Date post: | 29-Nov-2014 |
Category: |
Technology |
Upload: | progueda |
View: | 212 times |
Download: | 7 times |
Has innova)on in inhala)on science run out of steam?
www.inhala(onasia.org © Copyright Inhala(on Asia 2014
Philippe Rogueda I3 -‐ Innova)on in Inhala)on -‐ 10 July 2014
Disclaimer This presenta(on contains the personal opinions and thoughts of the presenter and does not necessarily represent the opinion of Inhala(on Asia nor of any employer or company or society associated with whom the presenter might be or has been associated.
A lack of innova)on? GSK’s Breo Ellipta® efficacy for asthma undis(nguished from Advair®
Pink Sheet, 30 June 2014
COPD is currently the 4th leading cause of death worldwide, predicted to rise to be the 3rd leading cause of death by 2030
Global ini7a7ve for chronic obstruc7ve lung disease (GOLD) 2013 (www.goldcopd.org)
Only 2 new drugs to treat asthma in 15 years – antagonists to leukotriene and monoclonal an(bodies against immunoglobulin E
The global asthma report 2011 (www.globalasthmareport.org)
pMDIs s(ll command ~ 50 % of the global inhalers market
Data IMS database July 2014
Par)cle engineering Late 90’s: the par(cle engineering gold rush:
Inhale, AirX, BPD, Prosonix, NextBreath, Mannkind
2 µm
Crystalline budesonide
Pulmospheres 2009
Pulmospheres 2013
Pulmosols SAXS BPD
Par)cle engineering We were promised new and outstanding DPIs, we got Exubera!
“The key to innova(on is the execu(on”
Par)cle engineering To this day, TOBI PodHaler is the only commercialised engineered par(cle DPI on the market
Approved 22 March 2013, with patents already expired (2013/2014)
Tobramycin yearly sales (top 5 EU markets) 1Q13-‐1Q14 779,849 units: 377,658 DPI 402,191 Nebules
USD 73.5 M: 30.35 DPI 43.2 Nebules
Typically, DPI costs USD 80 per unit. Nebules are genericised. MIMS july/aug 2014:
TOBI nebules 56 ampoules £1187.20 TOBI podhaler 56 capsules £447.50
Par)cle engineering
Afrezza, inhaled insulin, Mannkind
Approved by FDA 27 June 2014
Why don’t innova)ons translate into products? pMDIs S(ll going strong despite the Montreal Protocol, despite the advent of DPI, despite all odds! No new API: formoterol, arformoterol, levalbuterol, albuterol, salbutamol, salmeterol, budesonide, ciclesonide, flu(casone, mometasone, aclidinium, (otorpium, ipatropium, indacaterol, vilanterol…and their combina(ons!... Market figures (IMS data top 5 markets UK, De, Sp, Fr, It; 1Q13-‐1Q14)
Product
Sere(de pMDI DPI
USD 635,275,062 USD 981,158,809
Spiriva HandiHaler Respimat
USD 990,104,515 USD 157,573,605
Why don’t innova)ons translate into products?
What expecta(ons should we have for innova(on in inhala(on drug delivery? Science vs. Investment Incremental vs. game changing Visible vs. Hidden
The only visible innova)ons are the products
Devices are more visible than formula)ons
Clinicians only want new molecules
Investors want tangible dreams!
1858 1st Inhaler
1864 1st Nebuliser
Medihaler 1st pMDI 1956
1987 Montreal Protocol
Turbohaler 2000
Exubera 2006
1999 Relenza 1995
Airomir 1st HFA pMDI
Spinhaler 1st DPI 1973
Inhala)on Drug Delivery Timeline
hup://www.inhala(onreport.com/2009/09/27/baule-‐of-‐the-‐mdi-‐and-‐dpi-‐patent-‐trends/
Signs of innova)on: US patents and applica)ons
Signs of innova)on: granted US patents
0
5
10
15
20
25
30
35
1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014
pMDI
DPI
nebules
nasal
Signs of innova)on: nasal publica)ons
474 hits retained: 255 USA, 46 UK, 37 De Top 3 Journals: Annals of allergy, Asthma & Immunology Allergy and asthma proceedings American journal of rhinology and allergy
No pharmaceu(cal sciences journal
15 16 19 26 22
12 14 19 22
33
19 25
18 21 18 20
33
64 67 57
4
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Signs of innova)on: DPI publica)ons
780 hits retained: 202 USA, 142 UK, 48 De Top 3 Journals: Respiratory medicine J. aerosol medicine The journal of asthma
8
21 27
40 39
54 47
41 41
59
26
42
54
41
52 56 58 65
9
Signs of innova)on: pMDI publica)ons
556 hits retained: 198 USA, 110 UK, 30 De Top 3 Journals: Respiratory medicine J. aerosol medicine The journal of asthma
3 12 9 8 8
17
29
16 27
33 43
56 44
57
40 39
21
40 32
20
2
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Visible innova)on: devices
Single dose inhalers 15 dry powder
3 nasal (2 launched) 1 HFA
Has anyone heard of the Swinghaler? Mep(n Swinghaler launched in Japan July 2014 Procaterol DPI for COPD Otsuka Co. Japan
Visible innova)on: devices
Diskus: 14 Parts
Turbuhaler: 14 Parts
Breezhaler: 10 Parts
DirectHaler: 2 Parts
Twincer: 4 Parts
Dose One: 3 Parts
The price of innova)on
£0.05 per dose for Ventolin £0.11 per dose for Flixo)de £0.3 per dose for Sere)de £0.48 per dose for Serevent £.93 per dose for Revlar Ellipta
£3 $0.3
Performance improvement: pMDI vs DPI The Montréal protocol had unintended consequences:
-‐opened the way for DPIs -‐spurred improvement in pMDI performance … the silent innova(on
FPF % pMDI DPI
Advair SX 37.8 ; FP 39.1 SX 16.7 ; FP 21.8
Symbicort FFD 54.1 ; BUD 51.4 FFD 20.7 ; BUD 23.1
Flixo(de 32.7 36.9
Pulmicort 17.7 40.7
Beclomethasone 26.8 24.3
Spiriva -‐-‐-‐ 22-‐29
Performance improvement: engineered par)cles Par(cle engineering raised the bar for DPI performances and led to improved DPI blends Devices drive performance improvement drama(cally
FPF % Engineered Blend
Prosonix -‐ FP 6 (t=0) 5.2 (t=4weeks)
7 (t=0) 3.2 (t=4weeks)
Prosonix -‐ BUD 16.5 (t=0) 16.6 (t=4weeks)
13.7 (t=0) 10.7 (t=4weeks)
iSperse -‐ undisclosed 65.1% @ 60 L/min
67.3% @ 28.3 L/min
Diskus Respira
Advair @4kPa FP 21.8 SX 16.7
FP 70 SX 78.2
References: private data and M.R. Feddah et al. J.Pharm.Pharm.Sci 3(3):317-‐324 (2000); H.R. Chapman et al. Int.J.COPD 6:335-‐363 (2011); W.Y. Tarsin et al. 316:131-‐137 (2006);Poster “Novel dual-‐chamber dry powder inhaler for combina(on therapy, M.J. Donovan, A. Gibbons, H.D.C. Smyth, J. Pappo.
What’s next? Vaccina(on Personalised medicines Non medicinal therapies Therapies for non caucasians? Asian, South American and Indian markets? An actual take off of engineered par(cles and efficient devices?
© Copyright Inhala(on Asia 2014
www.inhala(onasia.org Where West Meets East
Follow us on