CDER New Drugs Program: 2017 Update Patrick Frey Chief of Staff Office of New Drugs, CDER/FDA
FDA/CMS Summit December 5th, 2017
Introduction
Housekeeping Data and analyses presented reflect latest information, although usual QC for official FDA reports has not occurred. Presentation content should be considered preliminary. Pay close attention to fiscal year (FY), calendar year (CY), or academic year (AY) and cut-off dates on data presentations; denominators are important too! Talented staff at FDA provide the data and analyses for this talk each year. Special thanks and acknowledgement to:
– Nader Qassim, Nancy Maizel, and Reza Kazemi-Tabriz in CDER’s Office of Program and Strategic Analysis – Mike Lanthier in the Office of the Commissioner 2
Introduction
Topics to be covered
New drug review process efficiency: a historical look and changes in PDUFA VI New drug activity in 2017: approvals, workload, international comparisons, and profiling the 2017 class of NMEs/BLAs Development phase activity: IND workload, the breakthrough program, meeting workload and changes in PDUFA VI A look ahead to 2018 3 •3
New Drug Review Process Efficiency
CDER New Molecular Entity Approval Rates by PDUFA Cohort 100% 90%
PDUFA V
% NMEs Receiving Approval
80% 70%
PDUFA IV
60% 50%
PDUFA I-III
40% 30% 20%
Pre-PDUFA
10% 0%
6
12
Pre-PDUFA (1988-1992)
18
24
30 36 Elapsed Time (months)
PDUFA I-III
PDUFA IV
42
48
54
PDUFA V (receipts through 3/31/2016)
* PDUFA V estimates based on 77 NMEs submitted in FY 2013 – mid FY 2015 (it is too early to estimate performance for later submissions) Projection estimates account for actions to date and elapsed time to date for non-approvals Data as of 9/30/16
4
New Drug Review Process Efficiency
NME Review Program
PDUFA V established a new review model for NME NDAs and original BLAs that had three main features: − Specified touchpoints during review for FDA-applicant communication [i.e., midcycle communication, late-cycle meeting (LCM)] − Additional time for FDA review − Independent contractor (Eastern Research Group) evaluations
Highly successful program – a conclusion shared by industry, FDA, and ERG Changes in PDUFA VI − Flexibility: FDA and applicant may agree on a Formal Communication Plan; codified treatment of expedited reviews; LCMs may be held by phone rather than F2F − Application orientation meetings are envisioned as part of a communication plan − Advisory committee meetings may be scheduled slightly later in the review process; FDA and applicant have option for informal teleconference to debrief on AC feedback
Review Program is now applied to biosimilar applications in BsUFA II
5
New Drug Activity in 2017
New Drug Activity in 2017
In CY 2017 so far*, CDER has approved 40 NMEs, including 17 orphan drugs – Record number of orphan indications approved across all NDAs and BLAs (not just NMEs and BLAs) – US continues to lead the world in first approval of NMEs
In FY 2017, new applications increased across the board for CDER compared to five year averages: – 48 NMEs and original BLAs (14% increase) – 106 non-NME NDAs (28% increase) – 231 efficacy supplements (43% increase)
This information is accurate as of November 30th, 2017. In rare instances, it may be necessary for FDA to change a drug’s new molecular entity (NME) designation or the status of its application as a new biologics license application (BLA). This note applies to all references to NME/Original BLAs in this presentation.
*
6 •6
New Drug Activity in 2017
CDER NME NDAs/BLAs† Filings and Approvals by CY as of 11/30/17 60 50 43
26
23
35
20
33
28
24 25
15
15 11
12
2
12
7
2017*
3
6
2016
2
6
2015
4
6
2014
2
6
2009
5
30
16
2008
6
21
2007
6
18
2006
5
18
2005
2
15
2004
1998
2
11
2003
5
2000
5
1997
2
6
1996
2
1
1995
19
19
2002
25
43
33
31
33
2001
28
1994
0
25
36
36
43
41
2013
34 23
34
22
20 10
26
26
47
26
35
41
32
30
1999
30
38
36 28
41
2012
40
1993
Filings/ Approvals
41
2011
45
2010
50
Calendar Year BLA Approvals
NDA Approvals
Filings
† Multiple applications pertaining to a single new molecular/biologic entity are only counted once. Original BLAs that do not contain a new active ingredient are excluded. * This information is accurate as of November 30th , 2017. In rare instances, it may be necessary for FDA to change a drug’s new molecular entity (NME) designation or the status of its application as a new biologics license application (BLA). This note applies to all references to NME/Original BLAs in this presentation. Since applications are received and filed throughout a calendar year, the filed applications in a given calendar year do not necessarily correspond to an approval in the same calendar year. Certain applications are within their 60-day filing review period and may not be filed upon completion of the review.
7 •7
New Drug Activity in 2017
NME Actions and Approvals by CY 100%
100 82%
90%
0%
Calendar Year
Approval
Non-Approval
2017*
0
2016
10% 2015
10 2014
20%
2013
20
2012
30%
2011
30
2010
40%
2009
40
2008
50%
2007
50
2006
60%
2005
60
2004
70%
2003
70
2002
80%
2001
80
2000
# NME Actions
90
Approval Action Rate
*Data as of 11/30/2017 Includes discrete actions on a given date for an active ingredient which, if approved, would constitute a new molecular entity. Actions for original submissions and resubmissions as well as actions for new BLAs are included. Multiple actions which occur on the same date for multiple dosage forms or indications are counted as a single regulatory action.
8
New Drug Activity in 2017
CDER NME NDAs/BLAs† First Action Approval Rate by FY 100% 90% 89%
80% 78%
70%
70%
77%
72%
71%
60% 50%
54%
50%
50%
40% 30% 20%
52%
48% 42%
36%
35%
46%
43%
31%
30% 23%
45%
56%
52%
25%
25%
10% 0%
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Fiscal Year of Receipt Data as of 11/30/2017 † Multiple applications pertaining to a single new molecular/biologic entity (e.g., single ingredient and combinations) are only counted once. Therefore, the numbers represented here for filings are not indicative of workload in the PDUFA V Program. Original BLAs that do not contain a new active ingredient are excluded. Percentages exclude pending applications from the denominator.
9 •9
New Drug Activity in 2017
Approved Orphan Indications for all NDAs and BLAs† by CY 60 56
50 49 48
40 39 33
30 25
20
18
20 14
14
10 11
12
20 16 17
14
15
2017*
2016
2015
2014
2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1988
20 20
6
1992
1987
13 14 13
1991
8
1990
8
11 10
1989
7
1986
4
1985
2
1984
0
3
1983
10
26 26
24
Calendar Year
† Includes
Efficacy Supplements * Data as of 11/30/2017
10
New Drug Activity in 2017
USA Share of New Active Substances Launched on World Market Remains High
Data as of 11/30/2017 Source: Scrip Magazine (1982 - 2006), Pharmaprojects/Citeline Pharma R&D Annual Review (2007 - 2016)
11
New Drug Activity in 2017
Snapshot of CY 2017 NME NDAs/BLAs† Drug Approvals (1/2) Trade Name
Met PDUFA Goal Date*
Approved on First Cycle
First in Class
Approved First in the U.S.
Breakthrough Therapy
Priority Approval
Fast Track
Accelerated Approval
Orphan Drug
QIDP
TRULANCE PARSABIV EMFLAZA SILIQ XERMELO KISQALI XADAGO SYMPROIC BAVENCIO ZEJULA OCREVUS DUPIXENT AUSTEDO
70% of CY 2017 NME NDA/BLA approvals (28/40) designated and reviewed under priority review 17 breakthrough therapies approved, highest annual approval count to date for program 18 fast track designated products approved, also highest number approved in a given year
INGREZZA BRINEURA RYDAPT** TYMLOS ALUNBRIG IMFINZI
Data as of 11/30/2017 † Multiple submissions pertaining to a single new molecular/biologic entity (e.g., single ingredient and combinations) are only counted once. Therefore, the numbers are not indicative of workload in the PDUFA V Program. Original BLAs that do not contain a new active ingredient are excluded. * A PDUFA Goal Date is marked as met if the application is acted on within its first cycle due date. ** RYDAPT was submitted with two indications, of which one of the indications was granted Breakthrough Therapy designation and the other granted Fast Track designation. QIDP - Qualified Infectious Disease Product
12
New Drug Activity in 2017
Snapshot of CY 2017 NME NDAs/BLAs† Drug Approvals (2/2) Trade Name
Met PDUFA Goal Date*
Approved on First Cycle
First in Class
Approved First in the U.S.
Breakthrough Therapy
Priority Approval
Fast Track
Accelerated Approval
Orphan Drug
QIDP
RADICAVA KEVZARA BAXDELA BEVYXXA TREMFYA NERLYNX VOSEVI IDHIFA MAVYRET BESPONSA BENZNIDAZOLE VABOMERE ALIQOPA
Over ⅔ of 2017 NME NDA/BLA approvals used more than one expedited development or review program
SOLOSEC VERZENIO CALQUENCE VYZULTA PREVYMIS FASENRA MEPSEVII HEMLIBRA
Data as of 11/30/2017 † Multiple submissions pertaining to a single new molecular/biologic entity (e.g., single ingredient and combinations) are only counted once. Therefore, the numbers are not indicative of workload in the PDUFA V Program. Original BLAs that do not contain a new active ingredient are excluded. * A PDUFA Goal Date is marked as met if the application is acted on within its first cycle due date. QIDP - Qualified Infectious Disease Product
13
New Drug Activity in 2017
In CY 2017, CDER Continued To Ensure The Efficiency Of First Cycle Review Met PDUFA Goal Date
All of the (100%) NMEs/BLAs approved to date in 2017 met their PDUFA goal dates
100%
Almost nine out of 10 (88%) of the drugs approved to date in 2017 were approved in the first review cycle
Approved on First Cycle
88% 14 •14
New Drug Activity in 2017
Utilization of Expedited Development and Review Programs Remained High in 2017
Priority Review
More than two – thirds (70%) of the drugs approved to date in 2017 were approved under Priority Review About four out of ten (43%) of the drugs approved to date in 2017 received Breakthrough Therapy designation Almost half (45%) of the drugs approved to date in 2017 received Fast Track designation
Breakthrough Therapy
70%
43% Fast Track
45% 15 •15
New Drug Activity in 2017
2017 Continues A Strong Track Record For Drug Innovation About four out of ten (43%) of the drugs approved to date in 2017 are orphan drugs Almost a third (30%) of the drugs approved to date in 2017 are the first in their class Over three – quarters (78%) of the drugs approved to date in 2017 were first approved in the U.S.
First in Class
30%
Orphan Drugs
43%
Approved First in the United States
78% 16 •16
Development Phase Work
Development Phase Work Continued to Grow in 2017 Commercial INDs With Activity 7000 6000 5000 4000
588
586
695
672
713
2000
3773
4023
4281
4516
2004
2005
2006
2007
2008
1480
1662
824
879
1218
5067
5278
5258
5186
5412
5261
5358
2011
2012
2013
2014
2015
2016
2017
726
732
808
5002
5026
2009
2010
3000 4808
1367
1000 0
Academic Year
Drug INDs
Biologic INDs
Data are from the PDUFA Workload Adjuster and represent a 12 month period of July 1st - June 30th
17 •17
Development Phase Work
CDER Breakthrough Therapy Requests by Division 4%
1% 1% 2% 1%
Oncology Hematology
4%
25%
Neurology
4%
Antiviral Pulmonary / Allergy / Rheumatology Psychiatry
5%
Gastroenterology / Inborn Errors Cardiovascular / Renal
5%
Transplant / Ophthalmology Dermatology / Dental 6% 16%
Anesthesia / Analgesia / Addiction Anti-Infective Bone / Reproductive / Urologic
8%
Metabolic / Endocrinology 8%
10%
Data as of 11/30/2017
18 18
Development Phase Work
CDER Has Granted 192 Breakthrough Therapy Designations Since Inception Oncology
5% 3%
12%
2%
2% 2%
1% 1%
Hematology
29%
3%
Pulmonary / Allergy / Rheumatology
4%
36%
Psychiatry
5%
529 Requests
Antiviral
Gastroenterology / Inborn Errors
192 Granted
6%
Dermatology / Dental Anti-Infective Neurology Anesthesia / Analgesia / Addiction
8% 47%
Transplant / Ophthalmology
12%
22%
Cardiovascular / Renal Metabolic / Endocrinology
Granted
Denied
Withdrawn
Pending
Bone / Reproductive / Urologic
Data as of 11/30/2017
19 19
Development Phase Work
CDER Number of Breakthrough-Designated Development Programs Continues to Grow 90 80 70
Review Phase
60 50
IND Phase
40 30 20
IND Phase
1-Oct-17
1-Aug-17
1-Jun-17
1-Apr-17
1-Feb-17
1-Dec-16
1-Oct-16
1-Aug-16
1-Jun-16
1-Apr-16
1-Feb-16
1-Dec-15
1-Oct-15
1-Aug-15
1-Jun-15
1-Apr-15
1-Feb-15
1-Dec-14
1-Oct-14
1-Aug-14
1-Jun-14
1-Apr-14
1-Feb-14
1-Dec-13
1-Oct-13
1-Aug-13
1-Jun-13
1-Apr-13
0
1-Feb-13
10
1-Dec-12
Total Number of Breakthrough-designated Products in Active Development
100
Review Phase
* Data as of 11/30/17 .Figures includes total # of granted breakthrough designations for drug/indications under active IND development but have not yet received marketing approval or rescission decision. 20
Development Phase Work
CDER PDUFA Formal Meeting Requests by FY 3500 3000
3059 2732
2500 2236
2000 1500
2256
2209
2015
2027
1969
2008
2010
2073
2008
2009
2010
2011
2012
2221
2885
2360
1464
1000 500 0
2003
2004
2005
2006
2007
2013
2014
2015
2016
2017
Fiscal Year
Data as of 9/30/2017 BLAs were transferred to CDER in FY2004
21 •21
Development Phase Work
Meeting Management Changes in PDUFA VI
End-of-Phase 2* meetings are now in a new category, Type B (EOP) meetings with unique parameters – Earlier notification that meeting is granted – Earlier submission of background package – FDA commits to send preliminary comments – Industry commits to respond to prelim comments – 70-day scheduling goal
Type C meetings also changed – Earlier submission of background package – FDA commits to send preliminary comments – Industry commits to respond to prelim comments
Written Response Only meetings: Sponsors may request this option for any meeting category
* Certain EOP1 meetings (e.g., 21 CFR Part 312 Subpart E or 21 CFR Part 314 Subpart H) are also included in this category
22
Development Phase Work
New Meeting in PDUFA VI: Early Consultations on New Surrogate Endpoints
Early consultation can be important when a sponsor intends to use a biomarker as a new surrogate endpoint Consultation is intended to discuss feasibility of the surrogate as a primary endpoint, any knowledge gaps, and how these gaps should be addressed Consultations will be a Type C meeting with the following modifications: – Meeting background package is due at time of request and must include preliminary human data indicating the impact of drug on biomarker – Meeting preparation will involve CDER’s Medical Policy Council – Meetings will be F2F; they will not be converted to a Written Response Only meeting 23
Looking ahead to 2018
Ensure that recruitment and hiring of new drugs program staff continues to be a priority – 1108 FTEs on-board January 1, 2017 – 1198 FTEs projected to be on-board by December 31, 2017 – Net addition of 90 FTEs in 2017
Continued implementation of new PDUFA VI and BsUFA II agreements, other aspects of FDARA and 21st Century Cures Continued ongoing critical evaluation of new drug regulatory program operations to ensure that we can meet program demands and our public health obligations to the American people
24