cder new drugs program 2017 update - food … new drugs program: 2017 update patrick frey chief of...

CDER New Drugs Program:2017 Update

Patrick FreyChief of Staff

Office of New Drugs, CDER/FDA

FDA/CMS SummitDecember 5th, 2017

2

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

Introduction

3

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

Introduction

4

CDER New Molecular Entity Approval Rates by PDUFA Cohort

* 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

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

6 12 18 24 30 36 42 48 54

% N

MEs

Rec

eivin

g App

rova

l

Elapsed Time (months)

Pre-PDUFA (1988-1992) PDUFA I-III PDUFA IV PDUFA V (receipts through 3/31/2016)

Pre-PDUFA

PDUFA I-III

PDUFA IV

PDUFA V

New Drug Review Process Efficiency

5

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., mid-cycle 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

New Drug Review Process Efficiency

6

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)

•6

* 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.


7

† 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.

CDER NME NDAs/BLAs†

Filings and Approvals by CY as of 11/30/17

•7

2 2 1 6 5 5 2 2 5 6 6 5 2 4 2 3 6 6 6 62

11 127

12

2319

28

47

34

25 3325 19

1115

31

1818

1621

2015

24

33

25

3033

15

28

2826

50

4541

43

36

2630

2226

32

38

26

35 3436

23

41 41

36

41

35

43 43

0

10

20

30

40

50

60

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

*

BLA Approvals NDA Approvals Filings

Calendar Year

Filin

gs/

Appr

oval

sNew Drug Activity in 2017

8

*Data as of 11/30/2017Includes 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.

NME Actions and Approvals by CY

82%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0

10

20

30

40

50

60

70

80

90

100

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

*

# NM

E Act

ions

Approval Non-Approval Approval Action Rate

Calendar Year


9

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.

CDER NME NDAs/BLAs†

First Action Approval Rate by FY

•9

36%

23%

30%

50%

35%

25%

54%

31%

25%

50% 48%

42%45%

52% 52%

46%43%

56%

70%72%

78%

89%

77%

71%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

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


10

Approved Orphan Indications for all NDAs and BLAs† by CY

† Includes Efficacy Supplements* Data as of 11/30/2017

2 3 47 8 8

11 1013 14 13

10 11

25

1820 20

14

6

1412

14

20

24

16 1720

15

26 26

33

49 48

39

56

0

10

20

30

40

50

60

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

*


Calendar Year

11

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)


12

Snapshot of CY 2017NME NDAs/BLAs† Drug Approvals (1/2)

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

Trade NameMet PDUFA Goal

Date*Approved on First

Cycle First in ClassApproved 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

INGREZZA

BRINEURA

RYDAPT**

TYMLOS

ALUNBRIG

IMFINZI


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

13

Trade NameMet PDUFA Goal

Date*Approved on First

Cycle First in ClassApproved First in the

U.S.Breakthrough

Therapy Priority Approval Fast TrackAccelerated

Approval Orphan Drug QIDP

RADICAVA

KEVZARA

BAXDELA

BEVYXXA

TREMFYA

NERLYNX

VOSEVI

IDHIFA

MAVYRET

BESPONSA

BENZNIDAZOLE

VABOMERE

ALIQOPA

SOLOSEC

VERZENIO

CALQUENCE

VYZULTA

PREVYMIS

FASENRA

MEPSEVII

HEMLIBRA

Snapshot of CY 2017NME NDAs/BLAs† Drug Approvals (2/2)

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


Over ⅔ of 2017 NME NDA/BLA approvals used more than one expedited

development or review program

14

In CY 2017, CDER Continued To Ensure The Efficiency Of First Cycle Review

All of the (100%) NMEs/BLAs approved to date in 2017 met their PDUFA goal dates

Almost nine out of 10 (88%) of the drugs approved to date in 2017 were approved in the first review cycle

•14


Met PDUFA Goal Date

100%

Approved on First Cycle

88%

15

Utilization of Expedited Development and Review Programs Remained High in 2017

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

•15


Priority Review

70%Breakthrough Therapy

43%Fast Track

45%

16

2017 Continues A Strong Track Record For Drug Innovation

•16

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.


Orphan Drugs

43%

Approved First in the United States

78%

First in Class

30%

17

Development Phase Work Continued to Grow in 2017

•17

Data are from the PDUFA Workload Adjuster and represent a 12 month period of July 1st - June 30th

3773 4023 4281 4516 4808 5002 5026 5067 5278 5258 5186 5412 5261 5358

588586

695672

713726 732 808

824 879 12181367 1480 1662

0

1000

2000

3000

4000

5000

6000

7000

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Drug INDs Biologic INDsAcademic Year

Commercial INDs With Activity

Development Phase Work

18

CDER Breakthrough Therapy Requests by Division

18

Data as of 11/30/2017

25%

16%

10%8%

8%

6%

5%

5%

4%

4%

4%2% 1% 1% 1%

Oncology

Hematology

Neurology

Antiviral

Pulmonary / Allergy /RheumatologyPsychiatry

Gastroenterology / Inborn Errors

Cardiovascular / Renal

Transplant / Ophthalmology

Dermatology / Dental

Anesthesia / Analgesia /AddictionAnti-Infective

Bone / Reproductive / Urologic

Metabolic / Endocrinology


19

CDER Has Granted 192 Breakthrough Therapy Designations Since Inception

19

Data as of 11/30/2017

36%

47%

12%

5%

Granted Denied Withdrawn Pending

29%

22%12%

8%

6%

5%

4%

3%3%

2%2% 2% 1% 1%

Oncology

Hematology

Antiviral

Pulmonary / Allergy / Rheumatology

Psychiatry

Gastroenterology / Inborn Errors

Dermatology / Dental

Anti-Infective

Neurology

Anesthesia / Analgesia / Addiction

Transplant / Ophthalmology

Cardiovascular / Renal

Metabolic / Endocrinology

Bone / Reproductive / Urologic

192 Granted

529 Requests


20

CDER Number of Breakthrough-Designated Development Programs Continues to Grow

* 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.

IND Phase

Review Phase

0

10

20

30

40

50

60

70

80

90

100

1-De

c-12

1-Fe

b-13

1-Ap

r-13

1-Ju

n-13

1-Au

g-13

1-Oc

t-13

1-De

c-13

1-Fe

b-14

1-Ap

r-14

1-Ju

n-14

1-Au

g-14

1-Oc

t-14

1-De

c-14

1-Fe

b-15

1-Ap

r-15

1-Ju

n-15

1-Au

g-15

1-Oc

t-15

1-De

c-15

1-Fe

b-16

1-Ap

r-16

1-Ju

n-16

1-Au

g-16

1-Oc

t-16

1-De

c-16

1-Fe

b-17

1-Ap

r-17

1-Ju

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tal N

umbe

r of B

reak

thro

ugh-

desig

nate

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duct

s in

Activ

e Dev

elop

men

t

IND Phase Review Phase


21

CDER PDUFA Formal Meeting Requests by FY

•21

Data as of 9/30/2017BLAs were transferred to CDER in FY2004

1464

2015

2236 2256 22092027 1969 2008 2010 2073

22212360

27322885

3059

0

500

1000

1500

2000

2500

3000

3500

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017


Fiscal Year

22

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 anymeeting 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

23

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


24

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

cder new drugs program 2017 update - food … new drugs program: 2017 update patrick frey chief of...

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