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Atriva Therapeutics receives U.S. FDA Orphan Drug Designation for Zapnometinib to treat Hantavirus Infections

  • 7 min read
  • FDA Orphan Drug Designation (ODD) underscores strength of Atriva’s pipeline and high need for treatments for rare and neglected tropical diseases
  • ODD allows Atriva to benefit from various incentives to develop zapnometinib (ATR-002) against hantavirus infections, and may result in seven-year market exclusivity on approval for this indication
  • Targeting RNA viruses like hantavirus and acting in the host cell, oral drug candidate may provide a beneficial dual antiviral and immunomodulatory effect

Tübingen and Frankfurt, Germany, January 10, 2022 – Atriva Therapeutics GmbH, a biopharmaceutical company pioneering the development of host-targeting antiviral therapies, today announced that its lead candidate zapnometinib (ATR-002) has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of hantavirus infections. These RNA viruses may lead to serious diseases in humans with a high risk of fatality and have been classified by the CDC as a potential bioterrorism agent.[i] Atriva specifically develops first-in-class, host-targeting small molecules that aim to inhibit viral replication and to favorably modulate the body’s immune response to treat severe respiratory diseases induced by RNA viruses.

“Hantavirus infections and the resulting diseases, Hantavirus Pulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome, are potentially life-threatening conditions with no specific treatment to date,” said Prof. Dr. Oliver Planz, CSO of Atriva Therapeutics. “Antiviral efficacy of zapnometinib against hantavirus has been previously proven in vitro in an academic collaboration. With its antiviral, immunomodulating properties as well as its positive safety and tolerability profile, which has been demonstrated already in a Phase I trial, zapnometinib shows the potential to become the first oral drug to specifically treat hantavirus infections.”

Dr. Rainer Lichtenberger, CEO of Atriva Therapeutics, commented: “The Orphan Drug Designation we received for our lead drug candidate zapnometinib is an important milestone towards addressing the urgent needs of patients infected with hantavirus. We are very pleased about this external validation from the FDA and we are looking forward to advancing zapnometinib towards full development in this indication, which is considered an emerging global health threat due to man-made environmental and climatic changes. I am very proud of the excellent scientific research that has yielded convincing results enabling us to progress zapnometinib into this new indication, alongside influenza and COVID-19.”

In humans, hantaviruses, which are usually transmitted by rodents, can cause two different types of severe diseases. Hantavirus Pulmonary Syndrome (HPS) is mainly prevalent throughout the Americas while Hemorrhagic Fever with Renal Syndrome (HFRS) is predominant in Asia and Europe. Both conditions can cause severe lung problems, hemorrhagic fever and death, with fatality rates between 35%[ii] and 50%[iii] for HPS and between 1% and up to 15%[iv] for HFRS, respectively.

Hantaviruses affect around 30,000 people annually[ii] and are emerging as a global health threat, due to environmental changes and ecological alterations that are associated with changing rodent populations and their habitats.[ii],[v],[vi] As of 2019, 816 laboratory-confirmed cases of hantavirus disease have been reported in the U.S. since the start of surveillance in 1993.[vii] ECDC reports more than 4,000 annual cases of HFRS for Europe, and 1,534 for Germany alone in 2019,[viii] whereas annual numbers of HFRS cases are expected to be as high as 150,000, with more than 50% occurring in China.[ix]

To date, neither treatments nor vaccines against HPS or HFRS have yet been made available on a global scale. Therefore, hantavirus infections cause a high unmet medical need.6,[x] The CDC classifies hantaviruses as Category C bioterrorism pathogens that could be engineered for mass dissemination in the future because of its availability; ease of production and dissemination; and potential for high morbidity and mortality rates, as well as a major health impact.[i]

The FDA may grant Orphan Drug Designation (ODD) to support the development and evaluation of new treatments for rare diseases. To give drug companies certain financial benefits for developing orphan drugs that are safe and effective, ODD confers numerous incentives including tax credits for qualified clinical trials, exemption from user fees and potential seven years of market exclusivity in the U.S. on marketing authorization approval.[xi]

About zapnometinib’s mode of action with dual effect

The Atriva lead product zapnometinib (ATR-002) is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. Zapnometinib is a clinical stage MEK inhibitor drug candidate targeting the intracellular Raf/MEK/ERK signaling pathway. Many RNA viruses need to activate this pathway to ensure their replication, such as influenza viruses[xii], hantaviruses[xiii], or the respiratory syncytial virus (RSV)[xiii] , and also coronaviruses[xiii] , including SARS-CoV-2. Zapnometinib inhibits the cellular MEK (MAPK/ERK kinase), blocking the formation of functional virus particles in the host cell, ultimately reducing the viral load in the body.[xiv],[xv] The specific mode of action varies depending on the actual virus type. E.g., in influenza virus infected cells, MEK inhibition blocks the export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm. [xii]

In addition, zapnometinib has the potential to modulate the immune response, thus avoiding an overshooting cytokine/chemokine response that can be caused by viral infections. MEK inhibition can reduce the gene expression of some of the cytokines / chemokines involved, including TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a,[xvi],[xvii] and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID‑19.[xviii]

About Atriva Therapeutics GmbH

Atriva Therapeutics, founded in 2015, is a biopharmaceutical company that is pioneering the development of host-targeting antiviral therapies. It was set up by a team of leading scientists in viral research as well as seasoned industry experts. The company aims to develop a therapy platform to treat severe respiratory and systemic diseases induced by RNA viruses with a high unmet medical need, such as influenza and COVID-19. The Atriva lead product zapnometinib (ATR-002) is a first-in-class, host-targeting agent that aims to inhibit viral replication and to favorably modulate the body’s immune response in RNA viruses. Zapnometinib is under clinical development and has successfully completed a Phase I trial to demonstrate safety and tolerability in healthy subjects. The Company is actively enrolling patients in a Phase II study to evaluate efficacy in hospitalized patients with COVID-19.[xix] A Phase II study in influenza is currently planned, as are further Phase II and III studies in COVID-19. The Company owns 11 patent families with broad international coverage related to the use of MEK inhibitors and other kinase inhibitors for antiviral therapies. The patent life runs through 2041. Atriva Therapeutics is based in Tübingen and Frankfurt, Germany.

Atriva is a founding member of the BEAT-COV initiative. www.beat-cov.de

For further information, please visit www.atriva-therapeutics.com and follow us on LinkedIn and Twitter.

Atriva Therapeutics GmbH

Christian Pangratz
+49 69 999916210


[i]      https://emergency.cdc.gov/agent/agentlist-category.asp

[ii]     Watson DC et al. Crit. Rev Microbiol 2013, 40(3):261-272

[iii]    Zhenqiang B et al. J Infect Dev Ctries 2008; 2(1): 3-23

[iv]    https://www.cdc.gov/hantavirus/hfrs/index.html

[v]     Guterres A et al. One Health 2018, 5:27-33

[vi]    Ferro I et al, PLoS Negl Trop Dis 2020, 14(11): e0008786.

[vii]    https://www.cdc.gov/hantavirus/surveillance/index.html

[viii]   https://www.ecdc.europa.eu/sites/default/files/documents/AER-hantavirus-2019.pdf

[ix]   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863364/pdf/0062-09.pdf

[x]     Muranyi W et al., JASN 2005,12:3669-3679

[xi]    https://www.fda.gov/industry/developing-products-rare-diseases-conditions/designating-orphan-product-drugs-and-biological-products

[xii]    Pleschka S et al. Nat Cell Biol 2001; 3:301-5

[xiii]   Pleschka S, Biol. Chem. 2008; 389:1273-1282

[xiv]   Haasbach E et al. Antiviral Res 2017; 142:178-4

[xv]    Laure M et al. Antiviral Res 2020; 178:104806

[xvi]   Planz O Antiviral Res 2013; 98:457-68

[xvii] Pinto R et al. Antiviral Res 2011; 92:45-56

[xviii] Ragab D et al., Front Immunol 2020; 11: 1446

[xix]   RESPIRE – A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19.