A120426T1541-79501-SWE-5A
This presentation is the property of its rightful owner.
Sponsored Links
1 / 38

A120426T1541-79501-SWE-5A PowerPoint PPT Presentation


  • 84 Views
  • Uploaded on
  • Presentation posted in: General

A120426T1541-79501-SWE-5A. FLUENZ A Live Attenuated Influenza Vaccine (LAIV). Agenda. FLUENZ Product characteristics Indication Mode of Action Others Efficacy Safety Practical information. Product characteristics. FLUENZ. FLUENZ nasal spray, suspension

Download Presentation

A120426T1541-79501-SWE-5A

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


A120426t1541 79501 swe 5a

A120426T1541-79501-SWE-5A


Fluenz a live attenuated influenza vaccine laiv

FLUENZ A Live Attenuated Influenza Vaccine (LAIV)


Agenda

Agenda

  • FLUENZ

    • Product characteristics

      • Indication

      • Mode of Action

      • Others

    • Efficacy

    • Safety

    • Practical information.


Product characteristics

Product characteristics


Fluenz

FLUENZ

  • FLUENZ nasal spray, suspension

  • Influenza vaccine (live attenuated nasal)

  • Trivalent (A/H1N1, A/H3N2, B)

  • 0.2 mLintranasal spray (0.1 mL pernostril)

  • Contains no preservatives (e.g., no thimerosal) or adjuvants (e.g. alum or squalene)

  • Storage at 2-8 ºC

  • Approved in U.S., Hong Kong, South Korea, Israel, UAE, Macau for 2-49 years, Canada for 2-59 years, Europe for 2-17 years.

  • FLUENZ /FluMist has been used in the US since 2003.

Ref. SmPC FLUENZ

5


Fluenz smpc

FLUENZ SmPC

Therapeutic indication

FLUENZ is indicated for the prophylaxis of influenza in individuals 24 months to less than 18 year of age

The use of FLUENZ should be based on official recommendations

Ref. SmPC FLUENZ


Special warnings precautions

FLUENZ SmPC

Special warnings & precautions

Contraindications

Should not be administered to children

  • with severe asthma or active wheezing as not adequately studied

    Vaccine recipients should attempt to avoid close association with severely immunocompromised individuals

Children and adolescents:

hypersensitivity to:

the active substances, any of the excipients, gentamicin or to egg proteins

Children and adolescents:

clinically immunodeficient due to conditions or immunosupp. therapy

receiving salicylate therapy

For additional information, see SmPC

Ref. SmPC FLUENZ


Extensive documentation behind ema approval

Extensive documentation behind EMA approval

  • Clinical efficacy or immunogenicity data from 43 studies

    • > 64.000 subjects

    • 31 studies includedpaediatricsubjects

  • Efficacy in paediatricsubjectswereassessed in 9 studies:

    • > 20.000 children

    • 6 placebo-controlled

    • 3 TIV (trivalentinactivatedinfluenzavaccine) controlled

  • Safety data

    • > 28,500 subjects 2 to 17 years of age from clinical studies

    • > 52,500 children and adolescents from post authorisationsafety studies

  • Flumist on the US market since 2003. > 39 million doses have been distributed

  • Fluenz Summary of Product Characteristics, http://www.ema.europa.eu, 2011-03-17

    Assessment report Fluenz, 2011-09-26

    http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/

    human/001101/WC500103711.pdf

    AstraZeneca


    Mode of administration

    Mode of administration

    • LAIV vaccine is sprayed directly into the nasal cavity1

      • Needle-free

      • Active inhalation/sniffingnot required

    • Intranasal administration enables induction of immunity at the site of virus entry2

      • Induces a broad innate, mucosal and systemic response2

      • Designed to more closely mimic the immune response generated by wild-type influenza2

    • FLUENZ SmPC

    • Tosh P et al. Mayo Clin Proc 2008; 83: 77–84.


    Types of influenza vaccine approved in the eu

    TIV

    Trivalent inactivated influenza vaccine, intramuscular

    HA is the only standardised component; other antigens may be present1,2*

    Types of influenza vaccine approved in the EU

    LAIV

    Live attenuated influenza vaccine, intranasal

    Attenuated vaccine with multiple antigens3,4*

    HA

    NA

    HA

    HA

    HA

    NP

    HA: haemagglutinin; M1, M2: matrix proteins; NA: neuraminidase; NP: nucleoprotein.

    *Image adapted from: Clinical Virology. 6th ed. 1997:911–942.4

    Please refer to the specific prescribing information for each manufacturer’s influenza vaccine as not all influenza vaccines are indicated for all ages

    1. Fluarix [Summary of Product Characteristics]. GlaxoSmithKline plc.

    2. Fluvirin [Summary of Product Characteristics]. Novartis Vaccines and Diagnostics Ltd.

    3. FLUENZ SmPC

    4. Hayden FG et al. Clinical Virology. 6th ed. 1997;911–942.

    CONFIDENTIAL – For Internal Use Only


    Laiv is engineered to prevent influenza infection

    LAIV is engineered to prevent influenza infection

    Attenuated virus: disease-causing properties removed so as not to cause illness

    Cold-adapted: replicates efficiently only in the cooler areas of the nasopharynx

    Temperature-sensitive: does not replicate efficiently in warmer areas of the lower respiratory tract where influenza viruses typically replicate

    • Cox RJ, et al. Scand J Immunol. 2004;59:1-15

    • SmPC FLUENZ

    • 3. Assessment report Fluenz, 2011-09-26

    • 4. Maassab HF, DeBorde DC. Vaccine. 1985b;3(5):355-369


    Fluenz creates a broad immune response

    FLUENZ creates a broad immune response.

    Mucosal and systemic immune response

    • mucosal IgA, systemic IgG and influenza specific T-cells2)

  • Resembles natural response to infection- engineered not to cause disease1

  • 1. Cox RJ, et al. Scand J Immunol 2004;59:1-15.

    2. Tam JS, et al. Pediatr Infect Dis J 2007;26(7):619-628

    3. Ambrose C, et al. Pediatri Infect Dis J 2008; 27:744-8.

    4. Honolulo HI, Halloran ME, et al. Am J Epidemiol. 2003;158:305-311

    5. Gaglani M, et al. Pediatr Infect Dis J 2001;20:1155-1160

    6. Fluenz: EPAR – Public assessment report. Published: 17/03/2011


    Efficacy

    Efficacy


    Key studies conducted in children placebo controlled trials

    Key studies conducted in children* – Placebo-controlled trials

    *LAIV is not approved for children under 24 months of age

    Ref. FLUENZ SmPC


    Summary of 6 randomized studies high fluenz efficacy in pediatric population

    Summary of 6 randomized studies:High FLUENZ efficacy in pediatric population.

    Efficacy of one and two doses of LAIV vs. placebo on

    culture-confirmed influenza for antigenically similar subtypes

    60% reduction

    (95% CI: 51, 68)

    77% reduction

    (95% CI: 72, 80)

    87% reduction

    (95% CI: 81, 90)

    16

    14.6%

    14.5%

    14

    12.6%

    12

    Placebo

    LAIV

    10

    Incidence of influenza

    (matched strains), %

    8

    5.7%

    6

    4

    3.1%

    1.6%

    2

    0

    One dose in first season

    (previously unvaccinated)

    Two doses in first season

    (previously unvaccinated)

    Revaccination with one dose in second season(previously vaccinated)

    *LAIV is not approved for children under 24 months of age

    Rhorer J et al. Vaccine 2009; 27: 1101–1110.


    Key studies conducted in children tiv controlled trials

    Key studies conducted in children* – TIV-controlled trials

    *LAIV is not approved for children under 24 months of age

    FLUENZ [Summary of Product Characteristics]. AstraZeneca Ltd.


    Higher efficacy relative to tiv for all strains regardless of match

    Higher efficacy relative to TIV for all strains regardless of match

    3 randomised studies: all strains regardless of match13,000 children 6 months to 17 years*

    55% reduction

    (95% CI: 45, 63)

    52% reduction

    (95% CI: 25, 71)

    32% reduction

    (95% CI: 1, 54)

    10

    9

    8.6%

    8

    TIV

    LAIV

    7

    6.6%

    6

    5.8%

    Incidence of influenza

    (matched strains), %

    5

    4.5%

    3.9%

    4

    2.8%

    3

    2

    1

    0

    6–59 months1

    6–71 months2

    6–17 years3

    Age

    *LAIV is not approved for children under 24 months of age

    1. Belshe RB et al. New Engl J Med 2007; 356: 685–696.

    2. Ashkenazi S et al. Pediatr Infect Dis J 2006; 25: 870–879.

    3. Fleming D et al. Pediatr Infect Dis J 2006; 25: 860–869.


    Mismatched strains comparison of laiv vs placebo or tiv

    Mismatched strains: Comparison of LAIV vs. placebo or TIV

    Incidence of culture-confirmed influenza in children aged 6–85 months* in

    2 randomised studies

    86% reduction

    in attack rate

    (95% CI: 75, 92)

    79% reduction

    in attack rate

    (95% CI: 71, 86)

    6% reduction

    in attack rate

    (95% CI: −32, 33)

    14

    11.6%

    12

    Placebo recipients

    LAIV recipients

    TIV recipients

    10

    8

    Incidence of culture-confirmed influenza, %

    4.5%

    6

    4

    1.8%

    1.7%

    1.6%

    2

    0.9%

    0

    Mismatched

    A/H3N2 (1997/1998)

    Study AV006

    Mismatched

    A/H3N2 (2004/2005)

    Study CP111

    Mismatched B

    (2004/2005)

    Study CP111

    26–85 months1

    6–59 months2

    6–59 months2

    • *LAIV is not approved for children under 24 months of age

    • Belshe RB et al. J Pediatr 2000; 136: 168–175.

    • Belshe RB et al. N Eng J Med 2007; 356: 685–696.


    Cochrane review efficacy laiv and tiv

    Cochrane reviewEfficacy LAIV and TIV.

    Children > 2 år

    Cochrane review: Jefferson et al. Vaccines for preventing influenza in healthy children.

    Cochrane Database Syst Rev. 200816;(2):CD004879


    Fluenz has shown to protect over time

    FLUENZ has shown to protect over time

    • FLUENZ gave 73% efficacy against matched influenza strains over a 12 months period1,2

    • FLUENZ protected against late influenza outbreaks 2

    1. Ambrose C, et al. Pediatri Infect Dis J 2008;27:744-748

    2. Tam J, et al. Pediatr Infect Dis J 2007;26:619-628

    3. Fluenz SmPC


    Laiv shows an increase in efficacy over time relative to tiv

    LAIV shows an increase in efficacy over time relative to TIV

    Efficacy by time post-vaccination versus placebo; matched strains

    • In 3 TIV-controlled studies, the relative efficacy of LAIV versus TIV for matched strains increased with time in each study

    • Results are best explained by a decline in TIV efficacy over time

    4

    0–4 months

    Relative efficacy (95% CI):34% (3, 55)

    >4–8 months

    Relative efficacy (95% CI):62% (42, 76)

    3

    TIV

    LAIV

    Incidence, %

    2

    1

    0

    0

    1

    2

    3

    4

    5

    6

    7

    8

    Time from first vaccination to influenza illness (months)

    Adapted from Ambrose CS et al, 2010

    Ambrose CS et al. Pediatr Infect Dis J 2010; 29: 806–811.


    Safety

    Safety


    Comparable safety to placebo in children aged 2 17 years of age

    Comparable safety to placebo in children aged 2–17 years of age†

    Solicited reactogenicity events days 0–10

    post-vaccination in year 1 of placebo-controlled studies

    70

    *

    60

    LAIV dose 1

    Placebo dose 1

    LAIV dose 2

    Placebo dose 2

    50

    40

    Incidence, %

    30

    *

    20

    *

    *

    10

    0

    Chills

    Cough

    ≥38.0C

    ≥39.0C

    ≥40.0C

    Vomiting

    Irritability

    Headache

    Sore throat

    Muscle ache

    Abdominal pain

    Decreased activity/tiredness

    Runny/stuffy nose

    Decreased appetite

    Fever

    Adapted from Ambrose CS et al, 2011

    †Data available from 14 placebo-controlled studies.

    *Statistically significant difference (p<0.05).

    Ambrose CS et al. Influenza Other Respi Viruses 2011; DOI: 10.1111/j.1750-2659.2011.00243.x.


    Comparable safety to tiv in children aged 2 17 years of age

    Comparable safety to TIV in children aged 2–17 years of age†

    Solicited reactogenicity events days 0–10

    post-vaccination in year 1 of TIV studies

    70

    *

    60

    LAIV dose 1

    TIV dose 1

    LAIV dose 2

    TIV dose 2

    50

    *

    40

    Incidence, %

    30

    20

    *

    10

    0

    Chills

    Cough

    ≥38.0C

    ≥40.0C

    ≥39.0C

    Vomiting

    Irritability

    Headache

    Sore throat

    Muscle ache

    Abdominal pain

    Decreased activity/tiredness

    Runny/stuffy nose

    Decreased appetite

    Fever

    Adapted from Ambrose CS et al, 2011

    †Data available from six TIV-controlled studies.

    *Statistically significant difference (p<0.05).

    Ambrose CS et al. Influenza Other Respi Viruses 2011; DOI: 10.1111/j.1750-2659.2011.00243.x.


    Study p515 asthma exacerbations within 42 days of vaccination with laiv or tiv

    Increased

    Asthma

    Unscheduled

    medication

    exacerbations

    clinic visits

    Study P515: asthma exacerbations within 42 days of vaccination with LAIV or TIV

    • The incidence of asthma exacerbations were comparable between groups

    • No significant differences were observed between treatment groups in mean PEFR findings, asthma symptoms scores, or night-time awakening scores

    Asthma exacerbations occurring

    within 42 days of vaccination with LAIV or TIV

    TIV

    LAIV

    14

    12.0

    11.8

    11.6

    11.4

    12

    10

    8.3

    7.7

    8

    Incidence (%)

    6

    4

    2

    0.3

    0.3

    0

    Hospitalisation

    Adapted from Fleming D et al, 2006

    PEFR: Peak expiratory flow rate.

    Fleming D et al. Pediatr Infect Dis J 2006; 25: 860–869.


    Fluenz smpc adverse reactions

    FLUENZ SmPC Adverse reactions


    Summary

    Summary

    • Offer a novel administration well suited for children

    • Superior efficacy vs traditional influenza vaccines among pediatric populations.

      • Both during match and mismatch seasons.

      • Shown protection over time (12 months).

    • Protects at the site entry of influenza virus. Designed to trigger a broad immunity: IgA, IgG antibodies and T-cellular immune response.

    • Well documented with safety aligned with traditional influenza vaccine.

      • Used in US since 2003 with > 39 million doses distributed.

      • Experience from seasonal and pandemic setting within pediatric population without safety issues.


    Practical information

    Practical Information


    Administration others

    Administration & others

    FLUENZ is supplied as a single-use, pre-filled intranasal spray device, containing a 0.2 ml dose. 10-pack.

    FLUENZ must be administered by a Healthcare Professional

    • The patient should breathe normally

      There is no need to readminister if:

    • FLUENZ drips out of the nose

    • The patient sneezes

    • The patient blows their nose

      Shelf life

  • 18 weeks from distribution date; expiration date is listed on the sprayers

  • Ref. SmPC FLUENZ


    Back up

    Back up


    Fluenz smpc contraindications

    FLUENZ SmPCContraindications

    FLUENZis contraindicated in children and adolescents with hypersensitivity to the active ingredients, any excipients, gentamicin, to eggs or to egg proteins

    FLUENZis contraindicated for children and adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high dose corticosteriods

    FLUENZ is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency

    FLUENZis contraindicated in children and adolescents receiving salicylate (e.g. aspirin) therapy because of the association of Reyes syndrome with salicylates and wild-type influenza infection

    Ref. SmPC FLUENZ


    Fluenz smpc special warnings and precautions

    FLUENZ SmPCSpecial warnings and precautions

    As with most vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of FLUENZ.

    FLUENZ should not be administered to children and adolescents with severe asthma or active wheezing because these individuals have not been adequately studied in clinical studies.

    Note: FLUENZ is NOT contraindicated for children mild or moderate asthma

    Do not administer FLUENZ to infants and toddlers younger than 12 months. In a clinical study, an increase in hospitalisations was observed in children younger than 12 months after vaccination. It is not recommended to administer FLUENZ to infants and toddlers 12-23 months of age. In a clinical study, an increased rate of wheezing was observed in children 12-23 months of age after vaccination.

    Vaccine recipients should be informed that FLUENZ is an attenuated live virus vaccine and has the potential for transmission to immunocompromised contacts. Vaccine recipients should attempt to avoid, whenever possible, close association with severely immunocompromised individuals (e.g. bone marrow transplant recipients requiring isolation) for 1-2 weeks following vaccination.

    No data exist regarding the safety of intranasal administration of FLUENZ in children with unrepaired

    craniofacial malformations.

    FLUENZ should under no circumstances be injected.

    Ref. SmPC FLUENZ


    Asthma documentation

    Asthma documentation

    There are several studies in children with asthma.  

    • The Fleming study: LAIV vs TIV. N= 2 211 Children (6-17 y) with mild-moderate asthma.

      • Results: LAIV higher efficacy vs TIV with comparable safety.

    • The Ashkenazi study: LAIV vs TIV. N= 2187 . Young children (6-71 months) with history of wheezing (46%) and asthma (23%).

      • Results: LAIV higher efficacy vs TIV with comparable safety.

    • The Redding study: LAIV vs placebo. N= 48. Children (9 - 17 y) with moderate to severe asthma.

      • Results: comparable safety.

    • EMA: safety has been established in children of all ages with mild to moderate asthma.  Not sufficient data on children with sever asthma.

    Ref:

    Ashkenazi S et al Pediatr.Infect.Dis.J. 2006 Oct;25(10):870-879.

    Fleming DM et al. Pediatr.Infect.Dis.J. 2006 Oct;25(10):860-869

    Redding et al Pediatr Infect Dis J, 2002;21:44–8.

    EMA Assessment report FKUENZ


    Recommendations in other countries

    Recommendations in other countries.


    Fluenz smpc undesirable effects

    FLUENZ SmPC Undesirable effects

    Not indicated in children < 24 months of age due to increased risk of wheezing post vaccination


    Summary of adverse events in children aged 2 6 years

    Summary of adverse events in children aged 2- 6 years

    *Most common adverse reactions (≥10% in LAIV and at least 5% greater than in control) are runny nose or nasal congestion and fever >37,8°C in children 2-6 years of age

    Studies reflect the data collected between 2 pooled studies and 1 active-controlled study

    1. Belshe, et al. N Engl J Med, 338:1405, 1998. 2. Tam, et al. PediatrInfect Dis J, 26:619, 2007. 3. Belshe, et al. N Engl J Med, 356:685,2007.


    Rates of wheezing in children through 42 days following vaccination

    Rates of wheezing in children* through 42 days following vaccination

    • A small but significant increase in wheezing after LAIV vs. TIV was observed in children aged 6–23 months, but there was no significant difference in children aged ≥2 years

    Medically significant wheezing rates by age

    Percentage of subjects with

    medically significant wheezing

    Adapted from Belshe R et al, 2008

    • *LAIV is not approved for children under 24 months of age

    • †Age at time of first vaccine dose

    • Belshe RB et al. Vaccine 2008; 26S: D10–D16.


    Increased hospitalizations observed in children 6 11 months of age through 180 days

    Increased hospitalizations observed in children 6-11 months of age through 180 days

    • Rates of hospitalisation for any cause were only higher amongst LAIV recipients aged 6–11 months*

    Hospitalisation rates by age

    TIV

    p=0.002

    7

    LAIV

    6

    5

    4

    Incidence (%)

    3

    2

    1

    0

    6–11

    12–23

    24–35

    36–47

    48–59

    Age (months)

    Adapted from Belshe R et al, 2007

    *LAIV is not approved for children under 24 months of age

    Belshe RB et al. N Eng J Med 2007; 356: 685–696.


  • Login