Personalized Medicine: Are we there yet?

Lecture at Brigham Young UnversityDecember 9, 2014

Reid J. Robison, MD MBA

Right now, we wait for a disease to occur, then we act

The future is predictive, preventive & personalized

Personalized medicine: Are we here yet?

The use of genomic information to identify disease origins, develop targeted therapies, and improve outcomes

Precision Medicine

The Sequencing Explosion

•  Cancer moved from a single disease to hundreds of specific diseases

•  Medicine moves from targeting symptoms to targeting causes

•  Healthcare moved from defining diseases by organ system to defining them by mutations and networks

•  Genome sequencing moves to the clinic

•  Data science is transforming healthcare

What is happening in healthcare?

•  Sensors/trackers/devices

•  Your car has a dashboard, why don’t you?

•  We can do on our cell phone now what we could only dream of years ago

•  Look how fast we have gone from room-sized computers to powerful smart phones. What will healthcare look like in 20 years?

•  Of the 7 billion people on the planet, 6.2 billion have cell phones (and 91% keep them within 3 feet 24 hours a day)

Digital health goes mainstream

•  Digital Health + Proactive patients = Progress towards Predictive, Preventive & Personalized medicine

Progress

•  PAST

•  Doctor-centric

•  Doctor is the CEO of your health

•  One size fits all

•  Pay for costs & procedures

From “patient” to “consumer” From “sickness” to “wellness” based

•  FUTURE

•  Patient-centric

•  Patient is in charge of his/her health

•  Personalized medicine is the norm

•  Pay for outcomes & value

•  More costly than ever to bring a drug to market

•  Pharma is innovating less, buying/licensing instead (universities & small companies)

•  Orphan drug incentives

•  Disease advocacy groups are funding development

Drug development challenges

•  “We are on the tipping point of a whole new game in how we develop drugs.” Janet Woodcock, MD Director, Center for Drug Evaluation and Research, FDA

The Tipping Point

•  >$500 million per year in drug discovery

•  CF Foundation gave $75 million to Vertex

•  Kaleydeco FDA approved in 2012

•  “This is a breakthrough therapy for the cystic fibrosis community because current therapies only treat the symptoms of this genetic disease.” Janet Woodcock, MD Director, Center for Drug Evaluation and Research, FDA

•  Pfizer & CF Foundation in $58 million pact

Venture Philanthropy

•  Genzyme offers refund for treatment failure with kidney cancer drug Mozobil

•  Celgene offers partial refund to non-responders of CML/AML drug Vidaza

•  Breakthrough Hepatitis C treatment (Sovaldi) costs $1000 a pill but is worth it, and payers are paying

•  Can cure up to 90% of patients, with fewer side effects, in a fraction of the time

Early signs of Outcome-based payment

•  50% of cancer drugs approved in 2013 target specific deficits

•  Beyond targeted therapies:

•  Immunotherapy

•  Cell therapy

•  Gene therapy

•  Regenerative medicine

•  Antibody drug conjugates

Personalized Medicine: Have we arrived?

Blood thinners

•  Coumadin: Works well, but narrow “therapeutic window,” risk of bleeding. Genetic variants in 2C9 and vitamin K genes influence response, guide dosing

•  Plavix: Genetic testing for 2C19 may identify patients who may not respond

HIV treatment

•  Ziagen: before prescribing, doctors now routinely test for a genetic variant that makes you more likely to have side effects from the drug

•  Codeine: certain 2D6 mutations result in no analgesia, others result in side effects

Pharmacogenetics: Progress thus far

Cancer

•  Herceptin: Only works for women with HER2+ breast cancer

•  Iressa & Tarceva: Work much better for lung cancer with specific genetic variants

•  Erbitux & Vecitibix: Don’t work for 40% of colon cancers where the tumors have specific genetic mutations

Neurology

•  Tegretol: Genetic variant (HLA-B*1502) increases risk for Stevens-Johnson syndrome

Psychiatry

•  Celexa: 2C19 affects dosing, ABCB1 gene alters response

More progress in Pharmacogenomics

•  “Junk” DNA matters

•  Genomes England: 100K genome project

•  Human epigenome project

•  Human microbiome project

•  Human proteome project

•  $100 million Obama BRAIN project

Still Learning: Beyond Genomics

Can we make healthcare more predictive & preventive to reverse or halt disease before it occurs and becomes too hard and costly to

treat?

•  The creative realization/consumerization of medicine: Retail healthcare is front-line

•  Decision-making shifts from doctors to patients & machine intelligence

•  Flood of data from sensors/apps

•  Price transparency (healthcare now is a menu without prices)

•  Reward for being healthy

What does the future of healthcare look like?

•  What does the $1,000 genome mean?

•  Now cheaper to do the whole genome than certain single gene tests

•  Newborn genome sequencing

•  Before long, everyone will get their genome sequenced and you (& your doctor) will query it at every important medical event throughout your life

The Future of Genomic Medicine

“One can imagine a day when every newborn will have their genome sequenced at birth, and it would become a part of the electronic health record that could be used throughout the rest of the child’s life both to think about better prevention but also to be more alert to early clinical manifestations of a disease.” Alan Guttmacher Director, U.S. National Institute of Child Health and Human Development

Newborn sequencing

•  > 4 million babies are born each year in the U.S.

•  1/20 babies born is admitted to the NICU

•  1/3 of babies admitted to a NICU have genetic diseases

•  Every night in the NICU costs > $10,000

Rapid Sequencing in the Newborn ICU

•  > 3,500 single-gene diseases have been characterized

•  Traditional genetic testing is only available for some. And how do you pick the rights test(s)?

•  Most genetic tests cost hundreds, even thousands of dollars each

•  At least 500 of these genetic diseases have a known treatment

Why sequence newborns?

•  Babies born with the rare genetic disorder phenylketonuria (PKU) are unable to break down a certain amino acid, which can lead to brain damage and seizures

•  If found early enough, PKU is easily treated and children can move on with their lives

NICU Sequencing: PKU

•  Muscle contractions due to mutations in the sepiapterin reductase gene respond to drugs that are ineffective against other movement disorders that may look the same, but have a different genetic underpinning

NICU Sequencing: SPR Deficiency

•  Symptoms of many genetic conditions, such as Charcot-Marie-Tooth (CMT), sometimes do not present until adulthood so a genetic test early-on could help to save the lives of older individuals

NICU Sequencing: CMT Disease

Newborn sequencing “Overall, [newborn sequencing] can save time, it can save lives, and a lot of times, it can save suffering.” Dr. Stephen Kingsmore Director, Center for Pediatric Genomic Medicine, Children’s Mercy Hospital

•  Information is more valuable when shared

•  Metcalfe’s law: the value of a network is proportional to the square of the number of connected users of the system (n²)

•  Free the Data: Move from genetic scarcity to genetic abundance

•  Secrecy & silos hinder scientific progress

Data sharing & open access

Reid J. Robison, MD MBA reid@tutegenomics.com

Photo Credits •  Man and Helix - http://d1435t697bgi2o.cloudfront.net/wp-content/uploads/2013/05/personalized-

medicine.jpg

•  'Your Name Here' pill - http://www.genomicslawreport.com/wp-content/uploads/2011/06/Personalized-Medicine.jpg

•  Blue pills - http://mylocalhealthguide.com/wp-content/uploads/2011/05/Pills-http-www.sxc.huprofilepawel_231.jpg

•  FDA logo - http://www.fda.gov/graphics/FDAlogos1999/graphics/logo1c.gif

•  Cystic Fibrosis Foundation logo - http://fightcf.cff.org/gs13/image/national/cystic-fibrosis-foundation-2x.png

•  Pfizer logo - http://globalgenes.org/wp-content/uploads/2011/06/pfizer-logo.jpg

•  Sovaldi bottle - http://www.gannett-cdn.com/-mm-/b0a6e4c13b58024c480e09bb1b15d165a6b5c0a2/c=0-86-3000-2336&r=x404&c=534x401/local/-/media/Phoenix/2014/06/19/pnihepatitisdrug0620secondary.jpg

•  DNA in syringe - http://cdn.static-economist.com/sites/default/files/images/2014/03/blogs/economist-explains/20140322_stp502.jpg

•  Stem cells - http://www.bitlifesciences.com/rmsc2014/images/gd/gd_2.jpg

•  Organs in petri dishes - http://media4.s-nbcnews.com/j/MSNBC/Components/Photo/_new/120910-hlt-regenerative-medicine-kb-1250p-4x3.grid-6x2.jpg

•  Human Epigenome Project logo - http://www.epigenome.org/images/HEC_title_B.gif

•  Newborn in DNA blanket - http://news.recombine.com/wp-content/uploads/2013/09/BabySeq.png

•  Newborn in incubator - http://www.nicuhelpinghands.org/wp-content/uploads/2013/02/20110923Gramkow0005.jpg

•  PKU test - http://upload.wikimedia.org/wikipedia/commons/1/16/Phenylketonuria_testing.jpg

•  Sepiaterin reductase - http://en.wikipedia.org/wiki/Sepiapterin_reductase#mediaviewer/File:Protein_SPR_PDB_1z6z.png

•  Charcot-Marie-Tooth disease - http://charcotmarietoothdisease.org/wp-content/uploads/2012/08/marie-charcot-tooth-disease.jpg

•  Purple chromosome - http://www.newautism.com/wp-content/uploads/2010/03/chromosome-300x272.jpg

•  Free the Data lock - http://ganis.spno.ca/wp-content/uploads/2012/02/data-unlocked.png

Photo Credits - cont’d