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Azvudine
Azvudine
Azvudine
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Azvudine
Clinical data
Trade names捷倍安, 双新艾克
Other names2′-Deoxy-2′-β-fluoro-4′-azidocytidine (FNC), RO-0622
Legal status
Legal status
  • US: Investigational drug
  • CN: Conditional use Rx
Pharmacokinetic data
Bioavailability83% (rat, dog)[1]
Metabolismliver (CYP3A)[2]
Elimination half-life4 hours (dog)[1]
Identifiers
  • 4-Amino-1-[(2R,3S,4R,5R)-5-azido-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC9H11FN6O4
Molar mass286.223 g·mol−1
3D model (JSmol)
  • C1=CN(C(=O)N=C1N)[C@H]2[C@H]([C@@H]([C@](O2)(CO)N=[N+]=[N-])O)F
  • InChI=1S/C9H11FN6O4/c10-5-6(18)9(3-17,14-15-12)20-7(5)16-2-1-4(11)13-8(16)19/h1-2,5-7,17-18H,3H2,(H2,11,13,19)/t5-,6-,7+,9+/m0/s1
  • Key:KTOLOIKYVCHRJW-XZMZPDFPSA-N

Azvudine is an antiviral drug which acts as a reverse transcriptase inhibitor.[3] It was discovered for the treatment of hepatitis C[4] and has since been investigated for use against other viral diseases such as AIDS and COVID-19,[2][5] for which it was granted conditional approval in China.[6][7]

Azvudine was first discovered in 2007.[8] It costs 350 Chinese yuan per 7 days for COVID, as of November 2022.[9]

Medical uses

[edit]

In July 2021, azvudine became conditionally approved in China for the following indication: "to treat high-viral-load cases of HIV-1, in combination with a nucleoside reverse-transcriptase inhibitor and a non-nucleoside reverse-transcriptase inhibitor". The approval text describes it as a dual reverse transcriptase and Vif inhibitor.[10]

In July 2022, azvudine received emergency conditional approval for COVID-19 in adults.[11] It is believed to work by inhibiting the RNA-dependent RNA polymerase (RdRp) enzyme in the SARS-CoV-2 virus.[12][13]

Adverse effects

[edit]

According to the manufacturer, phase II trials of azvudine in combination with doravirine and tenofovir disoproxil fumarate in HIV patients found an adverse effect profile similar to, but milder, than lamivudine combined with the two drugs. Very common (> 10%) side effects include dizziness, elevated liver enzymes, vomiting, and elevated alkaline phosphatase. Common (> 1%) side effects include nausea, elevated blood lipids, fever, insomnia, tiredness, and diarrhea. Detailed numbers are provided by Genuine in the slides and the medication package insert.[14][15] A boxed warning is present at the beginning of the Chinese package insert, describing a risk of "decrease in absolute neutrophil count, increase in total bilirubin, increase in glutathione aminotransferase, and increase in blood glucose".[15]

The small (n=10) open-label pilot study for azvudine used alone in COVID reported no adverse events.[16]

Non-human models

[edit]

Azvudine is found to be mutagenic in in vitro in the Ames test, CHL test, and in vitro in the mice micronucleus test.[17]

Azvudine is toxic to the reproductive system of rats and rabbit. The minimum reproductive NOAEL found for males is 5.0 mg/kg/d and for females 0.5 mg/kg/d. It is excreted in rat breast milk; the NOAEL for rat pups is 1.5 mg/kg/d.[17]

Azvudine is mainly toxic to the immune system, bone marrow, and digestive system of model animals. The chronic NOAELs are 0.5 mg/kg/d (rat, 3 months), 0.3 mg/kg/d (rat, 26 weeks), and 0.1 mg/kg/d (beagle dog, 1 month and 39 weeks).[17] For comparison, the chronic human dose for HIV treatment is 0.05 mg/kg/d, using the reference 3 mg dose and an average Chinese body mass of 59.5 kg (2014).[citation needed]

History

[edit]

Azvudine was first found in literature in a patent filed by Chang Jun-biao of Zhengzhou University.[8] It received its current name in 2009, when researchers at Roche independently discovered it as a Hep C RNA polymerase inhibitor in vitro.[4] In the following years, Chinese scientists tested it in vitro for a number of targets, most importantly HBV (human and duck) and HTLV-1, two viruses with a reverse transcriptase.[18][19][20]

It was first proposed as an HIV treatment in 2011, when in vitro tests by the Chang group provided positive results.[21] In 2014, its oral pharmokinetics in rats was elucidated.[1] A phase II study (NCT04109183) was finished in March 2019 by Genuine Biotech. In August 2020, the Chang group found that the substance inhibits vif in vitro.[22] In the same month, China's drug regulator (NMPA) decided to fast-track the approval process, labelling it a first-in-class medication.[14] In July 2021, NMPA granted conditional approval for HIV-1.[7] It was included in the 2021 HIV treatment recommendnation by the Chinese Medical Association and Chinese CDC, published October that year.[14] Curiously, no full results of the trial have been made available for this study in any journal detailing the experiment design as of December 2022.[23] Parts of the results are shown on the drug monograph as well as a 2022 slides deck produced by Genuine for the NHSA available on the latter's website.[14]

Azvudine was found to inhibit some coronaviruses in vitro around 2020, leading to an interest in its use in COVID. An open-label pilot study on mild and moderate cases was performed in 2020, with mildly positive results.[16] A phase III trial was performed in 2022 in China. In July 2022, China's drug regulator granted conditional approval for it to be used to treat COVID-19, following a local phase III trial.[6] Initially, no detailed description of the said trial was published in any journals, but state media quoted some numbers from the developer: "40% clinical improvement in 7 days by FNC group, compared to 11% in control".[7] It is unclear how such "improvement" is defined.

Four phase III clinical trials investigated azvudine's efficacy and safety in adults with mild-to-moderate COVID-19. The findings indicate that azvudine may reduce the time to eliminate detectable levels of virus (viral load) and improve symptoms faster than standard treatment. In trials, it was reported to be safe with few side effects. However, some studies produced inconsistent results in terms of symptom improvement and severe illness prevention. Additionally, the studies tended to use a smaller number of participants than other major COVID-19 drug trials.[12][13]

Society and culture

[edit]

Genuine owns two different tradenames for this medication: 双新艾克 (literally "dual new AIDS inhibitor") for HIV use[14] and 捷倍安 (literally "fast extra safe") for COVID use.[7] No generics are available.

Geniune holds one patent related to the drug: the original 2007 patent on the entire class of 2'-fluorine-4'-substituted nucleotides, purchased from Zhengzhou University.[8] Two other Chinese patents on synthesizing the drug are found on Google Patents, but the owners do not appear to be connected to Geniune.[24] Roche held one 2002 patent, CNA028118480A (CN1516590A), over the broader class of 4'-substituted nucleotides. The patent was voided in 2019 after Riboscience, its new holder, stopped paying fees.[25]

References

[edit]

Further reading

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Azvudine

View on Grokipedia
from Grokipedia
Azvudine, chemically known as 1-(4-azido-2-deoxy-2-fluoro-β-D-arabinofuranosyl)cytosine (FNC), is an orally administered nucleoside analog antiviral drug developed in China with broad-spectrum activity against RNA viruses, including SARS-CoV-2, HIV, HCV, EV71, and HBV. It functions as a dual-target inhibitor of viral RNA-dependent RNA polymerase (RdRp), incorporating into viral RNA chains to cause premature termination of replication. Initially derived from the compound RO-9187 and targeted for HIV treatment, azvudine received approval from China's National Medical Products Administration (NMPA) for AIDS therapy on July 21, 2021, and became the first domestically developed oral antiviral for COVID-19 when conditionally approved on July 25, 2022, for adult patients with mild to moderate disease; it remains approved only in China as of 2025. Clinical studies have demonstrated azvudine's efficacy in accelerating clearance, with trials showing a median time to viral negativity of 3.29 days in patients compared to longer durations without treatment, and real-world data from over 11,000 hospitalized patients indicating a 32% reduction in all-cause mortality (HR: 0.68, 95% CI: 0.598–0.775) and a 12% decrease in disease progression risk. It exhibits high oral of approximately 82.7% and a low dosing regimen of 5 mg daily, making it suitable for outpatient use, particularly during the Omicron wave in where it was recommended as a priority treatment. Safety profiles are generally favorable, with mild adverse events such as , , and elevated liver enzymes occurring in 16-20% of patients, and no significant increase in severe (Grade ≥3) reactions compared to controls; however, has been observed in preclinical tests, warranting ongoing monitoring. Beyond antivirals, azvudine shows potential antitumor effects and thymus-homing properties that enhance T-cell immunity, positioning it as a candidate for broader therapeutic applications.

Pharmacology

Mechanism of action

Azvudine, also known as FNC, is a synthetic analog with the 1-(4-azido-2-deoxy-2-fluoro-β-D-arabinofuranosyl). As a derivative, it mimics natural nucleosides and is activated intracellularly through sequential by host kinases to its triphosphate form (FNC-TP). In coronaviruses such as , azvudine inhibits viral replication by targeting the (RdRp). The FNC-TP form competitively binds to the RdRp , incorporates into the growing viral RNA chain in place of , and induces chain termination due to the 2'-fluoro substitution and arabino configuration, which prevent effective further addition despite the presence of a 3'-hydroxyl group. This mechanism results in potent activity, with an EC50 of approximately 0.41 μM against . As a reverse transcriptase inhibitor (NRTI), azvudine exhibits strong activity against retroviruses like -1. After to FNC-TP, it competes with endogenous deoxycytidine triphosphate for incorporation into nascent viral DNA by HIV-1 , leading to chain termination and halting DNA elongation. It demonstrates efficacy against NRTI-resistant HIV strains, with an EC50 of 0.01–0.5 μM and a selectivity index exceeding 1000, indicating minimal to host cells. Azvudine also targets polymerases in (HBV) and (HCV). For HCV, FNC-TP efficiently incorporates into by the viral RdRp (EC50 = 0.024 μM), causing chain termination similar to its action in coronaviruses. Against HBV, it inhibits the viral polymerase with broad-spectrum activity (EC50 ≈ 0.2 μM). Selectivity is achieved through preferential incorporation by viral enzymes over human counterparts; FNC-TP shows poor substrate efficiency for human mitochondrial polymerase (selectivity >5000-fold) but moderate activity against mitochondrial polymerase γ (selectivity ≈120-fold), suggesting potential for limited off-target mitochondrial effects while minimizing overall toxicity. Structurally, azvudine shares analog features with lamivudine, particularly in the base and modified sugar ring, contributing to overlapping NRTI activity but with enhanced potency against lamivudine-resistant strains. Additionally, azvudine modulates immune responses by restoring expression of deaminase (APOBEC3G), which enhances antiviral defense against , and in preclinical COVID-19 models, it reduces pro-inflammatory cytokines such as IL-6 and TNF-α, potentially alleviating through indirect antiviral effects.

Pharmacokinetics

Azvudine is administered orally and is rapidly absorbed, with peak plasma concentrations typically reached within 1-2 hours following a 5 mg dose. The drug demonstrates high oral in preclinical models (82.7% in dogs), supporting once-daily dosing regimens. Following absorption, azvudine is extensively distributed to various tissues, including the lungs, liver, and notably the , where it accumulates preferentially due to selective uptake by T cells, reflecting good tissue penetration, while is low in humans. Metabolism of azvudine occurs primarily intracellularly through sequential by cellular kinases to its active triphosphate form, which inhibits ; hepatic involvement is minimal. The elimination is approximately 10-15 hours, consistent with a mean of 13.8 hours observed in clinical dosing. Excretion is predominantly renal, with the majority of the dose (>70%) recovered unchanged in urine within 12-24 hours in patients, and metabolites also eliminated via this route; less than 10% of unchanged drug may persist beyond initial clearance in some cases. Postprandial administration increases exposure; it is recommended to take on an empty stomach. In special populations, such as those with renal impairment, clearance is reduced, particularly in moderate cases, necessitating dose adjustments to avoid accumulation given the drug's primary renal elimination pathway. Ongoing studies confirm the need for monitoring in patients with decreased glomerular filtration rates.

Medical uses

COVID-19 treatment

Azvudine received conditional approval from China's (NMPA) on July 25, 2022, for the treatment of mild-to-moderate in adults, administered as 5 mg orally once daily for up to 14 days. This approval was based on evidence from phase III clinical trials demonstrating its ability to inhibit replication through (RdRp) inhibition, thereby accelerating viral clearance. In phase III trials, azvudine reduced the time to viral clearance by approximately 2-3 days compared to , with a mean negative conversion time of 3.29 days in treated arms. These trials also showed a lower of progression to severe , including a composite outcome (HR) of 0.08 (95% CI: 0.01–0.62) and an absolute reduction of 0.08 (95% CI: 0.02–0.15). For hospitalized patients, 2024-2025 studies reported reduced mortality, with an HR of 0.14 (95% CI: 0.02–1.13, p=0.07) for all-cause death. Real-world data from 2024-2025 multicenter cohort studies in further supported azvudine's efficacy in hospitalized patients, showing lower all-cause mortality compared to nirmatrelvir-ritonavir (Paxlovid), with HRs of 0.82 (95% CI: 0.676–0.987, p=0.036) in one cohort of 3,606 patients and 0.53 (95% CI: 0.283–0.989, p=0.046) in another of 157 patients. These studies also indicated benefits in reducing hospitalization duration, consistent with phase III findings of shorter stays versus . Additionally, azvudine was associated with fewer adverse effects, such as lower incidences of elevated (ALT) and hypercholesterolemia, compared to Paxlovid. Azvudine has been evaluated in combination therapies, including with standard supportive treatments, showing synergistic antiviral effects that enhance clinical recovery in patients. In cohorts with pre-existing cancer, retrospective analyses observed antitumor effects, such as reduced tumor proliferation and improved immune responses (e.g., increased + and + T cells), alongside symptom alleviation. Despite these benefits, azvudine is not recommended for severe cases as a primary treatment or for patients without specialist oversight, due to contraindications during and , as well as caution in moderate-to-severe liver or dysfunction. Common side effects include transient and , typically resolving within the first 1-2 days of treatment.

HIV/AIDS treatment

Azvudine, a reverse transcriptase inhibitor (NRTI), was conditionally approved by China's on July 21, 2021, for the treatment of HIV-1 infection in adult patients with high viral loads, in combination with other antiretrovirals such as inhibitors and integrase inhibitors when patients are unsuitable for other NRTIs. The approved regimen involves an oral dose of 5 mg once daily. Clinical phase II data demonstrated azvudine's efficacy in reducing and improving immunologic parameters, with CD4+ cell recovery comparable to that achieved with standard NRTIs like lamivudine, albeit at a substantially lower dose requiring only 1% of lamivudine's amount for equivalent antiviral effects. It functions by inhibiting HIV-1 , competing with natural to terminate viral DNA chain elongation. Azvudine is indicated for treatment-naïve patients as well as those with resistance to other NRTIs, attributed to its 4'-azido structural modification, which confers enhanced potency against resistant HIV-1 strains (EC50 values ranging from 0.03 to 6.92 nM ). Gastrointestinal side effects, such as and , may occur with prolonged administration, consistent with other NRTIs. Patients on azvudine-containing regimens require regular monitoring of plasma HIV RNA levels (every 3–6 months once virologically suppressed) and genotypic resistance testing if viral load exceeds 200 copies/mL to assess treatment response and detect potential resistance mutations.

Other indications

Azvudine was originally discovered and developed as a potential treatment for (HCV) infection, where preclinical studies demonstrated its potent inhibition of the viral NS5B (RdRp). As a analog, azvudine's triphosphate form (FNC-TP) acts as a chain terminator, incorporating into nascent viral and halting elongation during replication in models of HCV. These early investigations highlighted its broad activity against positive-strand viruses, including significant reductions in HCV replicon levels without notable in hepatic cell lines. Investigational efforts have also explored azvudine's role in (HBV) treatment, leveraging its inhibition of the viral through a similar reverse transcriptase inhibitor (NRTI) mechanism. In vitro assays confirmed activity against HBV, with azvudine suppressing more effectively than lamivudine against certain drug-resistant strains. Early Phase I clinical data from small cohorts indicated modest reductions in HBV following short-term administration, alongside favorable , though no further progression to approval has occurred due to challenges in achieving sustained . Beyond hepatotropic viruses, azvudine exhibits potential against other RNA viruses owing to its broad-spectrum RdRp inhibition. In vitro studies from 2023 and 2024 demonstrated effective suppression of replication in models of enteroviruses and other positive-strand RNA viruses, with FNC-TP showing nanomolar potency against their polymerases. Preliminary data suggest applicability to , where azvudine disrupted viral RNA synthesis in cell-based assays, though validation remains limited. No specific evidence supports activity against virus, but its mechanism aligns with inhibitors targeting filoviral polymerases. Off-label explorations have investigated azvudine's antitumor effects through immune modulation in preclinical cancer models. In hepatocellular carcinoma xenografts, azvudine inhibited tumor growth by enhancing CD4⁺ and CD8⁺ T-cell infiltration and activation, thereby remodeling the immunosuppressive tumor microenvironment. Similar immunomodulatory benefits were observed in sarcoma and gastric cancer models, where it reduced epithelial-mesenchymal transition and proliferation via regulation of key signaling pathways, without advancing to clinical approval for oncology indications. As of 2025, azvudine lacks regulatory approvals for or other non-HIV/ indications outside , where it remains conditionally authorized primarily for viral infections. Ongoing trials continue to evaluate its utility in exploratory antiviral contexts.

Adverse effects

Clinical adverse effects

In clinical trials and real-world studies of azvudine for treatment, the most frequently reported adverse effects were mild and transient, including elevations in (ALT) and aspartate aminotransferase (AST) levels, gastrointestinal disturbances such as , , and , as well as and . These effects were generally self-limiting and did not lead to significant clinical interventions. Overall incidence in randomized controlled trials was 44.5%, comparable to control groups (49.6%), with serious s occurring in only 0.7-1.2% of patients. In post-marketing and 2024-2025 real-world data from hospitalized patients, discontinuation rates due to s were around 6.6% in some studies, with mixed evidence on tolerability compared to nirmatrelvir-ritonavir (Paxlovid); while discontinuation was higher for azvudine in one study (6.6% vs. 0.97%), it showed lower risks for certain grade 1-3 s such as increased ALT. Rare serious effects included potential hepatic burden in patients with pre-existing or , where azvudine shows a comparable safety profile with potentially lower risks of transient ALT elevations compared to nirmatrelvir-ritonavir, and elevations were reversible upon monitoring. reactions, such as or allergic events, occurred in less than 1% of cases. For long-term use in treatment, phase II trials indicated a favorable safety profile with no severe adverse events, though limited phase III data suggest similar mild effects; are recommended, particularly during extended therapy. Azvudine is not recommended for use in pregnant or lactating women due to preclinical findings. Adverse effect profiles were consistent across COVID-19 and HIV cohorts, with slightly higher gastrointestinal incidence in COVID-19 patients potentially linked to pharmacokinetic factors influencing gut metabolite exposure.

Preclinical findings

Preclinical studies of azvudine (FNC) in animal models, including rodents and non-human primates, demonstrated a generally favorable safety profile, with the risk of carcinogenicity currently under investigation, though genotoxicity was observed in standard assays. In Balb/c mice subjected to acute toxicity testing at doses up to 25 mg/kg, no histopathological changes were noted in major organs such as the liver, kidney, heart, lungs, or spleen, indicating low organ toxicity at therapeutic levels. However, elevated liver enzymes, including aspartate aminotransferase (AST) and alkaline phosphatase (ALP), were observed at higher doses, suggesting potential reversible hepatic effects without structural damage. These findings align with broader rodent studies where azvudine showed no significant genotoxicity in terms of DNA damage or apoptosis markers, supporting its progression to clinical evaluation. Reproductive toxicity assessments in models revealed potential risks, particularly in rats, where azvudine reduced ovarian mass and increased rates, leading to recommendations for caution during (equivalent to FDA Category B). The (NOAEL) was established at 5.0 mg/kg/day for males and 0.5 mg/kg/day for s, with no notable impact on male . These effects were attributed to the drug's analog structure, highlighting the need for selective use in reproductive-age populations. In non-human primate models of , azvudine treatment in SARS-CoV-2-infected rhesus macaques (0.07 mg/kg oral daily for 7 days) significantly reduced viral loads in nasal swabs, blood, lungs, and without causing overt organ damage or histopathological lesions in the lungs or . Mild hematological changes included stable , , , and platelet counts, alongside an increase in percentages (e.g., + and + T cells), indicating immune restoration rather than suppression. No significant adverse effects on overall were reported, underscoring azvudine's tolerability in this model. In vitro evaluations confirmed low cytotoxicity to human cell lines, with a 50% cytotoxic concentration (CC50) exceeding 100 μM against HIV-susceptible cells, yielding a selectivity index greater than 1000 and supporting a wide therapeutic window. Key studies from 2020 to 2022, including the , affirmed no mutagenicity in bacterial reverse mutation assays, though chromosomal aberration tests in lung cells showed positive results, informing risk-benefit assessments for antiviral applications.

History

Discovery and development

Azvudine, chemically known as 2'-deoxy-2'-β-fluoro-4'-azidocytidine (FNC), was developed in the mid-2000s by Chinese researcher Junbiao Chang and his team at , in collaboration with Henan Genuine Biotech Co., Ltd., as a novel analog targeting (HCV) infection. The compound emerged from efforts to create modified cytosine-based s with improved antiviral properties, building on earlier 4'-azido scaffolds like R1479. Initial patent filings for the molecule were submitted by Chang, with the current name assigned in 2009. The key synthesis of azvudine involved structural optimization starting from the HCV NS5B inhibitor RO-9187, incorporating a 2'-β-fluoro substitution to boost anti-HCV potency and a 4'-azido group to enhance metabolic stability and broad-spectrum activity over predecessors such as lamivudine. These modifications replaced the 2'-hydroxyl with in a configuration and added at the 4'-position of the sugar ring, resulting in a compound with superior resistance to enzymatic degradation. The synthesis was first detailed in a 2011 publication by Wang et al., describing the preparation of 2'-deoxy-2'-fluoro-4'-azido nucleosides. Early preclinical work focused on screening against the HCV NS5B , where azvudine demonstrated potent inhibition of viral replication in replicon systems, achieving an IC50 of 24 nM—significantly more effective than lamivudine. Between 2010 and 2015, key studies, including a 2014 report by Wang et al., confirmed its broad activity against HCV alongside and (HBV), with EC50 values as low as 0.018 μM for HCV subgenomic replication, highlighting its chain-terminating mechanism on viral polymerases. From 2016 to 2020, shifted to evaluate azvudine's potential against a wider range of viruses, including HIV-1 through dual inhibition of and accessory protein Vif, as well as emerging pathogens like , driven by its favorable pharmacokinetic profile in preclinical models. This expansion was supported by state-funded initiatives in , including grants from the National Natural Science Foundation of China and the Pingyuan Laboratory, which facilitated iterative optimization and milestones, such as the initial 2012 filing covering its antiviral applications.

Clinical trials and approvals

Azvudine's clinical development began with Phase I trials conducted between 2018 and 2020, primarily focused on assessing and in healthy volunteers. These studies evaluated single doses up to 40 mg and multiple doses up to 10 mg daily for 7 days, demonstrating good tolerability with no significant safety concerns, which supported the selection of a 5 mg once-daily dose for subsequent phases. For HIV treatment, Phase II and III multicenter trials in China enrolled treatment-naive adults from 2020 to 2021, comparing azvudine (5 mg daily) combined with standard regimens against standard therapy alone. These randomized, double-blind studies, involving over 300 participants across multiple sites, met the primary endpoint of non-inferiority in suppression at 48 weeks, with comparable safety profiles. This led to conditional approval by China's (NMPA) in July 2021 for HIV-1 infection in adults. In response to the , Phase III trials for azvudine were initiated in 2021 and completed by 2022, including a key multicenter, randomized, double-blind, -controlled study in with over 1,200 adults with mild-to-moderate . The trials used a 5 mg daily dose for up to 7 days and achieved the primary endpoint of accelerated viral clearance, reducing time to negativity by approximately 3 days compared to , alongside symptom improvement. Four such Phase III studies across , , and supported conditional NMPA approval in July 2022 for treating pneumonia in adults. Post-2022, real-world studies from 2024 to 2025, including large retrospective cohorts in involving thousands of hospitalized patients, confirmed azvudine's effectiveness, with adjusted hazard ratios for all-cause mortality around 0.68-0.69 versus non-users, indicating reduced risk without increased adverse events. International expansion included Phase III trials in beyond , such as in , evaluating efficacy in diverse populations, though no approvals have been granted by the U.S. FDA as of November 2025.

Society and culture

Regulatory status

Azvudine (FNC) received conditional approval from China's (NMPA) in July 2021 for the treatment of HIV-1 infection in adults. In July 2022, the NMPA granted conditional marketing authorization for azvudine as an oral antiviral for adults with mild to moderate , making it the first domestically developed oral anti-COVID-19 drug in .00117-5) As of April 2025, this approval remains conditional, with ongoing requirements for confirmatory Phase IV studies to support full marketing authorization. In 2025, the NMPA accepted a Phase II application for azvudine monotherapy in hematological tumors and approved an application for its combination with dosimertinib in non-small cell . Outside China, azvudine has not received regulatory approval from major authorities such as the U.S. (FDA) or the (EMA), due to insufficient data meeting international standards for efficacy and safety. No emergency use authorizations or approvals have been reported in other Asian countries as of November 2025. The approved indications for azvudine are restricted to adults aged 18 years and older. It is contraindicated in patients with severe renal impairment (estimated <30 mL/min) and requires dose adjustment (to 3 mg/day) for moderate renal impairment (eGFR 30–60 mL/min); similarly, caution or dose adjustment is advised for moderate to severe hepatic impairment due to potential risks of toxicity.00158-X/fulltext) Real-world studies through 2025 have not prompted post-approval label expansions, though they continue to inform safety monitoring. Azvudine is not included on the World Health Organization's List of for COVID-19.

Availability and access

Azvudine is primarily manufactured by Genuine Biotech in , with production facilities designed specifically for the drug and its candidates, covering the full cycle from synthesis to packaging. The company has partnered with entities like for commercialization and distribution support, enabling broader market reach. Following the peak of the , Genuine Biotech expanded its supply chain, achieving an annual production capacity of approximately 3 billion tablets by 2025 to meet domestic demand. As of November 2025, Genuine Biotech filed for an on the to fund further development. In , Azvudine is marketed under the brand name Jiebeian, developed by Genuine Biotech, with the chemical code FNC commonly referenced in . Local firms, including Double-Crane Pharmaceutical, Xinhua Pharmaceutical, and others, have begun contributing to production as of 2024, supporting generic-like under licensed agreements to increase supply. This has facilitated wider , with the stocked in pharmacies nationwide since late 2022 and included in the national reimbursement drug list for renewed access in 2024. Pricing in has been adjusted to enhance affordability, starting at 270 yuan (about $40) for a bottle of 35 one-milligram tablets upon launch in , and reduced by 2023 for inclusion in medical insurance programs. This equates to roughly 811 yuan (approximately $115) for a 14-day course at the standard dose of five 1-mg tablets daily, though costs can vary by region and remain higher in markets—estimated at $50-100 per course—due to protections and limited international licensing. Exports remain restricted, with stockpiling prioritized for preparedness in rather than global distribution. Access challenges persist in low-income countries outside , where high import costs and lack of regulatory approvals limit availability, exacerbating inequities in antiviral treatment for and potential use. As of 2025, initiatives for generic licensing have emerged in and through partnerships with local manufacturers, aiming to reduce prices and improve equity, though implementation remains in early stages. The drug's market entry was enabled by Chinese approvals for in 2021 and conditional use in programs from 2022 onward.

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