Download here - Portland Actuarial Club

Medical Genetics
and
Orphan Drugs
Csaba Mera, MD
Medical Director, ODS
Portland Actuarial Club
November 17, 2009
Broadway Room, Heathman Hotel
EXPERIMENTS IN PLANT HYBRIDIZATION (1865)
1822-1884
Mendel, Gregor. Versuche über Plflanzenhybriden. Verhandlungen des naturforschenden Vereines in
Brünn, Bd. IV für das Jahr 1865, Abhandlungen, 3–47.
"We have found the secret of Life."
James D. Watson and Francis Crick propose the double helix structure of DNA – 1953
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Victor McKusick
Founding father of medical genetics
First medical genetics program
Johns Hopkins 1957
Early advocate of mapping the human
genome
Lasker Award for Special Achievement
in Medical Science 1997
February 2001 - joint publications
Improved drafts in 2003 and 2005
Human genome ~ 24,000 genes
All human races are 99.99 % alike,
Genetic archaeology – new understanding
Changes in the Foxp2 gene during
the course of evolution resulted in
the development of language in humans
It took
6 million years
but now I can
really SPEAK!!
6 M yrs – Two fixed amino acid changes
130 M yrs
One amino acid change
The Journey of Man
Dr. Spencer Wells – National Geographic Explorer-in-Residence
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Compendium of human genes and genetic phenotypes
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Comprehensive, authoritative, timely (updated daily)
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Links to other genetics resources
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The full-text, referenced overviews on all known mendelian
disorders and over 12,000 genes
http://www.ncbi.nlm.nih.gov/omim/
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BRCA1 and BRCA2
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About 10% of breast cancer patients
~ 20,000 cases
$2,000 per test
$40, 000,000 annually
HNPCC
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About 5% of colon cancer patients
~7,000 cases
$2,000 per test
$14,000,000 annually
Lawrence WF, et al. Cost of Genetic Counseling and Testing for BRCA1 and BRCA2 Breast Cancer
Susceptibility Mutations1Vol. 10, 475–481, May 2001 Cancer Epidemiology, Biomarkers & Prevention
Relationship testing
• Chain of custody
• In home
• $200 - $500
Disease prediction
• Genomewide association study
• Not ready for prime time
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Genentech 1978
recombinant DNA to
induce E. coli to produce
human insulin 1978
Growth hormone
Blood clotting factors for
hemophilia
Gonadotropins
Hepatitis B vaccine
>350 drugs being tested
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Characteristics that differentiate specialty drugs
from traditional drugs include
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Recombinant DNA technology or other biological process
Target diseases with no currently available treatments
Injection or infusion*
Complex handling requirements
Requires close monitoring and support
Patient education and coordination of care needed
Higher risk of severe side effects
High cost (CMS = $600 or more per patient per month)
*Although, fastest growing route of administration is oral
Adapted from EMD Serono Injectables Digest 5thEdition
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The Orphan Drug Act (ODA) of January 1983
Lobbying from the National Organization for Rare Disorders
Encourages pharmaceutical companies to develop drugs for
diseases that have a small market through:
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Tax incentives
Enhanced patent protection and marketing rights
Modified clinical testing requirement
Clinical research financial subsidization
Creating a government-run enterprise to engage in research and
development
Drug
Disease
Disease
Prevalence
Cost/30 days
Cinryze
C1 inhibitor
20,000
$45,000
Fabrazyme
Fabry disease
2,600
$11,250
Stelara
Psoriasis
500,000
$11,200
Nplate
Chronic ITP
3,000
$9,000
Avastin
Advanced breast
cancer
40,000
$8,000
Afinitor
Advanced renal
cancer
13,000
$6,000
Temodar
Advanced brain
10,000
$3,200
Cinryze (C1 INHIBITOR, HUMAN)
$45,000 / 30 day supply
cancer
Nplate (ROMIPLOSTIM)
$9,000 / 30 day supply
Annual
Promacta (ELTROMBOPAG)
588,600
$6,986,250,000
$3,300 / 30 day supply
A leading cause of blindness
Prevalence of AMD
1.75 million in 2009 (3 million by 2020)
Ranibizumab
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Recombinant monoclonal antibody
Binds to and inhibits all the biologically
active forms of vascular endothelial
growth factor A
Monthly vitreous injection monthly
Duration of treatment - indefinitely
Prevents vision loss, improves visual acuity
Cost - $1,950 per dose
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1.75M x $1,950 = $41 Billion annually
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Steinbrook R. The Price of Sight — Ranibizumab, Bevacizumab, and the Treatment of Macular Degeneration. NEJM 2006; 355:1409-1412
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Epidermal growth factor receptor (EGFR) transmits signals through a set
of intracellular proteins, which instruct cancer cells to reproduce and
metastasize.
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Blocking EGFR stops this malignant signaling.
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Two chemotherapy drugs: Erbitux and Vectibix
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However, in patients with mutant V-Ki-ras2 Kirsten rat sarcoma viral
oncogene homolog (KRAS), the signaling continues despite EGFR
therapy.
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Mutated KRAS genes have been detected in about 40% of metastatic
colorectal cancer patients, depending on the testing used.
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28,274 patients annually
Van Cutsem et al J Clin Oncol 2007; 25[18S]:4000)
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Cost of KRAS testing at a commercial laboratory: $452/test
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Average wholesale price of Erbitux
 loading dose of 400 mg/m2 = $3,986/dose
 weekly dose of 250 mg/m2 = $2491/dose
 Mean number of Erbitux infusions: 24
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Drug cost per patient = $61,279
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Median survival
 BSC
4.6 months
 BSC+Erbitux 6.1 months
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Testing and treatment cost for all patients $630 Million
Van Cutsem et al J Clin Oncol 2007; 25[18S]:4000)
BSC + Vectibix vs. BSC alone
Jonker DJ, et al. New England Journal of Medicine, November 15, 2007.
Is it worth it?
NAME
Jason Alexander
Woody Allen
Mario Andretti
Sean Astin
Ludwig Van Beethoven
David Ben-Gurion
Robert Blake
Humphrey Bogart
Napoleon Bonaparte
Bono
Matthew Broderick
Mel Brooks
Gary Burghoff
Richard Burton
James Cagney
Truman Capote
Andrew Carnegie
Gary Coleman
Phil Collins
Lou Costello
Tom Cruise
Billy Crystal
Salvador Dali
Sammy Davis Jr.
Danny DeVito
Robert Downey Jr.
HEIGHT
5'5"
5'6"
5' 7½"
5'6"
5' 3¾"
5'0"
5'4"
5'8"
5'6"
5'7"
5'8"
5'4"
5' 5"
5'8"
5'7"
5'4"
5'0"
4'8"
5' 6"
5' 5"
5'8"
5'8"
5'7"
5'3"
5'0"
5'7"
NAME
AREA
Entertainment
Entertainment
Sports
Entertainment
Music
Politics
Entertainment
Entertainment
Politics
Entertainment
Entertainment
Entertainment
Entertainment
Entertainment
Entertainment
Literature
Entrepreneur
Entertainment
Entertainment
Entertainment
Entertainment
Entertainment
Art
Entertainment
Entertainment
Entertainment
5'6"
Entertainment
Emilio Estevez
5'7"
Entertainment
Peter Falk
5'6"
Entertainment
William Faulkner
5'6"
Literature
F. Scott Fitzgerald
5'7"
Literature
Michael J. Fox
5'4"
Entertainment
Buckminster Fuller
5'2"
Scientist
Ghandi
5'3"
Politics
Paul Giamatti
5'7"
Entertainment
Maurice & Robin Gibb (Bee Gees)
5'8"
Entertainment
Joel Grey
5'5"
Entertainment
Gus Grissom
5' 5" Astronaut
Scott Hamilton
5'4"
Sports
Armand Hammer
5'5"
Entrepreneur
Alfred Hitchcock
5'6"
Entertainment
Dustin Hoffman
5'6"
Entertainment
Anthony Hopkins
5'8"
Entertainment
Bob Hoskins
Andrew Carnegie 5’ 0”
HEIGHT AREA
Bob Dylan
5' 5½" Entertainment
Harry Houdini
5'5"
Curly Howard
5' 5" Entertainment
Entertainment
Moe Howard
5'4"
Entertainment
Elton John
5'4"
Entertainment
Davy Jones
5'3"
Entertainment
John Keats
5'1"
Literature
Ben Kingsley
5'8"
Entertainment
Nikita Khrushchev
5'3"
Politics
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Targeted drug therapy
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Genetic profiling
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Gene therapy
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Genetic manipulation
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Expenditures will grow >15% compared to
<5% for conventional drugs
Specialty drugs are >50% of those in
Phase III development
Oral therapies may augment or replace
existing injected or infused agents.
Atheer Kaddis, PharmD and Debbie Stern, RPh
Academy of Managed Care Pharmacy - Fall Educational Conference - October 9, 2009