Peramivir

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Peramivir
Peramivir.svg
Clinical data
Trade names Rapivab
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (IV)
Elimination half-life 7.7 to 20.8 hours (in patients with normal renal function)
Excretion Kidney
Identifiers
  • (1S,2S,3R,4R)-3-[(1S)-1-(Acetylamino)-2-ethylbutyl]-4-(carbamimidoylamino)-2-hydroxycyclopentanecarboxylic acid
CAS Number
PubChem CID
DrugBank
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UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H28N4O4
Molar mass 328.413 g·mol−1
3D model (JSmol)
  • CCC(CC)[C@@H]([C@H]1[C@@H](C[C@@H]([C@H]1O)C(=O)O)NC(=N)N)NC(=O)C
  • InChI=1S/C15H28N4O4/c1-4-8(5-2)12(18-7(3)20)11-10(19-15(16)17)6-9(13(11)21)14(22)23/h8-13,21H,4-6H2,1-3H3,(H,18,20)(H,22,23)(H4,16,17,19)/t9-,10+,11+,12-,13+/m0/s1 X mark.svgN
  • Key:XRQDFNLINLXZLB-CKIKVBCHSA-N X mark.svgN
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Peramivir (trade name Rapivab) is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. It is approved for intravenous administration. [1]

Contents

In October 2009, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the use of peramivir based on safety data from phase I, phase II, and limited phase III trial data. The emergency use authorization for peramivir expired in June 2010. [2] [3] On 19 December 2014, the FDA approved peramivir to treat influenza infection in adults. [1]

History

An intramuscular (IM) peramivir phase II study for seasonal influenza in 2008–2009 found no effect for the primary endpoint of improvement in the median time to alleviation of symptoms in subjects with confirmed, acute, uncomplicated influenza infection versus placebo.[ citation needed ]

In October 2009, it was reported that the experimental antiviral drug peramivir had been "life-saving" effective in intravenous treating 8 serious cases of swine flu. [4] On October 23, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization for peramivir, allowing the use of the drug in intravenous form for hospitalized patients only in cases where the other available methods of treatment are ineffective or unavailable; [5] for instance, if oseltamivir resistance develops and a person is unable to take zanamivir via the inhaled route. The U.S. government (department of Health and Human Services) gave BioCryst Pharmaceuticals more than $77 million to finish the Phase III clinical development of peramivir. In 2009 the department of Health and Human Services had already given about $180 million to the program. [6] Biocryst also donated 1200 courses of treatment to the US department of Health and Human Services. [7] The Emergency Use Authorization expired on June 23, 2010. In 2011 a phase III trial found the median durations of influenza symptoms were the same with 1 intravenous injection of peramivir against 5 days of oral oseltamivir for people with seasonal influenza virus infection. [8]

In 2012 BioCryst reported that it should halt enrollment on its study for intravenous peramivir in potentially life-threatened people after an interim analysis led trial monitors to conclude that it would be futile to continue and the trial should be terminated. The difference between peramivir and control group (oral oseltamivir) for the primary endpoint, clinical or virologic, was small. [9] In 2013 the Biomedical Advanced Research and Development Authority (BARDA/HHS) released new funding under the current $234.8 million contract to enable completion of a New Drug Application filing for intravenous (IV) peramivir. [10]

According to a research report published in June 2011, a new variant of swine flu had emerged in Asia with a genetic adaptation (a S247N neuraminidase mutation) giving some resistance to oseltamivir and zanamivir, but no significant reduction in sensitivity to peramivir. [11] [12] But a H274Y virus mutation showed resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 neuraminidases. [13] Ultimately 3.2% (19/599) of A(H1N1)pdm09 viruses collected between 2009 and 2012 had highly reduced peramivir inhibition due to the H275Y NA mutation. [14]

BioCryst Pharmaceuticals submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for intravenous peramivir in December 2013. [15] Peramivir (Rapivab) was approved for intravenous administration in December 2014. [1] [16]

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees.

<span class="mw-page-title-main">Zanamivir</span> Influenza medication

Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is marketed by GlaxoSmithKline under the trade name Relenza as a powder for oral inhalation.

<span class="mw-page-title-main">Oseltamivir</span> Antiviral medication used against influenza A and influenza B

Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.

<span class="mw-page-title-main">Amantadine</span> Medication used to treat dyskinesia

Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to widespread drug resistance. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist. The antiviral mechanism of action is antagonism of the influenzavirus A M2 proton channel, which prevents endosomal escape.

<span class="mw-page-title-main">Neuraminidase</span> Glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids

Exo-α-sialidase is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:

Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.

<span class="mw-page-title-main">Influenza treatment</span> Therapy and pharmacy for the common infectious disease

Treatments for influenza include a range of medications and therapies that are used in response to disease influenza. Treatments may either directly target the influenza virus itself; or instead they may just offer relief to symptoms of the disease, while the body's own immune system works to recover from infection.

Rintatolimod, sold under the tradename Ampligen, is a medication intended for treatment of chronic fatigue syndrome (CFS). There is some evidence it may improve some CFS symptoms.

<span class="mw-page-title-main">Nitazoxanide</span> Chemical compound

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Influenza</span> Infectious disease, often just "the flu"

Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">Viral neuraminidase</span>

Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.

An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, including by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), as codified by 21 U.S.C. § 360bbb-3, to allow the use of a drug prior to approval. It does not constitute approval of the drug in the full statutory meaning of the term, but instead authorizes the FDA to facilitate availability of an unapproved product, or an unapproved use of an approved product, during a declared state of emergency from one of several agencies or of a "material threat" by the Secretary of Homeland Security.

An antiviral stockpile is a reserve supply of essential antiviral medications in case of shortage. Many countries have chosen to stockpile antiviral medications against pandemic influenza. Because of the time required to prepare and distribute an influenza vaccine, these stockpiles are the only medical defense against widespread infection for the first six months. The stockpiles may be in the form of capsules or simply as the active pharmaceutical ingredient, which is stored in sealed drums and, when needed, dissolved in water to make a bitter-tasting, clear liquid.

BioCryst Pharmaceuticals, Inc. is an American pharmaceutical company headquartered in Durham, North Carolina. The company is a late stage biotech company that focuses on oral drugs for rare and serious diseases. BioCryst's antiviral drug peramivir (Rapivab) was approved by FDA in December 2014. It has also been approved in Japan, Korea, and China.

<span class="mw-page-title-main">Laninamivir</span> Chemical compound

Laninamivir (CS-8958) is a neuraminidase inhibitor that is a drug used for the treatment and prophylaxis of Influenzavirus A and Influenzavirus B. It is currently in Phase III clinical trials. It is a long-acting neuraminidase inhibitor administered by nasal inhalation.

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Margaret Tisdale was a Welsh-born clinical virologist known for her studies of antiviral resistance in HIV and influenza virus, and for coordinating the development of the anti-influenza drug zanamivir.

<span class="mw-page-title-main">Baloxavir marboxil</span> Antiviral medication

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<span class="mw-page-title-main">Pimodivir</span>

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<span class="mw-page-title-main">Molnupiravir</span> Antiviral medication

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID-19 in those infected by SARS-CoV-2. It is taken by mouth.

References

  1. 1 2 3 "Drug Approval Package: Rapivab (peramivir) Injection NDA #206426". U.S. Food and Drug Administration (FDA). 16 January 2015. Retrieved 11 February 2020.
  2. ↑ Thorlund K, Awad T, Boivin G, Thabane L (May 2011). "Systematic review of influenza resistance to the neuraminidase inhibitors". BMC Infectious Diseases. 11 (1): 134. doi:10.1186/1471-2334-11-134. PMC   3123567 . PMID   21592407.
  3. ↑ "Peramivir authorized for Emergency use". LifeHugger. 2009-12-04. Archived from the original on 2011-07-13. Retrieved 2009-12-04.
  4. ↑ "Life-Saving H1N1 Drug Unavailable to Most". CBS Evening News. Atlanta, GA, USA: CBS Interactive. 2009-10-19. Retrieved 2009-10-20.
  5. ↑ "Emergency Use Authorization Granted For BioCryst's Peramivir". Reuters. 2009-10-24. Archived from the original on 2009-10-27.
  6. ↑ "Feds hand BioCryst $77M for anti-viral trial". Fierce biotech. September 21, 2009.
  7. ↑ "FDA Authorizes Emergency Use of Intravenous Antiviral Peramivir for 2009 H1N1 Influenza for Certain Patients, Settings". Reuters. 2009-10-24. Archived from the original on 2009-10-27.
  8. ↑ Kohno S, Yen MY, Cheong HJ, Hirotsu N, Ishida T, Kadota J, et al. (November 2011). "Phase III randomized, double-blind study comparing single-dose intravenous peramivir with oral oseltamivir in patients with seasonal influenza virus infection". Antimicrobial Agents and Chemotherapy. 55 (11): 5267–76. doi:10.1128/AAC.00360-11. PMC   3195028 . PMID   21825298.
  9. ↑ "BioCryst scraps $235M late-stage flu drug program backed by feds". Fierce Biotech. November 8, 2012.
  10. ↑ "BioCryst to File Peramivir NDA Supported by BARDA/HHS Funding". Fierce Biotech. July 11, 2013.
  11. ↑ Hurt, A.C. (9 June 2011). "Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation". Eurosurveillance.
  12. ↑ Hirschler, Ben (2011-06-10). "Swine flu starting to show resistance to drugs". Reuters.
  13. ↑ McKimm-Breschkin JL (January 2013). "Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance". Influenza and Other Respiratory Viruses. 7 Suppl 1: 25–36. doi:10.1111/irv.12047. PMC   4942987 . PMID   23279894.
  14. ↑ Leang SK, Kwok S, Sullivan SG, Maurer-Stroh S, Kelso A, Barr IG, Hurt AC (March 2014). "Peramivir and laninamivir susceptibility of circulating influenza A and B viruses". Influenza and Other Respiratory Viruses. 8 (2): 135–9. doi:10.1111/irv.12187. PMC   4186459 . PMID   24734292.
  15. ↑ "BioCryst Files Peramivir NDA for the Treatment of Influenza" (Press release). BioCryst Pharmaceuticals. 2013-12-20.
  16. ↑ "Rapivab: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 11 February 2020.
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