PharmaCircle PODD RC-NL Presentation 2015-10-05 · 2015. 10. 5. · Top’Ten’Products’ –...
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Trends in Drug Delivery and Formulation Injectables Tugrul T. Kararli, Ph.D., MBA President and Founder, PharmaCircle Partnership Opportunities in Drug Delivery Conference October 5, 2015
Transcript of PharmaCircle PODD RC-NL Presentation 2015-10-05 · 2015. 10. 5. · Top’Ten’Products’ –...
Trends in Drug Delivery and Formulation
InjectablesTugrul T. Kararli, Ph.D., MBA
President and Founder, PharmaCircle-‐
Partnership Opportunities in Drug Delivery ConferenceOctober 5, 2015
PharmaCircle Corporate Snapshot
• 2003 -‐ Founded– Drug delivery and formulation technology information
• 2015– Full complement of research, development, clinical, regulatory and business modules for drug and combination products, biologicals, medical devices and more
– Coverage of Rx, OTC, Generic and Veterinary products– Worldwide pipeline with details not available else where – Broadest regulatory content under a single source– Proprietary search and display technologies
Outline
• Overall trends in pharmaceutical products and pipeline
• The use of drug delivery formulation and device technologies within the injectable sector
• Alternatives to injectable delivery for biologics
Top Ten Products – WW Sales Injectables and Biologics
2004 2009 2014Product Rank Product Sales Product Sales Product Sales
1 Lipitor 11,727 Lipitor 12,651 Humira 12,543
2 Zocor 5,197 Plavix 9,455 Sovaldi 10,283
3 Plavix 5,110 Enbrel 8,489 Remicade 9,916
4 Norvasc 4,463 Advair 7,792 Enbrel 8,949
5 Zyprexa 4,420 Abilify 6,600 Lantus 8,435
6 Advair 4,019 Remicade 6,419 Abilify 8,404
7 Nexium 4,382 Diovan 6,091 Rituxan 7,553
8 Pravachol 3,679 Avastin 5,745 Advair 7,035
9 Epogen 3,589 Rituxan 5,620 Avastin 7,023
10 Prevacid 3,455 Humira 5,563 Herceptin 6,868
Total 50,041 74,425 87,009
-‐ all sales in million USD as reported by manufacturer
Top 20 Products by Sales -‐ 2014
0
2
4
6
8
10
12
14
Biotherapeutics Small Molecules
Drug Delivery Other
33%
38%
62%
DD
67%
Product and Pipeline
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
Pharma/Bio Drug Delivery Pharma/Bio Drug Delivery
Marketed Products51% Drug Delivery
Pipeline Products35% Drug Delivery
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
Marketed
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
Pipeline
Programs by Route
35% DD
24% DD
30% DD
34% DD
Programs by Molecule Type
0
2,000
4,000
6,000
8,000
10,000
12,000
Marketed
0
2,000
4,000
6,000
8,000
10,000
12,000
Pipeline
• Marketed – 20% biologics, Pipeline – 50% biologics• Proteins dominate marketed. Antibodies dominate the pipeline.
0
50
100
150
200
250
300
<50 mg 50-‐100 mg 100-‐250 mg 250-‐500 mg >500 mg
# of m
Abs
Dose
Non-‐cancer Cancer
Device and formulation technologies are needed to handle the increasing numbers of viscous antibody solution pipeline products.
*873 mAbs from Phase 1 to Marketed
Higher Antibody Doses Present a Delivery Challenge
Programs by Injection Route
0
200
400
600
800
1,000
1,200
1,400
1,600
1,800
2,000
Marketed Phase 3 Phase 2 Phase 1 Pre Clinical
IV SC IM ID All Others
• IV injection dominates• More SC Injection vs IM in Pipeline
Injectable Drug Delivery Technologies
0
200
400
600
800
1,000
1,200
Injectable Drug Delivery Pipeline
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
Nanoparticle (NP) Technologies
0
20
40
60
80
100
120
140
160
180
200
Nanoparticle Pipeline
0
100
200
300
400
500
600
700
Research Preclinical Phase 1 Phase 2 Phase 3 Registration Approved Marketed
Injectable Nanoparticle -‐ Programs by Phase
Conjugate Technologies
0
20
40
60
80
100
120
Conjugate Technologies Injectable Pipeline
050100150200250300350400450500
Injectable0Conjugates06 Products0by0Phase
Injection Systems -‐ Technologies
0
50
100
150
200
250
300
Injection Systems -‐ Pipeline
0
100
200
300
400
500
600
700
800
Research Preclinical Phase 1 Phase 2 Phase 3 Registration Approved Marketed
Injection Systems -‐ Products by Phase
Repatha – PFS & Autoinjector-‐ Amgen
• Approved in 2015 for Hypercholesterolemia• 140 mg/ml, evolocumab (MW 141 kDa) • Repatha Pen or PFS uses 27G needle, 1 ml delivered in 15 seconds• Uses Proline and low pH (5) to reduce viscosity• SureClick device modified to handle viscous solutions
Repatha Excipients-‐ Proline-‐ Glacial Acetic Acid-‐ Polysorbate 80-‐ Sodium Hydroxide-‐ Sterile Water for Injection
Novel Injection Devices (1)
Zeneo(Crossject)Disposable Needle Free
Cool-‐click2(Bespak Europe) Reusable Needle Free
YpsoPen(Ypsomed)Reusable Pen
ClickJect (BD/BMS)Disposable Autoinjector Based on BD Physioject
AXIS-‐D(Haselmeier)Disposable Pen
Lisa(Unilife)Reusable Autoinjector
Novel Injection Devices (2)
Epicard/e-‐cue(Kaleo)
GLIDE(Glide Pharma)Solid Dose Injector
Aira Heated AI (Cambridge Consultants)
Injectors
Oval Disposable AI (Oval Medical)novel primary drug containment technologies
Fill Vol.: 0.1 -‐ 10 mL Viscosity: 1100 cPs (motor oil)
Syrina Disposable Syringes & Ais(Bespak Europe)
2 mL of 200 cPs formulation can be delivered within 10 sec
Libertas (BD)3 -‐15 mL; 1-‐50 cPs
Enable (Enable Injections)2 -‐ 20 mL; 1-‐100 cPs
UNILIFE ReadyToGo3 – 30 mL; 1-‐100 cPs
Life Cycle Management -‐ AVONEXEvolution of Delivery formats
PRODUCT ApprovalYear
Formulation PrimaryPackage
Delivery Device
Needle Size Injection Site
LyophylisedKit
1996 LyophylisedPowder
Glass Vial Syringe Detached 23G 1 ¼ inch (X2)
IM
Lyophlised Kit – with Bioset
LyophylisedPowder
Glass Vial Syringe Detached 23G 1 ¼ inch
IM
PrefilledSyringe
2007 Solution Pre-‐filled syringe
Syringe Detached 23G, 1 ¼ inch
IM
Autoinjector 2012 Solution Pre-‐filled syringe
Autoinjector Attached25G, 5/8 inch
IM
SC – Injection for all forms
2013 LyophylisedPowder and solution
Vial / Pre-‐filled Syringe
Autoinjector or syringe
25G 5/8 inch
SC
Nucleic Acid Based Molecules
0
100
200
300
400
500
600
0
100
200
300
400
500
600
700
Gene Oligos siRNA mRNA miRNA
• Majority are early in development for cancer followed by Infectious diseases
• Marketed: DNA vaccines, and a few pDNA and oligonucleotides
• siRNA still a promising area if targets carefully selected
• mRNA is the latest molecule, major deals signed 2015
• Commercialization is definitely hampered by inability to effectively deliver to target tissues
Nucleic Acid Delivery
0100200300400500600700800900
0100200300400500600700
050
100150200250300350
• 75% all Injectable nucleic acid programs use DD with injection the major route
• 20% of nucleic acid programs are vaccines
• Nanoparticles (NP -‐ cationic liposomes, polymers, etc.) is the most common DD category
• Diseases of RES (liver, lung etc.) are realistic and natural targets for nanoparticles
DD Technology Deals (2007-‐2015)
0
100
200
300
400
500
600
700
Injection Oral Skin Other Transmucosal Ophthalmic Inhalation Devices
DD Deals parallels the overall pipeline injectable based products
Alternatives to injectable delivery
Oral Delivery – Has been tried and still trying – Nothing close getting to market
Inhalation– Jury is still out – Afrezza sales (q2 2015 $2M)
Poration– Very viable especially for vaccines – Amount delivered is limited
Poration Technologies and Pipeline
010203040506070
0
10
20
30
40
50
60
0102030405060708090
100
Conclusions
1. Definite shift in pipeline toward biologic based programs which must be delivered through injection– Top selling drugs are largely antibody based
2. Injection subcutaneous self delivery is becoming more prominent as convenient self injection devices are being introduced
3. Nanoparticle, prodrug and conjugate technologies will continue to advance to meet the demands of delivery for cancer programs and nucleic acid based molecules
