Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate: A study of the 2017/18 and 2018/19 seasons and comparison with the 2011/12 to 2016/17 Japanese influenza seasons.

INTRODUCTION: Large scale investigation of the clinical effectiveness of neuraminidase inhibitors for circulating influenza viruses are important along with the surveillance of virus susceptibility in vitro. METHODS: The duration of fever and other influenza symptoms as markers of the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) were investigated in the Japanese 2017/18 and 2018/19 influenza seasons and compared with the results of the previous six seasons. RESULTS: Influenza A(H1N1)pdm09, A(H3N2), and B were found in 14, 45, and 52 patients in the 2017/18 season and in 22, 62, and 0 in the 2018/19 season, respectively. The median duration of fever for B was significantly longer than for A(H1N1)pdm09 and A(H3N2) in the 2017/18 season (p = 0.0461) and for A(H3N2) than for A(H1N1)pdm09 in the 2018/19 season (p = 0.0290). However, the differences were subtle in both seasons for other symptoms, with no significant differences in their median duration in comparison of the circulating types/subtypes. Over the eight seasons with the previous six seasons added, the median durations of fever were consistently longer for B than for A, but the relation between the A subtypes was inconsistent. The median durations of fever were comparable over the eight seasons for the virus types/subtypes, as were the median durations of other symptoms. The percentage of febrile patients decreased in a similar pattern over the eight seasons for each type/subtype. CONCLUSIONS: The results confirmed that laninamivir has continued to be clinically effective against all types/subtypes of influenza viruses, with no safety issues.

Susceptibility of epidemic viruses to neuraminidase inhibitors and treatment-emergent resistance in the Japanese 2019-20 influenza season.

OBJECTIVES: To investigate the susceptibility of epidemic influenza viruses to neuraminidase inhibitors (NAIs) and the emergence of resistant viruses after treatment, a prospective, observational study was done in the 2019-20 Japanese influenza season. METHODS: Influenza viruses were isolated before and twice after treatment, the first at day 5 and the second at day 10. The 50% inhibitory concentrations (IC50s) to oseltamivir, zanamivir, peramivir, and laninamivir were measured and compared with those of 2010-11 to 2018-19 seasons. NA amino acid sequences were analyzed by next generation sequencing (NGS). RESULTS: The IC50 geometric means of the NAIs for 128 A(H1N1)pdm09, 2 A(H3N2), and 33 B were comparable to those of the previous seasons. Only 2 (1.6%) A(H1N1)pdm09 with significantly high IC50 to oseltamivir were found pretreatment. No A(H3N2) or B had resistance. Treatment-emergent oseltamivir resistance was found in 2 among 33 oseltamivir-treated A(H1N1)pdm09, only at the second follow-up. The NGS indicated a rapid increase in the proportion of H275Y to wild type, from 0% to almost 100% between days 5 and 10. CONCLUSIONS: These results suggest the continued effectiveness of these NAIs for epidemic influenza in Japan. Treatment-emergent resistant H275Y A(H1N1)pdm09 viruses were detected after oseltamivir treatment, rapidly replacing the wild type.

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2018-19 season: Comparison with the 2010-11 to 2017-18 seasons.

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) of the epidemic viruses in the 2018-19 Japanese influenza season, we measured the 50% inhibitory concentration (IC50) of four NAIs, oseltamivir, zanamivir, peramivir, and laninamivir, for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2017-18 seasons. Viral isolation was done with specimens obtained prior to and after treatment, and the type/subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Virus isolates, 51 A(H1N1)pdm09, 125 A(H3N2), and one B, were measured in the 2018-19 season and the geometric mean IC50s of the four NAIs were quite comparable to the previous eight studied seasons. No A(H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2018-19 season prior to drug administration, although such A(H1N1)pdm09 were found in two, two, and two samples in the 2010-11, 2013-14, and 2015-16 seasons, respectively. No isolates with highly reduced sensitivity to the four NAIs were found for A(H3N2) or B through the 2010-11 to 2018-19 seasons. Among 18 samples with A(H1N1)pdm09 virus isolated after NAI administration, highly reduced sensitivity to oseltamivir and peramivir was detected from one of the five patients treated with oseltamivir. These results suggest that the sensitivity to the four commonly used NAIs has been maintained, although viruses with highly reduced sensitivity to oseltamivir and peramivir have emerged in some adult patients treated with oseltamivir.

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2017-18 season: Comparison with the 2010-11 to 2016-17 seasons.

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) of the viruses epidemic in the 2017-18 Japanese influenza season, we measured the 50% inhibitory concentration (IC50) for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2016-17 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 237 virus isolates, 50 A(H1N1)pdm09, 92 A(H3N2), and 95 B were measured. No A(H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2017-18 season. No isolates with highly reduced sensitivity to the four NAIs have been found for A(H3N2) or B from the 2010-11 to 2017-18 seasons. The geometric mean IC50s of the four NAIs were quite consistent during the eight studied seasons. These results indicate that the sensitivity to the four commonly used NAIs has been maintained.

Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons.

The duration of fever and symptoms after laninamivir octanoate hydrate (laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2016-17 season: Comparison with the 2010-11 to 2015-16 seasons.

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2016-17 Japanese influenza season, we measured the 50% inhibitory concentration (IC50) of these NAIs for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2015-16 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 276 virus isolates, 6 A (H1N1)pdm09 (2.2%), 249 A (H3N2) (90.2%), and 21 B (7.6%), had the IC50 measured for the four NAIs. B isolates included 11 (52.4%), 9 (42.9%), and one (4.8%) of the Victoria, Yamagata, and undetermined strains, respectively. No A (H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2016-17 season. No isolate with highly reduced sensitivity to the four NAIs have been found for A (H3N2) or B from the 2010-11 to 2016-17 seasons. No significant trend of increase or decrease was found in the geometric mean IC50s of the four NAIs during the seven studied seasons. These results indicate that the sensitivity to the four commonly used NAIs has been maintained and that any change in the effectiveness of these NAIs would be minute. Common usage of NAIs for patient treatment has not been a driving force in the selection of NAI resistant viruses.

Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate; comparison of the 2011/12 to 2015/16 Japanese influenza seasons.

The duration of fever and symptoms after laninamivir octanoate hydrate (laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2015-16 season: Comparison with the 2010-11 to 2014-15 seasons.

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2015-2016 influenza season in Japan, we measured the 50% inhibitory concentration (IC50) of NAIs for influenza virus isolates and compared them with the results from the 2010-11 to 2014-15 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Influenza viruses were isolated: 210 influenza A(H1N1)pdm09 (67.3%), 20 A(H3N2) (6.4%), and 82 B (26.3%), and for the Victoria and Yamagata lineages the numbers were 53 (64.6%) and 28 (34.1%), respectively, with one unknown. Two A(H1N1)pdm09 isolates showed a high IC50 for oseltamivir (130 and 150 nM). No isolate showed a very high IC50 for A(H3N2) or B. The ratios of geometric mean IC50 of the 2015-2016 influenza season to those of the 2010-2011 to 2014-2015 influenza seasons ranged from 0.62 to 1.78 for A(H1N1) pdm09. The range was 0.73-1.35 for A(H3N2) and 0.48-1.12 for B. No significant trend of increase or decrease in IC50 was found for any of the four NAIs. Although some isolates showed highly reduced sensitivity to oseltamivir among the A(H1N1)pdm09 isolates, the currently epidemic influenza A(H1N1)pdm09, A(H3N2), and B viruses are susceptible to all four NAIs, with no trend toward decreased sensitivity.

Duration of fever and other symptoms after the inhalation of laninamivir octanoate hydrate for influenza treatment; comparison among the four Japanese influenza seasons from 2011-2012 to 2014-2015.

The duration of fever and other symptoms as markers of the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) were investigated in the Japanese 2014-2015 influenza season and the results were compared with those of the previous three seasons, 2011-2012 to 2013-2014. From these four seasons, the data of 636 influenza A(H3N2) and 128 influenza B patients was available for analysis. No significant difference was found in their baseline characteristics. The median duration of fever for all A(H3N2) patients ranged from 32.0 to 41.0 h. The duration of fever in the 2014-2015 season was significantly shorter than that in the 2012-2013 and 2013-2014 seasons (p = 0.0204 and 0.0391, respectively), but the differences were within nine hours. The median duration of symptoms for A(H3N2) ranged from 80.0 to 89.0 h, with no significant difference among the four seasons (p = 0.2222). The median duration of fever for B patients ranged from 43.0 to 50.0 h, with no significant difference among the four seasons. The duration of the symptoms for B varied by season, but no significant difference was found among the four seasons. Over the four seasons, 44 adverse events were reported from among 921 patients, with all resolving without treatment. These results indicate the continuing effectiveness of laninamivir against influenza A(H3N2) and B, with no safety issues. It is unlikely that the clinical use of laninamivir has caused viral resistance in the currently epidemic viruses.

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 Japanese influenza seasons.

To assess the extent of viral resistance to the four neuraminidase inhibitors (NAIs), we measured their 50% inhibitory concentration (IC50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. IC50 was measured for 200 influenza A(H3N2) and 19 influenza B in the 2014-2015 season, and no virus with highly reduced sensitivity to the four NAIs was detected. The ratios of the geometric means of the A(H3N2) IC50s of 2014-2015 to those of the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 seasons ranged from 0.72 to 1.05, 0.82 to 1.22, 0.69 to 1.00, and 0.70 to 1.03, respectively. The ratios of the geometric mean of the B IC50s to the previous four seasons ranged from 0.59 to 1.28, 0.66 to 1.34, 0.84 to 1.21, and 1.06 to 1.47, respectively. There was no trend in the change of the IC50s for A(H3N2) or B. Significant differences were found in some seasons, but the differences in the IC50s were all less than two fold. These results show change in the geometric mean IC50 by season but with no trend, which indicates that the influence of viral mutation on the effectiveness of these NAIs was minute for A(H3N2) and B over the past five seasons.

Long-acting Neuraminidase Inhibitor Laninamivir Octanoate as Post-exposure Prophylaxis for Influenza.

BACKGROUND: A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, has been proven to be effective in the treatment of influenza but not for post-exposure prophylaxis. METHODS: We conducted a double-blind, multicenter, randomized, placebo-controlled study to determine if a single administration of laninamivir octanoate 40 mg was superior to placebo for post-exposure prophylaxis. Eligible participants who had cohabited with an influenza patient within 48 hours of symptom onset were randomly assigned (1:1:1) to 1 of 3 groups: 40 mg of laninamivir octanoate single administration (LO-40SD), 20 mg of laninamivir octanoate once daily for 2 days (LO-20TD), or placebo. The primary efficacy endpoint was the proportion of participants who developed clinical influenza (defined as influenza virus positive, an axillary temperature >37.5°C, and at least 2 symptoms) over a 10-day period. RESULTS: A total of 803 participants were enrolled, with 801 included in the primary analysis. The proportions of participants with clinical influenza were 4.5% (12/267), 4.5% (13/269), and 12.1% (32/265) in the LO-40SD, LO-20TD, and placebo groups, respectively. A single administration of laninamivir octanoate 40 mg significantly reduced the development of influenza compared with placebo (P = .001). The relative risk reductions compared with the placebo group were 62.8% and 63.1% for the LO-40SD and LO-20TD groups, respectively. The incidence of adverse events in the LO-40SD group was similar to that of the LO-20TD and placebo groups. CONCLUSIONS: A single administration of laninamivir octanoate was effective and well tolerated as post-exposure prophylaxis to prevent the development of influenza. CLINICAL TRIALS REGISTRATION: JapicCTI-142679.

Clinical outcome of laninamivir octanoate hydrate for influenza in the 2013-2014 Japanese season.

The clinical outcome of laninamivir octanoate hydrate (laninamivir) in the Japanese 2013-2014 influenza season was investigated. A total of 235 patients were enrolled, of whom 222 were evaluated for the duration of fever and other symptoms. The types/subtypes were 101 A(H1N1)pdm09 (45.5%), 37 A(H3N2) (16.7%), and 84 B (37.8%). The median durations of fever were 32.0, 41.0, and 50.0 h, and the median durations of symptoms were 74.5, 85.0, and 95.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively. The differences among the three groups were not statistically significant. There was no significant difference in the duration of fever or symptoms between patients under 10 and 10 years or over. The median durations of fever were 46.0 and 58.0 h and the median durations of symptoms were 95.0 and 77.0 h for the Yamagata and Victoria lineages, respectively. The virus positive rates at day 5 were significantly different at 31.5% (28/89), 12.1% (4/33), and 34.7% (26/75) for the three type/subtypes, respectively. The virus positive rates for A(H1N1)pdm09 and B were significantly higher for the patients under 10 years than for the patients 10 years or older. (p = 0.0379 and 0.0320, respectively). No significant increase was found between the IC(50) of days 1 and 5. No adverse drug reactions associated with laninamivir were reported. These results indicate the continuing clinical utility of laninamivir against influenza, irrespective of the virus type/subtype or lineage, and that it is unlikely that the clinical use of laninamivir will lead to selection of resistant virus.

In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against clinical isolates of influenza virus in the Japanese 2012-2013 season.

The neuraminidase inhibitors (NAIs) oseltamivir phosphate (Tamiflu(®)), zanamivir (Relenza(®)), laninamivir octanoate (Inavir(®)), and peramivir (Rapiacta(®)) have been available for the treatment of influenza in Japan since 2010. The emergence of resistant virus to any of the NAIs is a great concern for influenza treatment. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC50) of each NAI for influenza virus isolates in the 2012-2013 influenza season and compared the results to those of the 2010-2011 and 2011-2012 influenza seasons. Viral isolation of specimens obtained prior to treatment was done using Madine-Darby canine kidney cells, and the type and subtype of influenza, A(H1N1)pdm09, A(H3N2), or influenza B, was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 329 influenza viruses were isolated:5 influenza A(H1N1)pdm09 (1.5%), 316 influenza A(H3N2) (96.1%), and 8 influenza B (2.4%). No isolate showed an IC50 value exceeding 50 nM for any of the neuraminidase inhibitors. The IC50 values for A(H3N2) and B were similar to those of the 2010-2011 and 2011-2012 seasons. No isolate showed an increased IC50 value for A(H1N1)pdm09. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC50 values to increase at present.

Continued effectiveness of laninamivir octanate hydrate for influenza treatment in Japan: comparison between the 2011-2012 and 2012-2013 influenza seasons.

The clinical effectiveness of Laninamivir octanoate hydrate (laninamivir) was investigated in the Japanese 2012-2013 influenza season for comparison with that of the Japanese 2011-2012 influenza season. A total of 235 patients were enrolled, of whom 210 were evaluated for the duration of fever and other symptoms. The median durations of fever for A(H3N2) were 32.0 and 38.0 h and the median durations of symptoms for the A(H3N2) were 102.0 and 84.0 h for patients aged under 10 and 10 years or older, respectively. All four influenza B patients were 10 years or older, and their median duration of fever was 43.0 h and the median duration of symptoms was 71.0 h. There was no significant difference in the duration of fever or symptoms between the two seasons. The rates of patients A(H3N2) virus positive at day 5 were 37.2% (16/43) and 12.8% (18/141) for those aged under 10 years and 10 years or older, respectively. The virus positive rate was significantly higher for the patients under 10 years than for the patients aged 10 years or older (p < 0.0001). No significant change in IC50 value was found between days 1 and 5. Adverse drug reactions were reported by 2 of the 231 patients (0.87%), but neither was serious. These results suggest that laninamivir continued to be effective against influenza A(H3N2) with no safety issues and that it is unlikely that the clinical use of laninamivir will lead to virus resistance.

The duration of fever and other symptoms after the initiation of laninamivir octanoate hydrate in the Japanese 2011-2012 influenza season.

Laninamivir octanoate hydrate (laninamivir) is a long-acting, single inhalation neuraminidase inhibitor that was approved in Japan in 2010 for the treatment of influenza A and B virus infection. We investigated the duration of fever and other symptoms after the initiation of laninamivir in the Japanese 2011-2012 influenza season. Virus isolation was done and the 50% inhibitory concentration (IC50) was measured for the virus isolates at days 1 and 5. For 211 patients (A(H3N2): 190, B: 21), the median durations of fever of A(H3N2) and B patients were 33.0 and 50.0 h, respectively (p = 0.0989). Fever was resolved within 72 h after inhalation by 89.7% of the A(H3N2) patients and by 81.0% of the patients with B. The median durations of symptoms for A(H3N2) and B patients were 89.0 and 94.0 h, respectively (p = 0.5809). On day 5, the influenza virus-positive rates for A(H3N2) and B patients were significantly different: 25.8% (40/155) and 70.6% (12/17), respectively (p < 0.0001). No significant change in IC50 value was found between day 1 and day 5 for any of the four tested neuraminidase inhibitors, and no IC50 value exceeded 50 nM. The incidence of adverse drug reactions was 1.3% (3/234), with no serious reactions reported. These results show that laninamivir was effective for the treatment of both influenza A(H3N2) and B in this study, with no safety issues. The clinical effectiveness of laninamivir for A(H3N2) was superior to that for B.

In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in Japan.

The neuraminidase inhibitors oseltamivir phosphate (Tamiflu®), zanamivir (Relenza®), laninamivir octanoate (Inavir®), and peramivir (Rapiacta®) have been available for the treatment of influenza in Japan since 2010. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC50) of each drug for influenza virus isolates from the 2011-2012 influenza season. Specimens were obtained from patients prior to treatment. Viral isolation was done using Madine-Darby canine kidney cells, and the type and subtype of influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. The lineage of influenza B virus was determined by direct sequencing of the hemagglutinin gene. Influenza A(H3N2) and influenza B viruses were isolated in 283 and 42 patients, respectively, while no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC50 value exceeding 50 nM for any of the neuraminidase inhibitors. IC50 values for A(H3N2) were similar between the 2010-2011 and 2011-2012 seasons. In contrast, the IC50 values for influenza B viruses in the 2011-2012 season to the four drugs were significantly lower than those found in the 2010-2011 season. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC50 values to increase in Japan at present.

Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial.

Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of laninamivir octanoate once daily for 2 days (LO-2), 20 mg of laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P < 0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7-85.8] and 78.1 % (95 % CI 64.1-86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20 mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts.

Increased symptom severity but unchanged neuraminidase inhibitor effectiveness for A(H1N1)pdm09 in the 2010-2011 season: comparison with the previous season and with seasonal A(H3N2) and B.

BACKGROUND: No studies of the clinical symptoms before starting therapy or of the effectiveness of neuraminidase inhibitors (NAIs) have been carried out of the 2009-2010 and 2010-2011 seasons that compare A(H1N1)pdm09 or the three circulating types of influenza virus. METHODS: The clinical symptoms and duration of fever (body temperature ≥37·5°C) after the first dose of an NAI (oseltamivir, zanamivir, laninamivir) were analyzed. PCR was carried out for 365 patients with A(H1N1)pdm09 in the 2009-2010 season and for 388 patients with one of the three types of influenza circulating in the 2010-2011 season. IC50 for the three NAIs was also analyzed in 51 patients in the 2010-2011 season. RESULTS: The peak body temperature was significantly higher in 2010-2011 than in 2009-2010 for patients under 20 years with A(H1N1)pdm09, and in the 2010-2011 season for children 15 years or younger with A(H1N1)pdm09 than for those with other virus types. The percentage of A(H1N1)pdm09 patients with loss of appetite or fatigue was significantly higher in 2010-2011 than in the previous season. The duration of fever was not affected by the kind of NAI or by age in multiple regression analysis. The percentage of patients afebrile at 48 hours after the first dose of NAI was significantly higher for A(H1N1)pdm09 than for A(H3N2) (laninamivir) or B (oseltamivir and laninamivir). CONCLUSION: Although the clinical symptoms of A(H1N1)pdm09 were slightly more severe in the 2010-2011 season, the effectiveness of the NAIs remained high in comparison with 2009-2010 and with other types of seasonal influenza.

Clinical efficacy of long-acting neuraminidase inhibitor laninamivir octanoate hydrate in postmarketing surveillance.

Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase inhibitor which requires only a single inhaled dose to fully treat infection by the influenza virus. In Japan, this drug was launched in October 2010 as a new treatment for the influenza virus. A postmarketing surveillance study was conducted in the 2010/2011 influenza season to assess the efficacy of this drug in clinical settings. For 3542 patients evaluated for efficacy (type A, n = 3179; type B, n = 342, unknown type, n = 3), including the day of drug administration, the median duration to fever resolution was three days, and the median duration to relief from influenza symptoms was four days. Based on the judgment of participating physicians, the efficacy rate was 97.6 % for type A influenza, 93.3 % for type B influenza, and 100 % in unknown types. "Treatment failure," as judged by participating physicians, was most closely correlated with the inhalation status of laninamivir. Despite laninamivir requiring only the administration of a single dose, it was confirmed to be an effective treatment in more than 90 % of patients with type A or type B influenza virus infections. This drug was considered to be useful for the treatment of influenza infections due to ease of use and its improvement of compliance. It became clear that the efficacy of laninamivir depended strongly on the status of inhalation, and thus careful and detailed instructions on the correct method of inhalation were considered to be important in order to obtain reliable therapeutic effects.