use” Expanded Access Programs (EAPs) provided access to treatment with CNM-Au8 to more than 250 people living with amyotrophic lateral sclerosis (ALS).
  
  
• A significant survival benefit (p=0.0001) was observed in EAP participants treated with CNM-Au8 compared to historical ALS disease progression controls (participants untreated with CNM-Au8) in two independent analyses: a 68% decreased risk of all-cause mortality compared to PRO-ACT matched controls, and a 57% decreased risk of all-cause mortality compared to ALS Natural History Consortium matched controls.
  
  
• CNM-Au8 30 mg treatment was well-tolerated, without a single serious adverse event attributed to CNM-Au8, and no significant safety findings reported.
  

SALT LAKE CITY, Feb. 22, 2024 (GLOBE NEWSWIRE) -- Clene Inc. (Nasdaq: CLNN) (along with its subsidiaries, “Clene”) and its wholly owned subsidiary Clene Nanomedicine, Inc., a clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including ALS and multiple sclerosis (MS), today reported new, significant survival results from two independent analyses of the pooled data from the intermediate-size EAPs supported by Clene. People living with ALS who were generally too advanced in their disease to qualify for clinical trials received daily oral CNM-Au8^® 30 mg for up to four years to date.

A pooled survival analysis of EAP participants treated with CNM-Au8 30 mg was compared to two independent datasets derived from PRO-ACT and the ALS/MND Natural History Consortium. The EAP dataset was comprised of 256 participants with ALS of which 220 EAP participants had all baseline values available for matching. These participants were matched for similar baseline characteristics compared to each non-CNM-Au8 treated control.

The results in the EAP participants versus the matched controls demonstrated a significant survival benefit for each comparison:

• The PRO-ACT dataset is the largest publicly available repository of longitudinal ALS clinical trial data, containing more than 12,000 records of trial participants:
  
  
  • CNM-Au8 EAP vs. PRO-ACT matched controls: The baseline risk-adjusted hazard ratio demonstrated a 68% decreased risk of all-cause mortality with CNM-Au8 treatment (HR: 0.320, 95% CI: 0.178 – 0.575, p = 0.0001).
    
    
• The ALS/MND Natural History Consortium data set contained approximately 1,700 records of people living with ALS from researchers across nine academic sites collecting recent real-world data:
  
  
  • CNM-Au8 EAP vs. ALS/MND Natural History Consortium matched controls: The baseline risk-adjusted hazard ratio demonstrated a 57% decreased risk of all-cause mortality with CNM-Au8 treatment (HR: 0.433, 95% CI: 0.282 – 0.663, p = 0.0001).
    

Analyses including all 256 EAP participants compared to the 220 matched controls also showed statistically significant survival benefits with log-rank p-values of p < 0.0001 and p=0.006 for the PRO-ACT and ALS/MND Natural History Consortium matched controls, respectively.

“The long-term safety and survival data from the CNM-Au8 expanded access programs add to the available data supporting CNM-Au8 moving rapidly to Phase 3 testing in ALS,” said Merit Cudkowicz, MD, MSc, an internationally renowned clinician in the treatment of ALS and Chair of Neurology, Director of the Sean M. Healey and AMG Center for ALS at Mass General Hospital and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “This is one of a few therapies with positive Phase 2 data that must go forward to Phase 3 trials.”

“These EAP results help us better understand how people living with more advanced disease respond to treatment,” said Richard S. Bedlack Jr., MD, PhD, MS Stewart, Hughes and Wendt Distinguished Professor, Neurology, Neuromuscular Disease at Duke University School of Medicine, and a member of the EAP02 steering committee. “Collecting data of peoples’ experience beyond clinical trials is extremely important in rare diseases like ALS. These data warrant consideration to be included in Clene’s discussions about CNM-Au8 with regulatory agencies.”

An EAP is an FDA-regulated pathway that allows patients with a serious or immediately life-threatening condition to gain access to an investigational drug outside of clinical trials when no comparable or satisfactory alternative therapy is available.

The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and Clene supported the first EAP (EAP01) launched in 2019. EAP01 was initiated by Dr. Cudkowicz as the principal investigator. EAP01 is a single-site, intermediate-size EAP that allows individuals with ALS who are otherwise unable to qualify for CNM-Au8 in clinical trials access to CNM-Au8. This is currently the longest running intermediate-size EAP in ALS.

The second EAP (EAP02) was started in 2021 for people living with ALS who did not qualify for participation in the concurrent HEALEY ALS Platform Trial, which is a perpetual multi-center, randomized, double-blind, placebo-controlled clinical trial program designed to evaluate the efficacy and safety of multiple investigational products in people living with ALS. EAP02 is sponsored by Clene and is presently available at 16 clinical sites across the U.S. associated with the Northeast ALS Consortium (NEALS).  

Clene was also part of a consortium that was recently awarded a four-year grant totaling $45.1 million from the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), to conduct a third EAP in ALS. Consortium partners include Synapticure and Columbia University. This EAP is expected to commence enrollment in the first half of 2024.

As previously announced, treatment with CNM-Au8 produced consistent survival and delayed time to ALS clinical worsening data in two independent Phase 2, randomized, placebo-controlled, double-blind ALS trials and their open-label extensions. The Phase 2 HEALEY ALS Platform Trial in the U.S. and the RESCUE-ALS Trial in Australia studied 285 participants with ALS at specialty clinics. CNM-Au8 was well-tolerated in all its clinical studies. No serious adverse events have been associated with CNM-Au8 treatment in any Phase 1 or Phase 2 study conducted, including all those involving ALS participants.

About Clene

Clene Inc., (Nasdaq: CLNN) (along with its subsidiaries, “Clene”) and its wholly owned subsidiary Clene Nanomedicine Inc., is a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson’s disease and multiple sclerosis. CNM-Au8^® is an investigational first-in-class therapy that improves central nervous system cells’ survival and function via a mechanism that targets mitochondrial function and the NAD pathway while reducing oxidative stress. CNM-Au8^® is a federally registered trademark of Clene Nanomedicine, Inc. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please visit www.clene.com or follow us on X (formerly Twitter) and LinkedIn.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor” provisions created by those laws. Clene’s forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this press release and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include our ability to demonstrate the efficacy and safety of our drug candidates; the clinical results for our drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; our ability to achieve commercial success for our drug candidates, if approved; our limited operating history and our ability to obtain additional funding for operations and to complete the development and commercialization of our drug candidates; and other risks and uncertainties set forth in “Risk Factors” in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this press release, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. All information in this press release is as of the date of this press release. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this press release.

Media Contact
Ignacio Guerrero-Ros, Ph.D., or
David Schull
Russo Partners, LLC
Ignacio.guerrero-ros@russopartnersllc.com
David.schull@russopartnersllc.com
(858) 717-2310

Investor Contact
Kevin Gardner
LifeSci Advisors
kgardner@lifesciadvisors.com
(617) 283-2856 

What is the significance of the survival benefit observed in ALS patients treated with CNM-Au8?

The survival benefit observed in ALS patients treated with CNM-Au8 was significant, with a 68% and 57% decreased risk of all-cause mortality compared to controls.

How many people participated in the Expanded Access Programs for CNM-Au8 treatment?

A total of 256 participants with ALS were part of the Expanded Access Programs for CNM-Au8 treatment.

What was the duration of treatment with CNM-Au8 in the EAPs?

Participants received daily oral CNM-Au8 30 mg for up to four years in the Expanded Access Programs.

Who commented on the long-term safety and survival data of CNM-Au8?

Merit Cudkowicz, MD, MSc, an internationally renowned clinician in the treatment of ALS, commented on the long-term safety and survival data of CNM-Au8.

What phase of testing is CNM-Au8 expected to move rapidly to, based on the available data?

CNM-Au8 is expected to move rapidly to Phase 3 testing in ALS based on the available data.