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