Drugs, Health Technologies, Health Systems
Key Messages
What Is the Issue?
There is a need to identify drugs currently in development (pipeline drugs) intended to prevent or treat influenza.
Specifically, policy-makers would like to identify those drugs that have ongoing or recently completed phase II or phase III randomized controlled trials (RCTs) and are not yet approved for use by Health Canada for influenza.
What Did We Do?
An information specialist did a tailored literature search across major databases to identify relevant RCTs on antiviral drugs for influenza, focusing on information published in English since January 1, 2020, and completed on November 8, 2024.
What Did We Find?
We identified a total of 17 emerging drugs in 26 completed or ongoing RCTs, mainly testing treatments for adults with uncomplicated influenza, with some studies including children and adolescents.
The evidence included 2 prevention studies and 3 challenge studies for influenza.
Most drugs were compared to a placebo and the number of participants in these trials ranged from 46 to 5,000.
What Does It Mean?
There are promising new drugs in development for treating adults with uncomplicated influenza.
This report provides information on pipeline drugs intended to prevent or treat influenza. Specifically, it identifies drugs that have completed phase II or phase III RCTs and are not approved for use by Health Canada for influenza. In addition, it identifies drugs that have ongoing phase II or phase III RCTs. It is important to note that this report is not a systematic review and does not describe results nor does it include a critical appraisal of the identified studies. This document is not intended to provide recommendations or advice.
To identify and describe the study and population characteristics of ongoing or recently completed phase II or phase III RCTs that evaluate drugs to prevent or treat influenza and are not currently approved by Health Canada for this indication.
What antiviral drugs are in the pipeline for influenza A or B?
An information specialist conducted a literature search on key resources including MEDLINE, Embase, the Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and Health Canada’s Clinical Trials Database. The search approach was customized to retrieve a limited set of results, balancing comprehensiveness with relevance. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. Search concepts were developed based on the elements of the research question and selection criteria. The main search concepts were antivirals or other anti-influenza drugs and influenza. Search filters were applied to limit retrieval to RCTs or controlled clinical trials. Retrieval was limited to the human population. For the Embase search, retrieval was also limited to conference abstracts. The search was completed on November 8, 2024, and limited to English-language documents published since January 1, 2020.
The studies of drugs to prevent or treat influenza were selected based on the inclusion and exclusion criteria shown in Table 1 and if the drugs of interest were antiviral drugs or drugs with antiviral-like properties.
Several articles obtained through the grey literature search were reviewed to identify new molecules.1-6
Source of information | Inclusion criteria | Exclusion criteria |
|---|---|---|
MEDLINE | Phase II and phase III RCTs | Studies of drugs that have already been approved in Canada to treat or prevent influenza Studies of drugs that are already approved for other indications in Canada and potentially repurposed for influenza in the future Studies of vaccines, devices, traditional herbs or medicines, natural health products, and dietary supplements Dose finding studies or pharmacokinetics or pharmacodynamics studies Drugs that are no longer in development according to the manufacturer’s website information or other |
Embase | Conference abstracts of phase II and phase III RCTs | |
ClinicalTrials.gov | Phase II and phase III interventional studies that are completed, active, recruiting, or not yet recruiting Estimated primary completion date after January 1, 2020 | The exclusion criteria previously mentioned Studies that are withdrawn, suspended, terminated, or with unknown status Studies terminated early due to futility |
RCTs = randomized controlled trials.
A total of 17 drugs (Table 2) with 26 RCTs, completed or ongoing, were identified. Of these, 5 drugs are marketed in 1 or more countries. Many RCTs were treatment studies and included adults with uncomplicated influenza. One treatment study included children aged 2 to 11 years and 1 treatment study included children aged 6 months to 2 years. Five studies included adolescents aged 12 to 17 years.
There were 2 prevention studies and 3 challenge studies for influenza. In 1 challenge study, the 2009 pandemic strain of influenza A (influenza A/California/07/2009 H1N1) was used to inoculate healthy volunteers.7
The emerging drugs were compared to an active control in 5 studies and the remainder were compared to placebo. The study sample size ranged from 46 to 5,000 participants.
The characteristics of the RCTs are captured in Appendix 1.
Table 2: Drugs in the Clinical Pipeline
Drug | Manufacturer | Drug type |
|---|---|---|
CC42344 | Antiviral (PB2 inhibitor) | |
CD388 | Antiviral (neuraminidase inhibitor) | |
Deunoxavir marboxil (ADC189) | Antiviral (PA inhibitor) | |
Enisamium (FAV00A; Amizon)a | Antiviral (RNA synthesis inhibitor) | |
Favipiravir (T-705; Avigan)b | Antiviral (PB1 inhibitor) | |
GP681 | Antiviral (PA inhibitor) | |
Ingavirinc,d | Antiviral (NP inhibitor) | |
MHAA4549A | Genentech, Inc. | Monoclonal antibody |
Neumifil (HEX17) | Antiviral (carbohydrate binding module) | |
Norketotifen | Antihistamine (metabolite of ketotifen) | |
Nitazoxanide (Alinia)e | Antiprotozoal | |
Onradivir (ZSP1273) | Antiviral (PB2 inhibitor) | |
Raphamin (MMH-407)c | Antiviral (MHC inhibitor) | |
Seloxavir marboxil (ZX-7101A) | Antiviral (PA inhibitor) | |
Umifenovir (DB13609; Arbidol)c,f | Antiviral (HA-induced membrane fusion inhibitor) | |
VIS410 | Monoclonal antibody | |
XC221 | MOA undefined |
HA = hemagglutinin; MHC = major histocompatibility complex; MOA = mechanism of action; NP = nucleoproteins; PA = polymerase acidic protein; PB1 = polymerase basic protein 1; PB2 = polymerase basic protein 2; RNA = ribonucleic acid.
aAvailable in 11 countries in eastern Europe.
bAvailable in Japan.
cAvailable in Russia.
dAlso known as pentanedioic acid imidazolyl ethanamide; IEPA; ingamine; pentanoic acid; or vitaglutam.
eAvailable in the US.
fAvailable in China.
A search was conducted to identify phase II and phase III RCTs that evaluated emerging drugs to prevent or treat influenza. A total of 26 RCTs were retrieved which included 17 emerging drugs.
The pipeline for drugs to treat adults with uncomplicated influenza is promising. There is a limited number of studies specific to the prevention of influenza, the treatment of severe influenza, and in children aged 17 years and younger.
Interpretation of the findings of the bulletin must take into consideration the following limitations:
The search for RCTs was not systematic. The list may be incomplete and missing studies of drugs that would fulfill the inclusion criteria.
The status of the identified drugs may have changed since the completion of the literature searches. Some drugs may no longer be in development.
The published or posted results were not reviewed to determine if they were favourable to the identified drugs; hence, the list may include RCTs with negative findings.
1.Coughlan L, Neuzil KM. Outpacing antiviral resistance: new treatments for influenza virus infection. Lancet Infect Dis. 2024;24(5):447-449. PubMed
2.Kumari R, Sharma SD, Kumar A, et al. Antiviral Approaches against Influenza Virus. Clin Microbiol Rev. 2023;36(1):e0004022. PubMed
3.Li Y, Huo S, Yin Z, et al. Retracted and republished from: “The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs”. mBio. 2024;15(5):e00175-00124. PubMed
4.Liu C, Hu L, Dong G, et al. Emerging drug design strategies in anti-influenza drug discovery. Acta Pharm Sin B. 2023;13(12):4715-4732. PubMed
5.Malik S, Asghar M, Waheed Y. Outlining recent updates on influenza therapeutics and vaccines: A comprehensive review. Vaccine X. 2024;17:100452. PubMed
6.Meseko C, Sanicas M, Asha K, Sulaiman L, Kumar B. Antiviral options and therapeutics against influenza: history, latest developments and future prospects. Front Cell Infect Microbiol. 2023;13:1269344. PubMed
7.Sloan SE, Szretter KJ, Sundaresh B, et al. Clinical and virological responses to a broad-spectrum human monoclonal antibody in an influenza virus challenge study. Antiviral Res. 2020;184:104763. PubMed
Please note that this appendix has not been copy-edited.
Table 3: Ongoing Randomized Controlled Trials (Active, Recruiting, or Not Yet Recruiting)
Intervention(s) | Comparator(s) | Study Design, Location(s), and Sample Size | Study Population | Estimated Primary Completion Date | ClinicalTrials.gov Reference |
|---|---|---|---|---|---|
Phase II | |||||
CC42344 | Placebo | Single centre, double-blind UK N = 96 | Adults (18 to 55 years) – challenge study for influenza A | June 2024 | |
CD388 | Placebo | Multicentre (57 sites), double-blind US, UK N = 5,000 | Adults (18 to 63 years) not at risk for influenza complications – prevention study | September 2025 | |
Favipiravir (T070; Avigan) and other antiviral drugs (includes laninamivir) | No treatment and against each other | Multicentre (4 sites), open-label, adaptive, platform trial 4 countries N = 3,000 | Adults (18 to 60 years) with early symptomatic uncomplicated influenza A or B | 01 January 2027 | |
Phase III | |||||
Deunoxavir marboxil (ADC189) | Baloxavir marboxil | Multicentre, double-blind China N = 165 | Children (2 to 11 years) with influenza A or B | 31 December 2024 | |
GP681 | Placebo | Multicentre, double-blind Location NR N = 328 | Adults and adolescents (12 and older) with influenza at high risk of influenza complications | 30 December 2025 | |
GP681 | Placebo | Multicentre, double-blind Location NR N = 748 | Adults and adolescents (12 years and older) for post-exposure prophylaxis against influenza | 30 July 2027 | |
Seloxavir marboxil (ZX-7101A) | Placebo | Multicentre, double-blind China N = 360 | Adolescents (12 −17 years) with uncomplicated influenza | 30 November 2024 | |
NR = not reported.
Table 4: Completed Randomized Controlled Trials With Published or Posted Results
Intervention(s) | Comparator(s) | Study Design, Location(s), and Sample Size | Study Population | Key Outcome | ClinicalTrials.gov or PubMed Reference |
|---|---|---|---|---|---|
Phase II | |||||
MHAA4549A combined with oseltamivir | Placebo combined with oseltamivir | Multicentre (68 sites), double-blind 18 countries N = 166 | Adult inpatients (18 to 95 years) with severe influenza A infection | Time to normalization of respiratory function | |
Neumifil (HEX17) | Placebo | Single centre, double-blind UK N = 104 | Adults (18 to 55 years) – challenge study for influenza | Incidence of symptomatic influenza | |
Onradivir (ZSP1273) | Placebo | Multicentre (20 sites), double-blind China N = 205 | Adult outpatients (18 to 65 years) with acute uncomplicated influenza A | Time to alleviate influenza symptoms | |
VIS410 | Placebo | Single centre, double-blinded Belgium N = 46 | Adults (18 to 45 years) – challenge study for influenza (used a 2009 pandemic strain of influenza A) | Viral load | |
Phase III | |||||
Favipiravir (T-905; Avigan) | Placebo | Multicentre, double-blind 14 countries N = 855 | Adults (18 to 80 years) with acute influenza-like illness | Time to alleviation of symptoms and resolution of fever | |
Nitazoxanide (Alinia) | Placebo | Multicentre (38 sites), double-blind 3 countries N = 1,030 | Adults and adolescents (12 years and older) with uncomplicated influenza A or B | Time from first dose to symptom response | |
Nitazoxanide (Alinia) combined with Oseltamivir | Oseltamivir | Single centre, blinded India N = 67 | Adult inpatients (age range NR) with seasonal influenza | Time for resolution of fever | |
Raphamin (MMH-407) | Placebo | Multicentre (26 sites), double-blind Russia N = 240 | Adult outpatients (18 to 70 years) with acute respiratory viral infection | Time to resolution of symptoms | |
Umifenovir (DB13609; Arbidol) | Oseltamivir | Multicenter (14 sites), open label China N = 412 | Adult outpatients (18 years and older) with suspected influenza | Time to normal body temperature | |
Phase II and III | |||||
Seloxavir marboxil (ZX-7101A) | Placebo | Single centre, double-blind, adaptive design China N = 900 | Adults (18 to 64 years) with uncomplicated influenza | Time to alleviation of influenza symptoms | |
Phase Unknown | |||||
Enisamium iodide (FAV00A; Amizon) | Placebo | Single centre, blinding NR Russia N = 124 | Adult outpatients (aged 18 to 55 years) with influenza and influenza-like illness without risk factors for severe disease | Duration of disease | |
NR = not reported.
Table 5: Completed Randomized Controlled Trials Without Results
Intervention | Comparator | Study Design, Sample Size, and Location(s) | Study Population | Key Outcome | ClinicalTrials.gov |
|---|---|---|---|---|---|
Phase II | |||||
GP681 | Placebo | Single centre, double-blind China N = 216 | Adults (18 to 65 years) with uncomplicated acute influenza | Time to alleviation of influenza symptoms | |
Norketotifen | Placebo | Multicentre (20 sites), double-blind US N = 315 | Adult outpatients (18 to 64 years) with uncomplicated acute influenza | Time to alleviation of the symptoms of influenza-like illness | |
Norketotifen | Placebo | Multicentre (18 sites), double-blind US N = 238 | Adult outpatients (18 to 64 years) with uncomplicated acute influenza | Time to alleviation of the symptoms of influenza-like illness | |
XC221 | Placebo | Multicentre (9 sites), double-blind Russia N = 255 | Adults (18 to 65 years) with uncomplicated influenza or other acute viral upper respiratory infections | Time to resolution of all symptoms | |
Phase III | |||||
GP681 | Placebo | Single centre, double-blind China N = 591 | Adults and adolescents (12 to 65 years) with uncomplicated acute influenza | Time to alleviation of influenza symptoms | |
Ingavirin | Placebo | Multicentre (8 sites), double-blind Russia N = 240 | Outpatient children (6 months-2 years) with influenza and other acute respiratory viral infections | Time to resolution of symptoms | |
Onradivir (ZSP1273) | Placebo | Multicentre (76 sites), double-blind China N = 591 | Adult outpatients (18 to 64 years) with acute uncomplicated influenza A | Time to alleviation of symptoms | |
XC221 | Placebo | Multicentre (13 sites), double-blind Russia N = 260 | Adult outpatients (18 to 65 years) with uncomplicated influenza or other acute respiratory viral infections | Time to resolution of all symptoms | |
ISSN: 2563-6596
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