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Transcript of Antibiotics 10 x â€ک20 – Progress and CilO iiCommercial ... Weآ  Antibiotics 10 x...

  • Antibiotics 10 x ‘20 – Progress and C i l O i iCommercial Opportunities

    Tim JoslinTim Joslin Managing Director, Europe Defined Health

    Webinar 7thDecember 2011

  • Defined Health: Upcoming Presentations

    Defined Health is pleased to announce:

    Premier Partnering + Premier Content at These Upcoming Must-Attend Events:

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 2

  • The information in this presentation has been obtained from what are believed to be reliable sources and has been verified whenever possible. p Nevertheless, we cannot guarantee the information contained herein as to accuracy or completeness. All expressions of opinion are the responsibility of Defined Health, and though current as of the date of this report, are subject to change.

    © Defined Health, 2011

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 3

  • Agenda

    • Community RTI Opportunity? • Community Skin Infections• Community Skin Infections • Serious Hospital Infections • Biofilms • Clostridium difficile • Alternate approaches • Conclusions

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 4

  • 2004 IDSA Concerned, 2011 Progress, but 10 x ‘20?

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 5

  • Community Respiratory Infections

    • Most cause Morbidity not mortality – except in very young or elderly. • AECOPD in US ~10m diagnosed patients, 726k hospitalized, 119k deaths.g p , p ,

    • Vaccinations for HiB and Streptococcus reduce risk of infections in most vulnerable patients.

    • Community Acquired Pneumonia (CAP) with Multidrug resistant S. pneumoniae real risk. • ~6m cases in US, 1.5m patients hospitalized, 40k deaths.

    • (MR)S.aureus post-influenza a risk especially with an ever present threat of pandemic influenza.

    C t it ib d th i f b t i l i f ti tl• Current community prescribed therapies for bacterial infections mostly still effective and all are generic.

    • Is there enough medical need to support new drug development?

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 6

    Source: www.cdc..gov Morris A. et al. J. COPD 5 (1) Feb 2008:43-51, DH Insight

  • HCAP – An Independent Variable For Mortality In Pneumococcal Pneumonia

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 7

  • S. pneumoniae Resistance Continues

    • Macrolide resistance continues to be incident across all regions worldwide – most marked in Asia.

    • The varying serotypes of S. pneumoniae show different levels of invasiveness.

    • 19A and 19F are now covered by the Prevnar 13 vaccine. However it is likely that emergence of new invasive and multidrug resistant serotypes will occur with this and other developmental pneumococcal vaccines.

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 8

    Source: Bouchillon et al Poster 242 IDSA 2011, Edwards K IDSA 2011, Cowen September 2011

  • S. pneumoniae Resistance in Europe 2010

    Penicillin R+I Macrolide R+IPenicillin R+I Macrolide R+I

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 9

    Source: EARS-Net maps

  • MRSA USA300 Moving from Community to Hospitals

    • A single USA300 isolate found non-susceptible to vancomycin (MIC=3-4 μg/ml) and daptomycin (MIC=1.5 μg/ml)

    • First reports coming of MDR US300 in UK (similar to EMRSA15 a HA MRSA) indication of

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 10

    • First reports coming of MDR US300 in UK (similar to EMRSA15 a HA-MRSA) - indication of things to come?

    Source: C2-1285 ICAAC 2010, C-2 073 ICAAC 2011

  • New Agents to Treat Community RTI’s

    Attributes Required • Spectrum must include MDR S. pneumoniae, MRSA, spectrum should include atypicals

    Mycoplasma, Chlamydia, Legionella +/- serious Gram –ve pathogens P. aeruginosa, K pneumoniae to cover all agesK.pneumoniae to cover all ages.

    • Should be IV & oral with single/twice daily dosing. Paediatric use important.

    Gram +ve inc.

    RTI Gram-ve H. influenzae,

    Extended RTI Gram-ve P. aeruginosa

    Atypical Legionella,

    IV/oral

    MRSA M. catarrhalis K. pneumoniae Mycoplasma, Chlamydophila

    Omadacycline Yes Yes Yes Yes Yes

    Solithromycin Yes Yes No Yes YesSolithromycin Yes Yes No Yes Yes

    Delafloxacin Yes Yes Yes Yes Yes PDF

    GSK1322322 Yes Yes No ? Yes

    NXL103 Yes Yes No Yes Oral Only JNJ-Q2 Yes Yes Yes Yes Yes

    Finafloxacin Yes Yes Yes Yes Yes

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 11

    BC-3781 Yes Yes No Yes Yes

    Source: Company websites, DH Insight

  • Omadacycline (Paratek) • Good coverage of Gram positive blood isolates In addition to a broad spectrum of• Good coverage of Gram positive blood isolates. In addition to a broad spectrum of

    Gram positive/negative and anaerobic activity.

    • In the Phase II cSSTI study IV/oral omadacycline showed equivalence to linezolid IV/oral (CE population 98% v 93%; ME population 97% v 94%).

    • Phase III studies in CAP and ABSSSI ongoing.

    • Will this still be head to head with ceftaroline or stall due to Novartis’ departure?

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 12

    Source: PosterL1-1760 ICAAC 2010, E-1588 ICAAC 2010; DH Insight

  • Community Skin InfectionsCommunity Skin Infections

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 13

  • MRSA in Europe 2010 v 2008

    2010 2008

    Note change in UK due to political pressure and extra funding

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 14

    Source: EARS-Net maps

  • Uncomplicated Skin Infections

    • Large number of uncomplicated infections treated in the community. • Increasing incidence of CA-MRSA can limit treatment choices - >30% of skin

    infections caused by CA-MRSA. • TMX currently is effective in the majority of cases. • Linezolid oral used for the treatment failures (~10%) – restricted by cost/AE profile. • CA-MRSA resistance patterns will change – but how quickly?p g q y

    • Need for alternate oral MRSA treatments.

    • All of the RTI agents mentioned could be used for uSSTI in the community.

    • Will the level of methicillin resistance in S. aureus be enough to increase the

    medical need and support premium pricing after loss of Zyvox patent in 2016?

    • Near term - Maybe in US, unlikely in Europe.

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 15

    Source: DH Insight

  • Novel Approaches to Serious Hospital InfectionsNovel Approaches to Serious Hospital Infections

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 16

  • ESKAPE – Hit List for Hospital Acquired Infections

    • CDC implicates the following bacteria in 2/3rds of hospital acquired infections:

    • Enterococcus spp. • Staphylococcus aureus (MSSA/MRSA) • Klebsiella spp. • Acinetobacter baumannii • Pseudomonas aeruginosa • E. coli

    • This does not imply that they can not be treated with established antibiotics.

    Insight Briefing – Antibiotics 7th December 2011 © Defined Health 2011 Page 17

    Source: www.cdc.gov, DH Insight

  • Hospital Post-Surgical/Invasive Infections Improved Infection Control Natural Decline in MRSA

    • MMWR recently reported on central line acquired blood stream infections:

    • ‘In 2009, an estimated 25,000 fewer CLABSIs occurred among patients in ICUs in Year 2006 2010

    A Prospective, Multicenter Cohort Study of 351,617 Surgical Procedures: The Updated Epidemiology of Surgical Site Infection (SSI) in 25 Community

    Hospitals in North Carolina

    CLABSIs occurred among patients in ICUs in the United States than in 2001 (a 58% reduction). ‘

    • ‘Given the reported mortality from CLABSIs these reductions represent an

    No. Procedures n=63,071 n=71,429 P-value

    Organism n (%) Rate n (%) Rate

    Staph aureus 277 (29) 0 38 277 (27) 0 24 0 14CLABSIs, these reductions represent an estimated 3,000--6,000 lives saved and estimated excess health-care costs of $414 million.’ ‘ i ibi i i h

    Staph aureus 277 (29) 0.38 277 (27) 0.24 0.14

    MRSA 169 (18) 0.23 137 (13) 0.12 0.0034

    MSSA 108 (11) 0.15 142 (14) 0.13 0.24

    Gram negative org 223 (26) 0.35 249 (32) 0.35 0.88• ‘Focusing on antibiotic-resistant pathogens

    can be especially important given the increased risk for mortality.’

    org

    Coag-neg Staph 108 (11) 0.15 54 (5) 0.05

  • ESBL Driven Gram Negative Resistance Increasing • E.coli ESBL+ve continue to increase

    worldwide driven by Europe and Africa. • K.pneumoniae ESBL+ve shows similar

    trend, but with US incidence flat (2006 v

    • Decreasing susceptibility seen in Acinetobacter spp. and ESBL+ve Enterobacteriaceae spp.

    ( 2010).

    In