Leah M Hamburg

Public Health 2008

Introduction
 Orphan (Rare)Disease:
 A disease which affects less than 200,000 individuals in
the US.
 Prevalence < 5:10,000
 > 5,000 diseases meet criteria
 Combined, up to 25 million people in North America.

Brugada Syndrome Marfan’s Syndrome

Tetrology of Fallot Guillan-Barre Syndrome
Genetic Autism ALS
Multiple Myeloma Scleroderma
Polycythemia Vera Alpha-1 antitrypsin deficiency
Snake Envenomation Cystic Fibrosis
Orphan Drug Act of 1983
I. 7-year marketing exclusivity. (renewable)
a. Drugs do NOT have to be patented. FDA agrees to take
over regulation.
II. 50% Tax break during human clinical trials.
III. Grants to subsidize orphan drug development.
IV. Specialized protocols for clinical trials designed by
the FDA.
a. Same standards of efficacy and safety
b. Patients w/ dz can be enrolled earlier
c. Smaller #’s of patients required. (more rigorous)
Why was ODA neccessary?
 Economically not feasible
 Approx $93 million per successful drug
 Difficulties reaching appropriate patient populations
 No one was tracking rare diseases.
 #’s not sufficient to meet FDA clinical trial
requirements.
 Trials discontinued because of drug failure w/
common diseases
The story of Adagen
 Drug to treat SCID
 ODA Designation in 1984.
 8pts in clinical trail, control group
was historical.
 Only 14 pts in country affected by
SCID at time of trial.
 100% efficacy.
 Proven safe – no adverse events in 14
years of drug use.
 Approx $100,000 annually for
treatment.
Post-ODA Era
 1973-1983, only 10 drugs
developed for orphan
diseases.
 1983-2003, 200 drugs
released, 800 more in
development.
 5/16/2008, 325 orphan
drugs on the market.
Orphans you may know
 Gleevac  Rituximab
 CroFab  All replacement
 Digibind Coagulation factors.
 Epogen  Diazepam (Rectal)
 Infliximab
 N-acetylcystiene (NAC)
 Humira
 Proleukin
 Botox
Pricing
“Regular” drugs
 2:1 $ spent on consumer
marketing vs. drug reps
 R&D funding from numerous
public and private sources.
Private investors expect
returns.
 10-20 yrs to get a patent
Orphan Drugs
 Consumer marketing is not
cost effective – too few
patients.
 Large government grants for
R&D.
 50% tax break for clinical
trials
 No patent required, 7yr
monopoly.
Some Numbers
 Imiglucerase -- Gaucher’s Disease.
 $400,000/year
 2004, Genzyme made $800 million on Imiglucerase.
 Neutropin – GH Deficiency
 On market since 1985.
 approx $100,000/yr (30kg child)
 2004, Genentech made $354 million on Neutropin.
 Thalidomide – Leprosy and Multiple Myeloma
 Take off market in 1960’s. Orphan drug status in 1998.
 $53/pill in US.
 7¢/pill in Brazil.
How did this happen?
 No price cap written into the
ODA of 1983.
 1990’s: bills to rescind market
protection once profits
exceeded 25%. Passed House
and Senate, vetoed by Bush.
 Patients don’t have any other
options.
 Few or No duplicate drugs
 Decreased bargaining power
for drug prices.
We love it!
 Let it be because…
 Over 12 million patients helped.
 “blockbuster” orphans are the exceptions to the rule.
 Attempts to curb prices would dissuade new drug
development.
 Expand the ODA to include…
 Tax cuts for the non-clinical phases of R&D.
 Expand protection to investigation of Neglected
Diseases.
 It is possible to get the drugs for free, so exorbitant
costs are not a problem.
This isn’t what we expected.
 This is a critical piece of legislation, however, it has
gotten out of control.
 Placing a ceiling on profits.
 Marketing restrictions…
 Allowing shared market exclusivity upon approval by
the FDA.
 No more market exclusivity if patient population grows
to >200,000.
 Restrict marketing protection to a specific aspect of the
drug – would allow for “sister drugs.”
 Refundable tax credit instead of tax break.
Bibliography
 Anand, G. How Drugs for Rare Diseases Became Lifeline for Companies. The
Wall Street Journal, Nov 15, 2005. Accessed online 10/31/08.
 Haffner ME. Adopting Orphan Drugs – Two Dozen Years of Treating Rare
Diseases. N Eng J Med, Feb 2006, 354(5):445-447.
 Haffner ME, Torrent-Farnell J, Maher PD. Does orphan drug legislation really
answer the needs of patients? Lancet, June 2008, 371(9629):2041-4.
 Reaves ND. A model of effective health policy: the 1983 Orphan Drug Act. J
Health Soc Policy. 2003; 17(4): 61-71.
 Schieppati A, Henter J-I, Aperia A. Why rare diseases are an important medical
and social issue. Lancet, June 2008, 371(9629): 2039-2041.
 Villarreal MA. Orphan Drug Act: background and proposed legislation in the
107th congress. CRS report for congress. July 25, 2001, code RS20971. Accessed
online 11/4/08.
 Wastfelt M, Fadeel B, Henter J-I. A journey of hope: lessons learned from
studies on rare diseases and orphan drugs. J Intern Med, Jul 2006: 260(1): 1-10.
 FDA website. List of Orphan Designations and Approvals.
http://www.fda.gov/orphan/designat/ list.htm
 FDA website. The Orphan Drug Act. http://www.fda.gov/orphan/oda.htm