Geriatric Rounds:
Compounds of Medical Need
March 28, 2014
Albert Giovenella, Ph.D.
Adjunct Asst. Professor of Medicine
My Background at Penn
(Disclosure Slide)
•
•
•
•
•
•
1978-1981 Mycobacterial Laboratory Supervisor (H.U.P.)
1980-1987 Ph.D. Studies
1988-1992 Instructor of self-written course (Grad. Sch. of Education)
1994- Instructor, School of Dental Medicine
1995-1997 Adjunct Asst. Prof. (Geriatrics – Risa Mourey)
2007- Pres Adjunct Asst. Prof. (Geriatrics – Jerry Johnson)
• Other:
–
–
–
–
–
1970-1976 Army National Guard
1976-1978 Grad. Teaching Asst for Master’s Degree – West Chester University
1982-1988 Smithkline Beecham
1988-2008 Merck & Co.
1996
Founder Of PA Osteoporosis Society
Complete Total of NMEs (U.S. Approved)
Only
(Rolling Total By 10-year segments)
NMEs
Best straight line
350
300
250
(193 at
beginning of
2014)
The Biotech Effect
200
150
100
50
19
64
19 -19
66 73
19 -19
68 75
19 -19
70 77
19 -19
72 79
19 -19
74 81
19 -19
76 83
19 -19
78 85
19 -19
80 87
19 -19
82 89
19 -19
84 91
19 -19
86 93
19 -19
88 95
19 -19
90 97
19 -19
92 99
19 -20
94 01
19 -20
96 03
19 -20
98 05
20 -20
00 07
20 -20
02 09
20 -20
04 11
-2
01
3
0
Source: Drugs/FDA Website as of March 28, 2014
Copyright: A. Giovenella, 2009
Drug Development Strategy Grid
Pre-Approval
$
5+
Approval Window
(DiMasi Window)
Post-Approval
4+
3+
Average Approval Time
8-12 years
2+
+
-
X
$800 mil-----$1.2 bill.
Average R&D
Investment
5
20
10
Copyright: A. Giovenella, 2009
15
Exclusivity Data from DiMasi, Tufts, Sep 2009;
Approval Window Data from Tufts, 2007
Generic Presence in 2008 Prescriptions
0%
Branded
37%
Generic
63%
Source: IMS Data as of February, 2008
Generic Presence in 2013 Prescriptions
0%
Branded
16%
Generic
84%
Source: Kaiser Health News as of May 9, 2012
Copyright: A. Giovenella, 2009
Evolved Alternative Pathway for the Drug Discovery Process
Traditional Drug Research
Pathway for Pharma
LC
(Pharma)
Laboratory
Discovery
(In-vitro)
Pre-Clinical
Research
Phase I
Phase II
II a
Increasing Risk to Adverse
(Unmanageable) Levels
SC
(Biotech)
Laboratory
Discovery
(In-vitro)
Pre-Clinical
Research
Phase I
Phase II
NDA
II b
Optimal Range
of Compound
Acquisition
Phase III
Phase III or
Post-Approval
(Drug
Acquisition or
Licensing –
Biotech
Acquisition Drug
Research Pathway Looking for Exit Strategy
Copyright: A. Giovenella, 2010
Phase III
Managing Risk
or Company
Acquisition)
FDA CDER & CBER
Breakthrough Therapy Designations
In the FDA SIA (Safety and Innovation Act) of 2012, in Section 902, the
FDA allowed for BREAKTHROUGH THERAPY DESIGNATIONS in order to
expedite development and review of drugs for life-threatening and serious
diseases.
In order for the sponsor to receive this designation for a drug in
development, the sponsor must show:
1) Evidence that the drug is intended, alone or in combination with
one or more other drugs, to treat a serious or life-threatening disease or
condition, and
2) Preliminary clinical evidence indicating that the drug may
demonstrate substantial improvement over existing therapies on one or more
clinically significant endpoints, such as substantial treatment effects
observed early in clinical development.
Source:
http:orphandruganaut.wordpress.com/2013/12/23/fda-breakthrough-therapydesignation-2013
FDA CDER & CBER
Breakthrough Therapy Designations
(As of March, 2014)
Small
Molecules Biologics Vacc
GSK
Novartis
Roche Pharmacy Vertex
USA
Other Countries
29
5
4
4(1)
2(1)
3
22
13
Phase I
2
Phase II
10
NDA Sub
1
Appr
5
Kinase Inh
7
1
Phase III
16
4
Polym/Prot
4
B Cell Targets
2
CFTR
3
Mkt Cap ($)
Therap Area
Disease State
Approved:
>200 BN
150-200
100-150
76-100
51-75
26-50
11-25
1-10
<100 MIL
PRIV
Oncology
14
Anti-infective 8
Respiratory
3
Metabolism
3
Muscle
2
Neurology
1
Cardiology
1
Dermatology
1
Hematology
2
Cancer
14
Hepatitis C
4
Cyst Fibrosis 3
Year
2013
Therap Area
Oncology
Oncology
Anti-infective
Company
Pharmacyclics / J&J
Roche (Genentech)
Gilead
2014
Oncology
Respiratory
Pharmacyclics / J&J
Vertex
Copyright: A. Giovenella, 2013
4
5
8
3
2
---5
3
2
3
FDA Breakthrough Therapy Web Page,
March 28, 2014
Other Diseases Targeted by Breakthrough
Therapy Drugs
•
•
•
•
•
•
•
•
•
•
•
Hepatitis C (3 entries)
Cystic Fibrosis (2 entries)
Duchenne Muscular Dystrophy
Malaria (Plasmodium vivax)
Bleeding Disorder from Factor Xa inhibitors
Molybdenum Cofactor Deficiency Type A
Sporadic Inclusion Body Myositis
Lysosomal Acid Lipase Deficiency (Wolman Dis)
Epidermolysis Bullosa
Lambert-Eaton Myasthenic Syndrome
Bacterial Meningitis Type B
14 Oncology (4 B)
8 Antiinfective
3 Metabolism
3 Respiratory
2 Muscle (1 B)
1 Neurology
1 Cardiology
1 Dermatology
2 Hematology
0 GI
0 Anti-inflammatory
0 OB-GYN
0 Anesthesiology
0 Analgesic
0 Bone
5 BIOLOGICS (inc)
Breakthrough Designations
by Therapeutic Area in U.S.
Since 2013
N = 35
TOTAL =
40
29
6
35
1
30
5
25
2
2
20
3
1
1
6
15
1
10
12
5
1
1
2
2
0
2013
Oncology
Neurology
2014
(Jan-Mar)
Anti-infective
Cardiology
Hematology
Metabolism
2013 - 2014
Copyright: A. Giovenella, 2014
Muscle
Respiratory
BIOLOGICS
Dermatology
Source: FDA Database, PharmaLive, Evaluate Pharma
& A. Giovenella
March 28, 2014
Onc-13 (2): Onc-14 (1) 14 Oncology (4 B)
AI-13
6 Antiinfective
Breakthrough Designations
by Therapeutic Area in U.S.
Since 2013
3 Metabolism
Resp-14 (1) 3 Respiratory
2 Muscle (1 B)
1 Neurology
1 Cardiology
1 Dermatology
2 Hematology
0 GI
0 Anti-inflammatory
0 OB-GYN
0 Anesthesiology
0 Analgesic
0 Bone
5 BIOLOGICS (inc)
N = 35
TOTAL =
40
29
6
3
2
1
1
2
2
1
2
1
1
2014
2013A
35
1
30
5
25
2
2
20
3
1
1
Resp-14 (1)
AI-13 (1)
6
15
1
Onc-13 (2)
Onc-14 (1)
10
12
5
0
2013
Oncology
Neurology
(Jan-Mar)
Anti-infective
Cardiology
Hematology
Metabolism
2013 - 2014
Copyright: A. Giovenella, 2014
2014A
(Jan-Mar)
Muscle
Respiratory
BIOLOGICS
Dermatology
Source: FDA Database, PharmaLive, Evaluate Pharma
& A. Giovenella
March 28, 2014
2013:
4 mo – Hepatitis C
$ 91.3 B MC
6 mo – Chron Lym Leuk $ 171.7 B MC
7 mo – Mantle Cell Lymph $ 263.2/$9 B MC
2014:
10 mo – Chron Lym Leuk $ 260.4 B/ $10.1 B
13 mo – Cyst Fibro (8 mut) $ 20.0 B
Time from Designation
to Approval
Since 2013
(Ph III) A-I (Gild)
(Ph III) Onc (Roch)
(Ph III) Onc (Ph/J&J)
(Ph III) Onc (Ph/J&J)
(Ph III) Resp (Vtx)
N=5
TOTAL
APPR =
25
3
2
20
13
15
7
10
6
5
10
4
0
2013
2014
(Jan-Mar)
Hep C
CLL
Mtl Cell Lym
2013 - 2014
Copyright: A. Giovenella, 2014
Cyst Fib
Source: FDA Database, PharmaLive, Evaluate Pharma
& A. Giovenella
March 28, 2014
1 > 250 B
3 201-250 B
5 151-200 B
8 101-150 B
3 76-100 B
2 51-75 B
0 26-50 B
5 11-25 B
3 1-10 B
1 751-999 M
0 501-750 M
0 251-500 M
0 101-250 M
1 100 M or less
3 PRIV
Breakthrough Designations
by Market Cap in U.S.
Since 2013
N = 35
TOTAL =
35
29
6
30
3
1
1
3
25
20
4
0
2
2
15
10
5
5
5
0
2
1
1
1
3
1
2013
2014
(Jan-Mar)
>250 B
1-10 B
201-250 B
751-999 M
151-200 B
501-750 M
101-150 B
251-500 M
76-100 B
101-250 M
2013 - 2014
Copyright: A. Giovenella, 2014
51-75 B
100 M or less
26-50 B
PRIV
11-25 B
Source: FDA Database, PharmaLive, Evaluate Pharma
& A. Giovenella
March 28, 2014
3 NSCLC
3 CLL
2 Breast
1 MM
1 AML
1 Melanoma
1 NHL
1 Mantle Cell Lym
1 Waldenst Macrog
1 SLL
1 Non-spec
0 Prostate
0 Liver
0 Pancreatic
0 Brain
Breakthrough Designations
by Oncology (Types of Cancer) in U.S.
Since 2013
N = 16
TOTAL =
16
14
14
2
2
1
1
1
1
2014
2013A
1
1
1
12
MCL-13
1
1
10
1
1
8
2
6
1
4
3
CLL-13
CLL-14
2
2
0
2013
NSCLC
NHL
(Jan-Mar)
CLL
AML
Breast
Mult Myel
Melanoma
2013 - 2014
Copyright: A. Giovenella, 2014
SLL
MCL-13
CLL-13
CLL-13
1
2014A
(Jan-Mar)
Waldenst Macrog
Mantle Cell Lym
Non-spec
Source: FDA Database, PharmaLive, Evaluate Pharma
& A. Giovenella
March 28, 2014
Summary
• As biomedical research continues, the FDA has made the
“Breakthrough Therapy Designation” (BTD) to expedite
development & approval in areas of medical need.
• Approval times for first 5 BTD approvals range from 4
months to 13 months since receiving the designation.
• Oncology research is the dominant therapeutic area
receiving BTD thus far.
• In this oncology research, the most BDT designations---and approvals are for chronic lymphocytic leukemia.