505(b)(2) Why Now?

505(b)(2) Why Now?

Ken Phelps

President & CEO, Camargo Pharmaceutical Services, LLC

Gemma Casadevall, PhD.

Chief Scientific Officer, Medichem, S.A.

http://www.reuters.com/article/us-pharmaceuticals-approvals-idUSKBN14M08R

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

505(b)(2) NDAs Approved

Camargo Database

$ in billions

The Patent / Generics Cliff (Value of product at risk 2004-2020)

Generic – New Business Strategy

Generic

• Same Drug Product

• Substitution @ Pharmacy

• Well-established: • Development requirements

• Cost

• Profits

• Competition

New Drug

• What Product?

• How to sell?

• Unfamiliar: • Development requirements

• Cost

• Profits

• Competition

The road to regulatory approval is just one piece of the puzzle.

Strategic Drug Development

Regulatory Can we convince the agency on what program is necessary? Creative and optimal?

Your path

What is public? Your development program

FDA Requirements for

NDA Approval

8

05(b)(2) Process

FDA

OK? Start Feasibility Pre-IND

Stop

Pre-IND Meeting @ FDA

• Meeting Request

• Submission Package

• FDA Preliminary Response

• Pre-IND Meeting

• On-Site

• Written Response Only (WRO)

• Telephonic

• FDA Final Meeting Minutes

505(b)(2) and the Importance of the Pre-IND Meeting

9

Pre-IND NDA

Maintain the Link

Exclusivity

505(b)(2) Products without 3-Year Exclusivity

that Experienced Generic Competition within the first 3 years

505(b)(2) Products without 3-Year Exclusivity

that Experienced Additional Generic Competition after 3 years

http://camargopharma.com/2016/01/3-year-exclusivity-may-not-be-worth-as-much-as-you-think/

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505(b)(2) Process

FDA

OK? Start ND

A S

ub

missio

n

Clinical Trial Materials

Analytical Methods

Preclinical

Regulatory Process

Medical Communications

Feasibility Pre-IND Phase 3 Form

ula

tion

Phase 2 Phase 1

Stop




Scientific Can it be done? Reliably and consistently manufactured?

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Probability of Success by Stage

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Phase 1 to 2 Phase 2 to 3 Phase 3 to NDA Filing NDA Approval Phase 1 to NDA

Approval

New Molecular Entity 505(b)(2)

Source: Clinical Development Success Rates 2006 – 2015. A report by BIO (Biotechnology Innovation Organization),

Biomedtracker, and Amplion. 2016




Medical Does the product satisfy an unmet need? Do we understand the practice of medicine?


Drug for Which Patient?

Limits of Patient Response

~70% of pediatric Rx are off-label

GAO, Pediatric Drug Research, May 2001; GAO-01-705T.

Target Product Profile



Commercial

Is the product commercially viable? How will it be reimbursed?


Medical Does the product satisfy an unmet need? Do we understand the practice of medicine?


Launch-Aligned Monthly TRx’s Recent AED Launches

ADHD Market – 505(b)(2) Product Launches

Product Selection

Gemma Casadevall, PhD.

CSO

Medichem

Hands on the project Case study

Strategic Development…opportunities or challenges?

Strength Dosage form

Dosing regimen Combination product

Formulation

Active ingredient

Bioinequivalence

Route of administration Rx/OTC switch

Indication

The selection process

Task

Product Selection Criteria

questionnaire

Medichem-specific process filters

List of top 10 APIs

Prioritization of top 10 APIs

Filtering steps to top 4 APIs

Prioritizing of top 4 APIs

Agreement on top 2 APIs

Identification of top API

API Synthesis

(Enantiomers/

Salts) Formulation Development Options

Potential Combination

Options

2 possible

different salts

identified

1. Powder/Oral Suspension

Currently product an XR do ot c ush o che fo ulatio

Pediatric dosing provided in labeling did not meet

primary endpoint.

Doses above X mg/kg qd have not been studied.

2. Lower strength

recommended starting dose not amongst the

approved strength

3. Higher strength

Dosages above Y mg per day have not been studied.

4 possible fixed dose

combinations identified

PRODUCT

API

Specialty APIs

Enhanced APIs

Multiparticulates

Minitabs

ODT

FDF

Value added medicines

Oral Sol/Susp.

Smart Polymers

Long-acting injectables

Specialty FDFs New opportunities

Current business

TECHNOLOGY PLATFORMS

Focus on what you can do…

and what is feasible

Action Plan

Focus on specific technologies with defined timelines to obtain

Value Added Products

Available resources + investments

Markets / competition Technologies

The Need:

The Challenge:

The added value:

0

20

40

60

80

100

0 10 20 30 40

Dis

solv

ed

dru

g (

%)

Time (h)

RLD

PRODUCT

API

Specialty APIs

Enhanced APIs

Multiparticulates

Minitabs

ODT

FDF


Oral Sol/Susp.

Smart Polymers



Current business




Source. Camargo Blog Jan 2017

PRODUCT

API

Specialty APIs

Enhanced APIs

Multiparticulates

Minitabs

ODT

FDF


Oral Sol/Susp.

Smart Polymers



Current business




60,8%

11,1%

3,9%

15,0%

2,6%

1,3% 0,7%

2,0%

2,6% Oral Topical

Inhalation Injection + IV

Ophtalmic Rectal

Otic Transdermal

Nasal

36,6%

22,6%

12,9%

20,4%

7,5%

Tablet

Capsule

ODT

Oral Liquid

Others

Source. Camargo Blog Jan 2017

Improving administration and ease of use for subpatient groups

SPRINKLE MULTIPARTICULATE DDS

ORAL MULTIPARTICULATE XR SUSPENSIONS

ODT/MUPS

Multiparticulate Drug Delivery Systems (MDDS) advantages

• MDDS offer a high degree of flexibility in the design: capsules, tablets (microspheres, coated

beads), sachets, suspensions...

• They can be divided into desired dose strengths without formulation or process changes and/or

also can be blended to deliver incompatible active agents simultaneously and/or to provide

different release profiles at the same or different sites in the gastrointestinal (GI) tract.

• They offer a wide range of drug release profile flexibility for single or multiple drug combinations

• MDDS disperse freely in the GI tract, maximize drug absorption, minimize local irritation of the

mucosa by certain irritant drugs, and reduce inter- and intrapatient variability.

• Provide predictable and consistent gastrointestinal transit and lower chances of undesirable events

(e.g., dose dumping, colonic streaming) associated with tablets.

Qualitative assesment

Feasibility report Quantitative Assesment

Key points: Biz Case, do your homework!

• Market and Opinion Leader Assessment

• Portfolio balance

• Timing

• Short or long term

• Resources/ Investments

• Capability / API

• Market: US, EU, Regional

The internal analysis: Platform vs. Protection

PLATFORM APPLICATION/ TYPE OF

PRODUCT

MARKET PROTECTION

ORAL MDDS Pediatrics Prior art

ORAL MDDS Geriatrics May be product specific +device

ORAL MDDS HPAPI May be product specific

INJECTABLES IR Prior art

INJECTABLES

XR May be product specific

INJECTABLES

Smart polymers Blue ocean If we have a new polymer

A clear regulatory pathway in the US vs EU

Will the product be able to sell in both markets? A case by case story

Will the product be able to sell for geriatric and paediatric patients?

Target Product Profile

Description Product X, for oral administration, available as extended-release MDDS (sachet, capsule,...) Product X has been formulated to provide a controlled and predictable release of the drug for once-daily administration. Product X capsules contain specially loaded multipaticulates equivalent to X mg of drug.

Indication and Usage

Product X is indicated for the treatment of: • Indication 1 • Indication 2 • Indication 3

Dosage • Administer once daily. Dosing of Product X should be individualized. • Indication 1: Recommended starting dose is X mg or double, with the highest dose tolerated up to 6 x X mg. • Switching from immediate-release to Product X: use the same total daily dose of Product X.

Dosage Form and Strength Product X Extended-Release MDDS: x mg

Administration

Product X Capsules: • May be swallowed whole. • Contents may be mixed in liquid of choice and consumed immediately. • Contents may be sprinkled on soft food. The drug/food mixture should be swallowed immediately. • Contents may be administered through a nasogastric tube.

Product X Sachets: • Contents may be mixed in liquid of choice and consumed immediately. • Contents may be sprinkled on soft food. The drug/food mixture should be swallowed immediately. • Contents may be administered through a nasogastric tube.

Product X X mg

Example of a Sachet (not actual Product X)

Road towards success:

10 m 1 m 1 m 6-9 m

New candidates proposal

PK Studies

CMO

CRO

A platform enabler process:

MPDDS

Technology Available

Target Population

Geriatrics

Pediatrics

General (when only tablet

available)

Advantages

Can be mixed with semi-

solid food

No risk of aspiration

Challenges Low appetite

Techical difficulties

Available drugs Low

Commercial Price TBD

Profitability High

Buy or develop

Buy or develop

Conclusions

• 505(b)(2) pathway is a clear regulatory way to promote innovation with moderate investment vs. NCE

• Most of the products offer a lower-risk market entry point

• 505(b)(2) de elop e t oppo tu ities face u i ue challe ges scie tific, egulato y, fi a cial… , thus:

If we want this investment to be worth we should pay careful attention to:

Listen to current patient/market/kol needs

Focus on own capabilities Resources/ Investments/technology

Keep up ith the Age cy’s cu e t thi ki g

Face it:… e li e i a co sta t cha gi g egulato y e i o e t

Summary

With 505(b)(2), an experienced partner enables developing and delivering a faster, lower cost, and lower risk program.

For weekly drug development insights, subscribe to the Camargo 505(b)(2) blog at:

CamargoPharma.com/contact-us/

For more about Medichem, visit

Medichem.es/contact/

Thanks for your attention

Documents

505(b)(2) Why Now?