- In a simulation of 200 virtual subjects, a single dose of GV104 (16 mg nalmefene buccal film) taken at least 15 minutes before exposure prevented every potential fentanyl-induced cardiac arrest, at intravenous fentanyl doses known to be lethal in humans -
- FDA re-affirmed the overall approach and provided comments that will improve the Company's ability to "demonstrate long-term prophylactic protection" -
- The FDA comments are an important step in the path leading to an NDA. The Company intends to submit its response promptly -
RED BANK, NJ / ACCESS Newswire / October 26, 2026 / Hepion Pharmaceuticals, Inc. (OTCQB:HEPA) ("Hepion" or the "Company"), a biotechnology company developing therapeutic and diagnostic candidates for areas of high unmet medical need, today reported results from an expanded modeling and simulation analysis of GV104, conducted by its wholly-owned subsidiary Gravitas Life Sciences, LLC ("GLS"), and the written feedback received from the U.S. Food and Drug Administration ("FDA" or "Agency"). The simulation modelled lethal fentanyl doses. In the simulations, a single 16 mg GV104 buccal film taken at least 15 minutes before exposure prevented every simulated fentanyl-induced cardiac arrest. The Agency's responses provided suggestions the Company believes it can address within its existing modeling program.
GV104 is a buccal film of the opioid antagonist nalmefene, in development as a prophylactic countermeasure for military personnel and first responders who may be exposed to high-potency opioids, including weaponized fentanyl and its analogues. Submitted to the FDA in July 2026, the analysis combines population pharmacokinetics with a physiological model of opioid overdose. The model was developed by FDA researchers, and widened with data from the published literature. This model used GV104 nalmefene population pharmacokinetics to predict fentanyl-induced cardiac arrest. Lethal fentanyl doses, roughly two to seven times those used for pain relief, were used in the model. As this product is intended to be used by military personnel and first responders, the company also modeled the use of GV104 in humans with athletic body composition (high lean-body-mass).
Complete protection in the simulated challenge. At the highest dose modeled, 86.5 percent of untreated simulated subjects were expected to develop cardiac arrest. In simulations of 200 virtual subjects, at all fentanyl doses modelled, a single GV104 16 mg film taken 15 minutes or more before exposure, prevented every simulated cardiac arrest. Similar results were observed in simulated individuals with high lean-body-mass.
Rapid predicted onset. The model predicts that GV104 achieves protection against fentanyl exposure at a median of 10 to 15 minutes after dosing, compared to roughly 30 minutes initially estimated in 2025.
FDA Feedback and Path Forward
In written responses to the Company's July 2026 briefing package, the agency re-affirmed the overall approach. Specifically, the FDA commented on the model structure, the presentation of results, and the fentanyl challenge simulations, stating that incorporating these comments and revising the simulations will improve the Company's position to demonstrate long-term prophylactic protection of the product.
The Company believes each comment is addressable within its existing modeling program and intends to submit its response promptly. Until then, the results described here should be understood as the output of the analysis as submitted in July 2026, and the predicted onset, duration and degree of protection may change. GV104 is being developed as a 505(b)(2) New Drug Application relying in part on the FDA's prior findings for an approved injectable product; in March 2025 the FDA stated that "additional clinical studies do not appear to be necessary to define the prophylactic dosing window at this time." The principal remaining work before a filing is the Chemistry, Manufacturing and Controls program and the commercial-scale registration batches the Company intends to begin producing in 2027.
Addressing a National Security Need
High-potency synthetic opioids are recognized as a national security threat, and personnel entering a contaminated area need protection they can carry in with them. An injectable naloxone product approved in February 2022 carried both an emergency treatment and a temporary prophylaxis indication for this population; however it is currently listed as discontinued in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations. Other approved opioid antagonists are indicated only for emergency use after exposure. GV104 is being developed as a buccal film that can be taken before entering a contaminated area, with a longer predicted duration of protection.
About GV104
GV104 is an investigational transmucosal buccal film of nalmefene, an opioid receptor modulator that acts as an antagonist at the mu and delta opioid receptors and a partial agonist at the kappa receptor; it has not been approved by the FDA or any other regulatory authority for any indication. Nalmefene was first approved in the United States in 1995 and is marketed in injectable and nasal spray formulations for opioid overdose and the reversal of opioid effects. Delivered across the buccal mucosa, the film potentially bypasses first-pass hepatic metabolism, and GLS holds an exclusive, sublicensable, worldwide license to the relevant patent rights and technology. GLS is developing GV104 through a 505(b)(2) regulatory pathway for the temporary prophylaxis against high-potency opioid exposure in military personnel and chemical incident responders. The Company is also developing GV104 for pathologic gambling disorder through a similar regulatory pathway.
About Hepion Pharmaceuticals
Hepion Pharmaceuticals, Inc. (OTCQB:HEPA) is a biotechnology company developing therapeutic and diagnostic candidates for areas of high unmet medical need. Through its subsidiary Gravitas Life Sciences, LLC, a clinical-stage biotechnology company, Hepion is advancing therapeutic candidates including a transmucosal buccal film of an established opioid antagonist and an oral formulation of a validated anti-inflammatory antibody. The Company's diagnostic program is built on novel circulating tumor RNA technology, which reads actively expressed tumor transcripts for the early detection of hepatocellular carcinoma in high-risk cirrhotic patients, a cancer that is curable when found early. For more information please visit: https://hepionpharma.com/.
Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, are forward-looking statements, including statements regarding the results and interpretation of the Company's modeling and simulation analyses, the predicted onset and duration of protection, the Company's belief that the FDA's comments are addressable within its existing modeling program, the Company's plans to address the FDA's October 2026 written responses and the expected content, timing and results of any revised analysis, the Company's interpretation of FDA feedback and the 505(b)(2) regulatory pathway for GV104, the Chemistry, Manufacturing and Controls work and registration batches required before a New Drug Application, the timing and content of future regulatory submissions and communications, the availability of capital to fund the program, and the Company's strategy, future operations, future financial position, projected costs, prospects, plans and objectives of management. Words such as "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Modeling and simulation results are predictions generated from mathematical models and the assumptions built into them; they are not clinical outcomes, they may not be predictive of results in humans, and regulatory authorities may disagree with the models, the assumptions or the conclusions drawn from them. The results described in this release are from the analysis as submitted to the FDA in July 2026; the Agency has asked the Company to revise aspects of that analysis, the revised analysis may produce different results, and there can be no assurance that the Company will be able to address the Agency's comments, that it will do so within the timeframe it intends, or that the Agency will be satisfied with the Company's responses. Feedback previously received from the FDA is advisory, is not binding on the Agency, and the Agency may change its views at any later stage of development. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, actual results or events could differ materially from them, and you should not place undue reliance on them. Factors that may cause such differences include, but are not limited to, those discussed under Risk Factors set forth in the Company's Annual Report on Form 10-K for the year ended December 31, 2025 and other periodic reports filed with the Securities and Exchange Commission. These forward-looking statements represent the Company's views as of the date of this release and should not be relied upon as representing its views as of any subsequent date; the Company does not undertake and specifically disclaims any obligation to update or revise them, except as may be required by applicable law.
Contacts:
Hepion Investor Relations
ir@hepionpharma.com
https://hepionpharma.com/
SOURCE: Hepion Pharmaceuticals, Inc.
View the original press release on ACCESS Newswire:
https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/hepion-pharmaceuticals-receives-fda-feedback-supporting-a-path-to-dem-1241481
