dm+d

Unassigned

New Medicines

Xofluzatreatment of uncomplicated influenza in patients aged 12 years and above.

Information

Xofluza
New molecular entity
Roche
Roche

Development and Regulatory status

Launched
Approved (Licensed)
Launched
July 2021
Jul 21Launched in the UK [26].
Jul 21MHRA publishes SPC for baloxavir, which is licensed in the UK for treatment of uncomplicated influenza and post-exposure prophylaxis of influenza in individuals aged 12 years and above. The SPC indicates approval actually happened in Jun 21, although information from the company previously indicated it happened in Jan 21 [25].
May 21UK launch planned for July 2021 [24].
Jan 21Approved in UK [23].
Jan 21Licensed in EU (not UK) [22].
Nov 20Recommended for EU approval by CHMP - the full indication is "for the treatment of uncomplicated influenza in patients aged 12 years and above. Also: for post-exposure prophylaxis of influenza in individuals aged 12 years and above." It should be used in accordance with official recommendations [21].
Dec 19NDA is for indication ´treatment of influenza in patients aged 12 and above, including patients at high risk of developing influenza-related complications and for post-exposure prophylaxis of influenza in individuals aged 12´ [19].
Dec 19The EMA have received a centralised marketing authorisation application for baloxavir. [16]
Feb 19Uptake has been slow since launch in the US, partly due to its high cost, but also due to fears about resistance, with reports of ´mutant´ viral flu strains affecting efficacy of baloxavir in Japan [15].
Oct 18EU filing planned for 2019 [14].
Oct 18Approved in the US for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours [13]
Jun 18Filed in US under priority review [7]
Feb 18EU & US filings planned for 2018 [6].
Sep 17Based on the results from CAPSTONE-1, a New Drug Application is planned in Japan later this year, as is a submission to US FDA [4].
Jun 16Originated by Shionogi in Japan and licensed to Roche worldwide except Japan and Taiwan; Shionogi have it in PII trials in Japan and project a Japanese launch by Q1 2018 [1].

Category

Infectious Disease
Cap-dependent endonuclease inhibitor, inhibits the first proliferation step after viral entry into the cell
Weekly GP consultations for flu-like illness in England in 2019 ranged from 13 to 23 per 100,000 (~300 per 100,000/year), but were lower than the previous year. [17] In addition, ~17,500 prescriptions for antivirals were dispensed in primary care in England in 2019 (~30 per 100,000 people), presumably for people at risk of serious complications. [18]
treatment of uncomplicated influenza in patients aged 12 years and above.
Oral

Further information

Yes

Trial or other data

Jul 20Japanese RCT (752 household contacts of 545 index patients) found single-dose baloxavir (BL) showed efficacy in preventing influenza in household contacts of patients with influenza (clinical influenza developed in 1.9% on BL vs. 13.6% placebo; risk ratio, 0.14; 95% CI, 0.06-0.30;p<0.001) [20].
Jun 20PIII CAPSTONE-2 trial (n=2,184) found single-dose baloxavir had superior efficacy to placebo (73.2h vs. 102.3h; difference 29.1h [95% CI 14.6 to 42.8], p<0.0001) and similar efficacy to oseltamivir (81.0h; difference from baloxavir 7.7h) in time to improvement of influenza symptoms [13].
Oct 18New late-stage data released from CAPSTONE-2 trial. Baloxavir marboxil significantly reduced the median time to symptom improvement in influenza type A/H3N2 and type B to 75.4 hours and 74.6 hours, respectively, versus 100.4 hours and 100.6 hours for placebo (p<0.05). Numerically there was a shorter median time to improvement of influenza symptoms with baloxavir vs. oseltamivir (73.2 vs. 81 hours) but this was not statistically significant. This outcome mirrors a similar one from the CAPSTONE-1 study in uncomplicated influenza, where the time to alleviation of symptoms was similar between the two drugs [5,6].
Jul 18In the published PIII CAPSTONE I study (n=1436), the time to alleviation of influenza symptoms (TTAS) was shorter with a single oral baloxavir dose vs. placebo (median TTAS: 53.7 hours vs. 80.2 hours, P < 0.0001). Faster resolution of fever vs. placebo was also observed (24.5 vs. 42.0 hours, p < 0.0001) with baloxavir vs. placebo. Duration of symptoms was similar for baloxavir dose and oseltamivir (TTAS 53.5 hours vs. 53.8 hours; p=0.76) as was fever reduction (median time 24.4 hours versus 24.0 hours; p=0.92). Median time to cessation of viral shedding (determined from nasal/throat swabs) was 24 hours with baloxavir vs. 72 hours with oseltamivir (P < 0.0001) and 96 hours for placebo (P < 0.0001). [9,10]

Sep 18: CAPSTONE-1 data and editorial on influenza treatment published the the NEJM. [9,10]


Sep 17: Data from PIII CAPSTONE-1 study presented at conference. Study (n=1436) in patients with influenza reported similar time to alleviation of symptoms with S-033188 vs oseltamivir; 53.7 hours vs 80.2 hours (p<0.0001) [4].

Sep 17CAPSTONE-2 (NCT02949011) is currently recruiting in US and UK. Primary objective of this study is to evaluate efficacy of a single, oral dose of S-033188 compared with placebo by measuring time to improvement of influenza symptoms in patients with influenza at high risk of influenza complications presenting within 48 hours of symptom onset. Estimated primary completion date is Jul 18 [3].

Evidence based evaluations

Xofluzapost-exposure prophylaxis of influenza in individuals aged 12 years and above.

Information

Xofluza
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Approved (Licensed)
Launched
July 2021
Jul 21Launched in the UK [21].
Jul 21MHRA publishes SPC for baloxavir, which is licensed in the UK for treatment of uncomplicated influenza and post-exposure prophylaxis of influenza in individuals aged 12 years and above. The SPC indicates approval actually happened in Jun 21, although information from the company previously indicated it happened in Jan 21 [20].
Feb 21Approval in the US was for prevention of influenza in people 12 years of age and older following contact with someone with influenza (known as post-exposure prophylaxis) [19].
Jan 21Approved in UK [18].
Jan 21Approved in EU [17]
Nov 20Approved by US FDA. [16]
Nov 20Recommended for EU approval by CHMP - the full indication is "for the treatment of uncomplicated influenza in patients aged 12 years and above. Also: for post-exposure prophylaxis of influenza in individuals aged 12 years and above. It should be used in accordance with official recommendations [15].
Mar 20FDA accepts a New Drug Application (NDA) for a new formulation of Xofluza as one-dose granules for oral suspension (2 mg/mL), as well as two supplemental New Drug Applications (sNDA) for the treatment of acute uncomplicated influenza in otherwise healthy children aged one to less than 12 years of age who have been symptomatic for no more than 48 hours, and for post-exposure prophylaxis of influenza in people one year of age and older for both the oral suspension and currently-available tablet formulation. The FDA is expected to make a decision on these approvals by November 23, 2020 [13].
Dec 19The MAA is for indication ´treatment of influenza in patients aged 12 and above, including patients at high risk of developing influenza-related complications and for post-exposure prophylaxis of influenza in individuals aged 12´ [12].
Dec 19The EMA have received a centralised marketing authorisation application for baloxavir. [9]
Oct 19EU & US filings now expected 2019 [7].
Jun 19Data from the BLOCKSTONE trial will be shared with regulators globally for a potential new approval [2].
Apr 19EU & US filings planned for 2020 [3].

Category

Cap-dependent endonuclease inhibitor, inhibits the first proliferation step after viral entry into the cell
10 December 2019Weekly GP consultations for flu-like illness in England in 2019 ranged from 13 to 23 per 100,000 (~300 per 100,000/year), but were lower than the previous year. [10] In addition, ~17,500 prescriptions for antivirals were dispensed in primary care in England in 2019 (~30 per 100,000 people), presumably for people at risk of serious complications. [11]
post-exposure prophylaxis of influenza in individuals aged 12 years and above.
Oral

Further information

Yes

Trial or other data

Sep 19

Roche announced that PIII BLOCKSTONE study showed preventive treatment with )(baloxavir marboxil) after exposure to an infected household member significantly reduced the risk of developing flu by 86% versus placebo. The results show just 1.9% of treated household members had flu compared with 13.6% in the placebo-treated group (p<0.0001) [6].

Evidence based evaluations

Xofluzainfluenza in infants and children aged up to 12 years

Information

Xofluza
Licence extension / variation and new formulation
Roche
Roche

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Feb 21EU & US filings planned for 2021 (age 1-12 years) and 2022 (age 0-1 year) [10].
Dec 20Not approved in the US; Roche is determining the path forward with the FDA [9].
Mar 20FDA accepted new drug applications for baloxavir for the treatment of acute uncomplicated influenza in healthy children aged 1-12 years who have been symptomatic for 1 year. The target action date for these NDAs is November 23, 2020 [7].
Apr 19EU & US filings planned for 2020 [1].

Category

Cap-dependent endonuclease inhibitor, inhibits the first proliferation step after viral entry into the cell. Oral suspension formulation.
Weekly GP consultations for flu-like illness in England in 2019 ranged from 13 to 23 per 100,000 (~300 per 100,000/year), but were lower than the previous year. Rates for children appear similar to those in adults on average. [5] In addition, ~650 prescriptions for antivirals dispensed as liquids in primary care in England in 2019. [6]
influenza in infants and children aged up to 12 years
Oral

Trial or other data

Dec 19PIII MINISTONE study (NCT03653364) is still recruiting with an estimated primary completion date of Sept 2020. [3]
Oct 19Recruitment complete in miniSTONE 2 [1].
Sep 19In the PIII MINISTONE-2 study time to alleviation of influenza signs and symptoms of baloxavir was comparable to oseltamivir (median time of 138 hours vs 150 hours). Baloxavir marboxil reduced the length of time that the influenza virus continued to be released from the body by >2 days vs. oseltamivir (viral shedding; median time of 24.2 hours vs 75.8 hours, respectively. With baloxavir,46.1% experienced >1 adverse effect vs. 53.4% with oseltamivir.[4]
Jul 19Genentech announce PIII MINISTONE-2 trial hits primary endpoint [2].
Feb 19First patients expected to be enrolled in the PIII miniSTONE 1 (NCT03653364; n=30; 0-1 year) study. Xofluza will be given to healthy patients with influenza-like symptoms on day 1. Safety is the primary outcome [1].
Oct 18First patients expected to be enrolled in the PIII miniSTONE 2 (NCT03629184; n=120; 2-12 year) study. Xofluza will be compared with Tamiflu in healthy patients with influenza-like symptoms. Safety is the primary outcome [1].

Xofluzatreatment in patients at high risk of complications

Information

Xofluza
Licence extension / variation
Roche
Roche

Development and Regulatory status

Not approved
Not approved
Launched
Jul 21MHRA publishes SPC for baloxavir, which is only currently licensed in the UK for treatment of uncomplicated influenza and post-exposure prophylaxis of influenza in individuals aged 12 years and above. The SPC indicates approval actually happened in Jun 21, although information from the company previously indicated it happened in Jan 21 [18].
Jan 21The EMA did not approve Xofluza for treatment of patients at high risk of developing influenza-related complications. They concluded that the proposed indication includes a broader population than the one studied in the pivotal studies and only patients with uncomplicated influenza were included. Also the entire spectrum of high-risk patients was not studied [19].
Dec 19NDA is for indication ´treatment of influenza in patients aged 12 and above, including patients at high risk of developing influenza-related complications and for post-exposure prophylaxis of influenza in individuals aged 12´ [12].
Dec 19The EMA have received a centralised marketing authorisation application for baloxavir.
Oct 19Approved in US [8]
Mar 19The FDA has accepted a supplemental New Drug Application for baloxavir marboxil as a single-dose, oral treatment for people at high risk of complications from flu [7]
Jan 19Roche plans filings in EU & US for high risk influenza in 2019 [2].

Category

Cap-dependent endonuclease inhibitor, inhibits the first proliferation step after viral entry into the cell
Weekly GP consultations for flu-like illness in England in 2019 ranged from 13 to 23 per 100,000 (~300 per 100,000/year), but were lower than the previous year. [10] In addition, ~17,500 prescriptions for antivirals were dispensed in primary care in England in 2019 (~30 per 100,000 people), presumably for people at risk of serious complications. [11]
treatment in patients at high risk of complications
Oral

Further information

Yes

Trial or other data

Oct 18New late-stage data released from CAPSTONE-2 trial. Baloxavir marboxil significantly reduced the median time to symptom improvement in influenza type A/H3N2 and type B to 75.4 hours and 74.6 hours, respectively, versus 100.4 hours and 100.6 hours for placebo (p<0.05). Numerically there was a shorter median time to improvement of influenza symptoms with baloxavir vs. oseltamivir (73.2 vs. 81 hours) but this was not statistically significant. This outcome mirrors a similar one from the CAPSTONE-1 study in uncomplicated influenza, where the time to alleviation of symptoms was similar between the two drugs [5,6]
Jul 18CAPSTONE-2 study of single dose of oral baloxavir marboxil meets primary endpoint of reduced symptoms in people at high risk of complications from flu [4].
Sep 17CAPSTONE-2 (NCT02949011) is currently recruiting in US and UK. Primary objective of this study is to evaluate efficacy of a single, oral dose of S-033188 compared with placebo by measuring time to improvement of influenza symptoms in patients with influenza at high risk of influenza complications presenting within 48 hours of symptom onset. Estimated primary completion date is Jul 18 [3].

Evidence based evaluations

XofluzaInfluenza in hospitalised patients

Information

Xofluza
Licence extension / variation
Roche
Roche

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Feb 21Development discontinued after study did not meet primary endpoint [7].

Category

Cap-dependent endonuclease inhibitor, inhibits the first proliferation step after viral entry into the cell
Through the USISS sentinel scheme, a total of 5,505 hospitalised confirmed influenza cases (mean weekly incidenceof 2.10 per 100,000 trust catchment population) were reported from 24 participating sentinel NHS acute trusts across England from week 40 2018 to week 15 2019. [4]
Influenza in hospitalised patients
Oral

Trial or other data

Nov 20Results from FLAGSTONE study found that the time to Clinical Improvement (defined as Time to Hospital Discharge OR Time to NEWS2 score of ≤ 2 maintained for 24 hours up to day 35) which was the primary outcome measure, was 97.5 hours with baloxavir vs. 100.2 hours with placebo (p=0.4666). [6]