Orphan Drugs – 2011 What’s Happening?

Haffner Associates, LLC 1

Orphan Drugs – 2011What’s Happening?

Women in BIO

Marlene E. Haffner, MD, MPH

[email protected] 301 984 5729 - Office 301 641 4268 – cell November 1, 2011


LOTS!


INCENTIVES 7 Years Exclusive Marketing Waiver of PDUFA Filing Fee Assistance of OOPD Tax Credits – 50 % of clinical

development costs – one year fall back; 20 year carry

forward Grant Support Recommendations from Brownback

Brown Report Associate Director for Orphan Drugs

- CDER


Accomplishments ~ 390 products approved > 2000 designations > 15,000,000 patients

potentially treated > 45 products approved

through the grants program


2009 Emergence of Big PhRMA GSK Novartis Pfizer Genentech/Roche Sanofi


Biotech and Orphan Products

Began with Genentech – hGH - and has progressed

Now the emergence of “molecular medicine”

Personalized medicine – genetic knowledge fits well with orphan drug development


1992 Regulations 2011 NPRM 2011 NPRM released week of

October 21st

Codifies practices already in place

Medically plausible subsets vs the disease process

Better defines the designation process


Review and Approval of Orphan

ProductsOrphan Products must be Safe and Effective

for their intended use Is that possible? FDA has demonstrated flexibility 90 of 135 non-oncology approvals approved

with non standard approaches – NORD study Smaller clinical trials Historical controls Single arm/non-randomized Case-by-case


Current Issues and Activities Safety concerns REMS Cost Reimbursement Large # of orphan programs

and activities globally Increasing coordination with

the EU


Safety Orphan Products approved based on small

clinical trials Infrequent adverse events will not be seen Until the last 3 – 4 years “there had been no

safety concerns with orphan products” That has changed – e.g. EPO – 25 years

following initial approval; Botulinum toxin - black box warning

Virtually all new orphan approvals carry a REMS


REMS – Risk Evaluation and Mitigation Strategy Orphan Products with REMS –

Nplate – no safety signals in clinical trials

Botulinum toxin – new findings FDA (and Congress) erring on

the side of safety Allows FDA to approve some

products which would not previously have been approved


Cost of Orphan Drugs US expenditure for drugs - 2.2% of GDP in

2000; will be 5.6% in 2030 Newest products in the health care arena

are Biotech Biotech products are expensive – whether

they are orphan products or not Because of some high profile examples,

orphan products are often sighted as expensive Some orphan products are

expensive; most are not Economies of scale for a small

population is not present – need to explain better to the public


Reimbursement

Must figure reimbursement strategies as drug development proceeds. This involves working with CMS and individual insurance companies

Must explain to patient groups the rationale for cost of the product if high. Cost may by necessity be high

Some EU member states very conservative in reimbursement

Recent unfortunate examples


Personalized Medicine Human genome allows more

targeted therapies Many of these will subdivide

larger diseases into smaller ones which may be orphan diseases – gene mutations

NIH TRND program Repurposing of old drugs


What does this mean for my company? What is your strategy? Orphan Products generally treat life

threatening diseases – may mean faster approval

Common application format in EU and US – saves money

Tax incentives Exclusivity Waiver of PDUFA Filing Fee – $1.8

mil in 2011


Examples of Office of Orphan Products

Assistance


Envenomation Envenomation – OOPD

convinced review division to broaden thinking re indication – approved product in 2011

Other envenomation products being developed


Narcolepsy How should the product be

DEA scheduled? Without the intervention of

OOPD the product may not have been developed


Prevalence and # of clinical trials A disease with < 100 patients

in the US Hard, if not impossible, to do

TWO placebo controlled trials When to use historical controls How to develop phase 1,2,3

trials Inviting the OOPD to meetings

with the division Need for Natural History

studies


Toxicity testing The disease is lethal at a very

young age What are the considerations Can toxicity testing be done

following clinical trials in humans

Need new methodologies for preclinical drug development


Roll of the Associate Director for Orphan Products in CDER Primarily policy/consistency Evaluating new science with

regards to Orphan Product development

Biomarkers Close collaboration with the

OOPD Hopefully will grow in size


A New Day in OOPD Appointment of new Acting

OOPD Director – Gayatri Rao, MD, JD

NPRM issues 19 years following initial regulations

Increasing # of companies join the drive toward rare disease therapies

NIH efforts Commitment of FDA with

Associate Director for Orphan Products


?Marlene E. Haffner, MD, MPH

Haffner Associates, LLC [email protected]

www.mhaffner.com 301-984-5729 301-641 4268

Orphan Drugs – 2011 What’s Happening?

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