Insurance companies are not allowed to deny coverage to anyone who has a pre existing condition nor can they impose lifetime or annual coverage limits.  That’s driven up the cost of health care.  Its financial impact has been evaluated by budget people and decried by some politicians, but it’s the law and for now at least, we’re dealing with it.

It’s bringing a new kind of drug into focus.  Treatments are emerging that are novel, needed, and (given our current drug pricing system) will, no doubt, be extremely expensive.  Best I can tell politicians, insurance executives… the world, has no idea what we’re about to get into and how we’re going to pay for it.

Each year 100 American babies are born with Pompe’s disease.  The children are floppy, their muscles barely work, and their heart is enlarged.  Few survive infancy.   A genetic, recessive condition, the disease is only seen when both parents carry the defective gene.

The malady is the result of an enzyme deficiency.  The kids’ cells don’t make enough lysosomal acid alpha-glucosidase, a protein that’s used to convert stored glycogen into glucose—energy.

We eat carbohydrates and sugar, and we turn what we don’t use into a storage polysaccharide called glycogen.  We stockpile the excess fuel in our muscles and liver.   Between meals, when we need sugar to keep going, we use enzymes like lysosomal acid alpha glucosidase to turn glycogen back into glucose.

Much as children with juvenile diabetes need insulin to survive, babies who lack the enzyme won’t stay alive long.

The condition was “characterized” by and named for a Dutch pathologist–Joannes Pompe.  A member of the Dutch resistance, he was executed by the Nazis in 1945.   The absent enzyme, Lysozyme, was isolated in Belgium in 1955, and the responsible GAA gene was identified in 1979.  (It differs a little from one family to another.)

The needed enzyme was first made at Duke University by a dedicated team of researchers.  Their leader, Dr. Chen, the chief pediatrician, started his quest after he went to the funeral of an infant who died of the disease.  God, the pastor said, must have given the child life for some reason.  Chen took the message to heart, and decided to assemble a team of Duke University researchers and go to work.

The inspiration came at the right time.  Researchers knew how to clone genes—how to isolate the DNA fragment that are the gene and make copies of it.  Scientists with genetic engineering training could plant the gene into a special kind of cell.  If everything went well the implanted DNA would then direct the cell to make the desired protein.

Using cells from the ovaries of Chinese Hamsters—“the workhorse behind many biotech drugs” –it took the Duke team three years to make enough special protein for their early tests.  The juice they produced was injected into a quail that had been bred to be enzyme deficient.   The poor bird was in bad shape.  It couldn’t get off its back, much less fly.  Post injection the creature stood and even flew a little.

After 6 years of successful research, the Duke scientists got some manufacturing help.  Production rights were licensed to Synpac, a British/Taiwanese company with a presence in Durham, Dukes home.  Synpac, in turn “used experienced contractors to manufacture the enzyme.”  (Having done the heavy lifting, the Duke scientists gave a lot away, but they retained some royalty rights.)

Once the company had produced enough enzyme, physicians at Duke infused the protein into three kids with Pompe’s disease.  Lysozyme replacement worked.

In 2006 Synpac made a deal with Genzyme…a “15 year royalty sharing agreement that was potentially worth $821 million.”  At the time Genzyme was huge.  Based in Boston, their 2010 revenue was $4 billion.  The company planned to spend more than $500 million dollars creating production facilities for Myozyme (their name for the enzyme).

The following year Genzyme was acquired by the French Pharmaceutical giant, Sanofi for $20 billion.  As part of the process Duke University was paid $90 million, and relinquished its royalty rights.   In 2016 Sanofi sold $800 million worth of the needed enzyme.

Now called Lumizyme, the enzyme s currently made in large sterile factories.  Babies with the disorder get an injection of the protein every two weeks.

In this country “according to Sanofi, the average annual cost of treatment is $298,000.”   If it works the first year it’s needed the second and third year.  By the time a young person is 10 years old—if no one develops a less expensive generic product, the system (insurance companies and Medicaid) will have shelled out $1 to $3 million dollars per child, and big Pharma will have been handsomely compensated.

Every so often a child is born with one of over 2000 really bad genetic diseases, and his or her family has to love, raise, and deal with a disabled infant who will die young. 

Researchers are hard at work on the problems.  In recent decades they have developed drugs/injections/treatments that supply or teaches the body to replace a vital protein. As a result the number of children currently alive with each disorder has gradually increased.  

The companies that market these life saving products charge a lot, too much for most people, so the government or private insurers are billed.  Or charities kick in.  Or kids die.   “At the current forecasted growth rate, the revenues generated by the $100+ billion orphan drug market is expected to almost double in the next 6 years.”  Since the law no longer allows insurers to limit their liability or deny coverage—the companies that stay in the market and continue to offer policies—and ultimately the taxpayers– have new flood of costs they will increasingly have to deal with.   

In the U.S. 49% of our health dollar is spent on 5% of the people.  The total cost of care in the 2 ½ decades between 1980 and 2004,”has gone from $1,106 per person ($255 billion overall) to $6,280 per person ($1.9 trillion overall).” 

In the first part of the chapter I’m going glimpse the current wave of orphan drugs.  I’ll review a few of the costly, life saving medications that insurance companies were probably beginning to fear.   In the second part I’ll suggest that gene editing will soon change the picture, and I’ll wonder how much the new treatments will cost.



There was a time when drugs for uncommon diseases had a difficult time getting FDA approval.  Tests involving large numbers of affected people were needed before the FDA would conclude a new drug was safe and effective.  That usually wasn’t possible when relatively few people were afflicted.  Families of kids with rare diseases tried to induce researchers to try to find a treatment or cure, but they weren’t very successful.   

Then parents got together, pressured members of congress, and the legislature acted.  In 1983 Congress passed and the president signed the Orphan Drug Act.  Companies that manufactured drugs for less than 200,000 Americans got a lot of goodies:  Their FDA monopoly lasted seven, not five years.  Companies got tax credits—they could write off half of the development costs.  If the disease was rare developers skipped the usual wait and joined the “fast-track” line.

            The law worked better than anyone could have predicted. There are 7,000 rare diseases affecting 25 million to 30 million Americans. In the first 20 years 249 orphan drugs were marketed. 

In 2012 the FDA approved an important cystic fibrosis drug and Vertex Pharmaceuticals priced it at $295,000 a year.  At the time insurance companies were already dealing with the cost of 7 super-orphan drugs that were more expensive than the newcomer.  Some allowed infants who once faced an early death to survive and thrive.   Life saving medications usually need to be taken periodically for a lifetime.  When 1000 infants with a fatal disease live on, they are joined by 1000 similarly afflicted newborns the following year.  As the number of survivors rise, the overall outlay by insurers increases.  As their annual expenditures go up insurers charge more.

Cystic Fibrosis had not been on the Vertex radar before 2000.  That year they purchased Aurora Biosciences Corporation, and paid $592 million in stock for a company that had a technology they wanted.  Aurora was able to screen large numbers of small molecules and find out what effect, if any, they had on target cells.

The acquisition came with a commitment.  The Cystic Fibrosis Foundation was going to give Aurora $47 million over 5 years.  The Gates foundation would kick in an additional $20 million.  In return Aurora would screen for “drug leads against four protein targets that they had identified as promising.” (The foundation’s “gene therapy” approach had been unsuccessful and they were looking for a new line of attack.  –this all happened before we knew about Crispr-Cas9–)

People’s bronchial tubes normally produce a watery secretion, and it collects bacteria and foreign particles.  Hair like cilia sweep it up and it’s swallowed or coughed out.  The lungs of kids with Cystic Fibrosis produce a thick, “glue like mucous.” It too collects foreign particles, and bacteria, but a body has a hard time getting rid of it.  People with the condition periodically develop pneumonia, and over time lose lung function.  A century or so ago, most weren’t treated with inhaled bronchodilators, physical therapy, postural drainage, and appropriate antibiotics.  Few survived childhood.

The Cystic Fibrosis Foundation has established 117 centers of excellence.  They are manned by experienced health care professionals and have guidelines, “best” practices, and public monitoring. As a result of their aggressive approach the average person with Cystic Fibrosis now lives an average of 35 years.

The foundation was looking for something better.  Aurora was going to help them decide if a pill could make a difference.

Vertex was not anxious to get into the Cystic Fibrosis business.  There were only 30,000 Americans with the condition.  If the company found a potential drug, it would cost $100,000 to test each person. As Vicky Sato, the company’s president explained to a group of business students:  “can we craft a deal that makes sense to us as a drug company?  If we commit to cystic fibrosis are we limiting our upside on drugs with bigger market potential?” (Victoria Sato, president of Vertex–Barry Werth, The Antidote. Page 69)

In the company’s mind the cost of getting involved was “prohibitive.” Richard Aldrich, a deal maker and advisor, thought Vertex should only work with the CF foundation “if they agreed to fund some of the early stage (drug) development.”

About this time Vertex hired Eric Olson and put him in charge of the project.  An experienced research biologist, he was interested in CF.  A Colleague/friend’s daughter had the disease.

The condition is genetic, and recessive.  If both parents are carriers, one of four offspring is afflicted.  The faulty piece of DNA, the cause of the disease, was located in 1989 by a group of Canadians geneticists working with Hong Kong born Lap-Chee Tsui.  The mutation responsible for most cases of cystic fibrosis occurs when three nucleotides are deleted from a gene on chromosome 7.  Called Cystic fibrosis trans-membrane conductance regulator (CFTR), the abnormal gene causes the cell to make a defective membrane protein, one that doesn’t “fold” normally.  Normally folded protein regulates the amount of chloride, salt and water that flows through the surface passage ways of the cell membrane.  In people with Cystic Fibrosis, salt accumulates outside the cell and secretions are thick.

Olson’s group isolated tiny pieces of cell membrane and “looked for electrical changes”- for a molecule that could increase the flow of chloride and liquids.   They analyzed tens of thousands of compounds before they hit on an effective molecule.  It wasn’t potent, but it increased the flow and validated their concept.  A chemical that helped the disease might be out there.  They needed to press on.

Research progressed and in May 2001 the Cystic Fibrosis Foundation gave the company “$21 million in direct research funding for the subsequent two years.”  More researchers joined the effort.  They looked for molecules that did something good to misfolded surface protein.  They sought “potentiators”, molecules that kept channels transporting chloride and liquids open longer.

In August of that year they found a potentiator that was “ten times more potent than the starting point.”  The discovery didn’t mean that a drug was around the corner, but it convinced them they were on the right track.”

By June of 2011 Vertex had two drugs that dropped the salt content of sweat.

(People with Cystic Fibrosis can’t push salt into their cells.  A drop in skin salinity meant fluids and chloride were crossing the surface membrane.)

Phase three drug trials started in 2009.  In January 2012 the FDA approved the monopoly status of Ivacaftor (Kalydeco).  A “potentiator” it increased CFTR channel open time.  In 2013 it was joined by a second molecule, VX-809, a “corrector”.  The drug does something to protein folding, and it increases the number of CFTR proteins that are brought to the cell surface.

In 2015, now marketing its Cystic Fibrosis drug, Vertex earned $1.01 billion.  In 2016 its gross profit was $1.49 billion.  For the first time in 20 years the company was making money.

Founded 28 years ago, Vertex was a corporation with great talent and ideas.  It became the focus of two books chronicling the problems of a promising startup.  In 2011, at age 22, the company was $3.6 billion in debt, and it hadn’t yet produced a significant product.  Much of its subsequent effort and money was spent developing Telaprevir.  An FDA approved drug, the medication increased the ability of interferon to cure hepatitis.    But people taking Telaprevir still needed to take interferon injections once a week for a year, and that’s hard.  When the recent generation of Hepatitis C medications hit the market, when the condition could be cured in weeks without interferon, Vertex stopped making Telaprevir. (In March of 2017 Vertex purchased another CFTR potentiator from Massachusetts based Concert Pharmaceuticals for $160 million.)

So how good are the drugs?  So far they seem to help.  Or to be technical:

The combination of two drug regimens:  either tezacaftor–ivacaftor or lumacaftor–ivacaftor “improved lung function in patients with cystic fibrosis who have the most common genotype.”  In the short run they decreased the exacerbation rate, and the unexplained “worsenings” that contributed to a more rapid decline in pulmonary function.  But the drugs’ “efficacy is suboptimal and falls within the range of established symptomatic therapies, such as nebulized inhaled hypertonic saline or recombinant human DNAse.” http://www.nejm.org/doi/full/10.1056/NEJMe1712335

 Founded in 1997 and based in San Rafael California, Biomarin is on a roll.  They’ve acquired 6 biomedical startups in the last 15 years, and in 2016 were marketing 5 orphan drugs.

One of them, Brineura, is a $700,000 a year replacement enzyme that, when injected into an affected child’s brain, gets them walking.  It was marketed in 2017.  Kids with the rare (20 American children a year) fatal (they usually die when they are 6-8) disease, can’t get rid of certain kinds of brain waste until it’s broken down, and they lack the enzyme that allows that to happen.

The responsible genetic defect was discovered in 1997 by two professors at Rutgers who had, for years, been studying lysosomal storage disease.  Using a genetically engineered mouse they produced some of the missing protein and tested it.  Replacement therapy worked, and they patented the protein.  Then they licensed BioMarin.  The company paid for the testing and marketed the drug.  The genetic defect is called Neuronal Ceroid Lipofuscinosis.


And now for the present/futureThe most common genetic cause of death in infancy, Spinal Muscular Atrophy “causes severe weakness by 6 months of age and inability to breathe by the age of two.”  The drug that saves the lives of 40+% of the one in 11,000 babies who are annually born with the condition costs $750,000 the first year.  The treatment’s creation was funded with private and public monies.

The recessive condition occurs when the gene that tells the cell to make a needed protein is “either deleted or mutated.”  There’s a backup gene.  It’s one nucleotide off– It has extra RNA nucleotides –and its RNA doesn’t work or work well. .  In normal individuals the unwanted fragments of RNA are routinely removed by splicing enzymes.  In afflicted kids they aren’t eliminated and the cell doesn’t produce enough of the needed protein.

Scientists didn’t know how to get rid of the “gibberish” nucleotides, but they developed a “patch” that allowed the RNA to function.  It was a great accomplishment and it wasn’t easy.

The basic research was performed at the Cold Spring Harbor Laboratory, a huge non profit facility in New York, by a team led by Adrian Krainer.  He’s a PHD researcher who has worked on RNA splicing off and on for 30 years.  First hearing about Spinal Muscular Atropy in 1999, his team developed a “method to correct the RNA defect in a test tube.” They applied for a patent and Isis Pharmaceuticals (now Ionis) contacted them.  In the subsequent years Krainer and Ionis worked together.

On June 23 2006 Krainer, his fellow inventors, and Ionis pharmaceuticals inc. filed the first of two patents.  (The second patent added Cold Spring.)  In their application they described “a complex process that requires a multitude of signals and protein factors to achieve appropriate mRNA splicing.”

A lot of time, effort, and money was spent developing an RNA sequence that could be injected into the spinal fluid and could save the children’s nerves and muscles.

In 2008 Cold Spring Harbor lab granted Ionis an exclusive royalty-bearing license.  The company was allowed to develop, make, have made, use, sell, offer for sale, have sold, import and export …   and Ionis agreed to provide additional funding.

I don’t know how much Ionis paid for the license and what portion of the royalties were promised to Cold Spring.   During the development phase Ionis partnered with Biogen.  There was a fifteen-month study.  126 non-ambulatory patients with later-onset SMA were treated, and the drug worked.

In 2015 Biogen paid: $75 million for an option on the drug; $150 million “in regulatory milestones”; and 10% to 15% royalties.   Biogen also paid for all development subsequent to taking the license.  (The Biogen agreement included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor and University of Massachusetts.)

In December 2016, the Ionis’ drug, nusinersen, (Spinraza) was approved by the FDA.  Biogen decided to charge $125,000 for each dose.  $750,000 per child the first year.  $375,000 each subsequent year.  (it’s given 3 times the first month, once at 2 months, then every 6 months.)  N Engl J Med 2017; 377:1723-1732

Hundreds of millions of public and private dollars were spent developing and producing the drug.  Before they even started working on Spiranza, Ionis had, over the years, gone down a few blind alleys and had developed drugs that didn’t sell well.

In her 2004 book Marcia Angell says “drug companies claim drugs are so expensive because they need to cover their very high research and development costs,” and she picks their numbers and logic apart.

The cost of the Spiranza flustered a physician at the University of Utah:  “We follow about 150 SMA patients. If each were treated with nusinersen, the cost would be $113 million the first year and $56 million thereafter (not accounting for newly diagnosed patients). Nusinersen’s extreme price is a challenge for any health care system, particularly those with an accountable care organization responsible for large numbers of patients (200,000 children in our case).”

He outlined a few solutions to high prices, none of which could come close to solving his dilemma.  His suggestions include:

Panels of experts


Making sure insurance companies understanding how valuable a drug is.

He mentioned but didn’t endorse the United Kingdom’s approach.  Before a drug is approved, the National Institute for Health and Care Excellence (NICE) has to determine its cost effectiveness or value–using quality-adjusted life years.

And he wrote about the Institute for clinical and economic review (ICER), a small Boston-based nonprofit with a NICE-like model.

In November 2017 AveXis, a (now) Dallas based company told the world about a different approach to SMA.  They placed a gene that promoted the production of the needed SMN protein into the nuclear DNA of an adenovirus.  Then they infused the virus into kids with SMA.

The 12 treated children were at least 20 months old at the time.  Kids were followed for two years.  At some point “eleven were able to sit unassisted for at least 5 seconds, 10 for at least 10 seconds, and 9 for at least 30 seconds.  11 achieved head control, 9 could roll over, and 2 were able to crawl, pull to stand, stand independently, and walk independently.  Eleven were able to speak.  Gene editing—seems to have come to the rescue.

AveXis was founded in 2010 and claims it has $75 million in funding.  This, its first product, may be a long term solution to SMA. “Two years out there was “no waning of effect or clinical regression of motor function.”  N Engl J Med 2017; 377:1713-1722.


The arrival of Gene therapy will, potentially be as transformative as penicillin was for strep throat,

OR the drugs that turned HIV, into a chronic, survivable condition,

OR the immune modulating medications that allowed transplanted organs to survive.

Each of our cells has 22,000 chains of DNA that are our genes.  Their lengths are variable, and they are scattered amidst the 6 billon DNA nucleotides.  Commonly identified by their initials: A, T, C, and G, pairs of the nucleotides—our biologic code– line up in one of the 23 chromosomes in the nucleus.   Genes are recipes – sets of instructions that tell cells how to correctly assemble proteins from amino acids.  Proteins are the workhorses and building blocks of the cells.

Much as we arrange a few of the 26 letters of the alphabet to create words, genes use arrangements of the 4 nucleotides to send instructions to RNA and on down the chain.  A misplaced letter can cause a serious problem.  For example, the mutation that causes Sickle cell anemia, a severe genetic disease, is caused by the misunderstanding caused by a single misplaced nucleotide.  There’s a T where there should be an A—(like he ate a pea not he ate a pet).

Over the years many genes were identified.  When, in 2001, the human genome project was completed, scientists started examining the 3 billion pairs of nucleotides one by one.  They detected “over four thousand different kinds of DNA mutations that can cause genetic diseases.”

The discovery of the way we currently edit genes was the result of curiosity based research performed in numerous locations.

Currently scientists seem to be using two gene editing procedures:

the “stand alone” method uses the natural inclination of viruses to enter cells, become part of their DNA and force them to crank out thousands of baby viruses.  In this case a missing gene is planted in an adenovirus, and the concoction is injected into a person.  Viral capsids enter human cells, and “use the “cell’s machinery” to “deliver a single stretch of DNA into the nucleus.  The cell’s repair mechanism sends the DNA to the targeted area—and (I’m not sure this is technically correct) the strand of DNA –the good gene—attaches and goes to work.  ”https://www.horizondiscovery.com/gene-editing/raav

Researchers are also using adenoviral vectors to deliver the genes with the tool known as CRISPR/Cas9.  http://blog.addgene.org/adenoviral-delivery-of-crisprcas9-aims-to-expand-genome-editing-to-primary-cells

Since CRISPR will probably be widely used in future gene editing, I thought I’d try to explain it.  The investigators who did many of the studies and developed the concept were publically funded and were—at the time—trying to learn how bacteria defend themselves from assaulting viruses.  They were trying to understand CRISPR.

(The following theory of how CRISPR came into being helped me understand the process.) When a bacteria is assaulted by a virus, the invader enters the cell, takes over its DNA, and directs the bacteria to make billions of viral particles.  Most of the bacteria are enslaved, then destroyed.  A few mount a defense, survive, and create a “DNA memory file.”  The identifying characteristics of the bad viruses are stored in the DNA’s CRISPR area, and it becomes one of the “genes” that are passed on to future bacteria.  In subsequent generations the memory DNA creates strands of RNA that float around inside the bacteria.  When a segment of RNA recognizes an invading virus it latches on.  Then it cuts the virus apart with an enzyme called Cas9.)

After they understood how bacteria identify and destroy unwanted viruses, a group led by UC Professor Jennifer Doudna tried to use the system to edit genes.

They chose a target–a “twenty-letter DNA sequence” that was part of the gene they wanted to delete; and they “converted” a collection of nucleotides “into a matching 20 letter strand of RNA.”

They planted the genetic instructions for making Cas9—the knife—into one plasmid.   Plasmids are segments of DNA that “exist naturally in bacteria but are not part of the nucleus.”

They put the genetic instructions for “guide RNA” –-into a second plasmid.

Doudna’s group merged the CRISPR—RNA (the RNA that targets the specific segment of DNA)—with the tracRNA (the RNA that attaches to the Cas9 nuclease–the “knife”.)

Their concoction was able to search a cell’s DNA—3 Billion pairs of nucleotides—and find the targeted segment of DNA.  Then the RNA unwound the DNA and used its Cas 9 to cut both of its strands.  In other words they irreparably damaged the gene.

In June 2012 Doudna and Charpentier published a study that showed how RNA and Cas9 could be used for “site-specific DNA cleavage and RNA-programmable genome editing”.  Investigators around the world took notice and got busy.

Scientists already knew how to add a new, good gene.  Mario Capecchi, years back learned that genes intuitively know where, amidst the 3 billion pairs of DNA nucleotides, they belong.  If good genes are developed and put into cells, they migrate and attach to “their place.”  (Mario Capecchi of the University of Utah made the discovery in 1982, and won the Nobel prize in 2007).

After Doudna’s paper was published Kevin Esvelt (currently at MIT) explained how using CRISPR + selfish genes in the germline can create changes that will be inherited by future generations of cells.

In the early 1990s, Ronald Crystal, a physician at the NIH and Cornell, first showed “adenovirus vectors were effective at transferring genes to most organs” Since that time the technique– created and developed with public monies– has been widely used.

Everything was in place.  There are a lot of genetic diseases that need to be cured.   Sensing that there wasn’t time to write grants and get government funding, Doudna and other scientists formed a venture capital company– Editas Medicine.  Charpentier and others founded CRISPR therapeutics.  (Both firms, according to their web sites, are trying to cure Sickle Cell disease, cystic fibrosis, and a few other genetic conditions.)

One of the problems tackled by other researchers was hemophilia.  It’s a genetic condition that “occurs in approximately one in 5000 live births.”  The defects are sex linked, which means that women carry the gene and their sons get the disease.  The males have one of several mutations in the genes responsible for factor 8 or factor 9.  They can’t make any or enough of one of the proteins –ingredients–that are needed to form a blood clot.

Without the needed factor injured people don’t stop bleeding.  Their joints periodically and very painfully fill up with blood.  Over time they develop joint deformities.  People with hemophilia are treated with transfusions and with infusions of the missing factor.  Some develop antibodies to the proteins, and they stop working.

Researchers at the University College London recently figured out how to fix one of the genes.  They put a factor 8–concoction into AAV5, an adeno-associated small virus.  The virus doesn’t seem to cause disease and it’s not highly immunogenic.  The details of their infusate have not been revealed.  We only know its name:  AAV5-hFVIII-SQ.  In 6 of 7 patients receiving a high dose of gene therapy “factor 8 increased to normal level and stayed there for a year.  None of the 7 treated patients bled during that year.”  It’s too early to be sure it will last, but it looks like hemophilia is curable.  After they developed their haemophilia gene treatment, UCL licensed it to the U.S. biotech company Biomarin. “The licensing led increased investment in the research and the acceleration of clinical trials.”  Nejm Dec 28, 2017.

Gene therapy for hemophilia B was developed by Spark researchers.  (Spark is a Pennsylvania startup that works with scientists from the Children’s Hospital of Philadelphia.)  10 men with hemophilia B whose blood had less than 2% of the needed clotting factor were infused with an adeno virus containing a replacement gene-technically speaking a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX–R338L) transgene.)

During the subsequent 49 weeks their clotting level rose and stayed at a mean level of 33 %.  Bleeding virtually stopped.  Only 2 patients needed a factor infusion.  NEJM Dec 7, 2017.  Again, it sounds like we’re talking cure.

In 2015 supported by NIH grants doctors introduced “The gene encoding RPE65  into the retina of patients with RPE65-associated Leber’s congenital amaurosis—a genetically caused, childhood onset, autosomal recessive blindness.  Many showed Improvement then Decline in Vision.  N Engl J Med May 14, 2015

In subsequent trials “27 of 29 young people (93%) gained vision and maintained it for at least three years.” http://www.cnn.com/2017/10/12/health/fda-gene-therapy-blindness-vote/index.html



Investigators at Emory University in Atlanta have “snipped a gene that produces toxic protein aggregates in the brains of 9-month-old mice that are used as a model for Huntington’s disease.”

People who lack the CCR5 gene are not harmed by HIV.  The virus uses the CCR5 derived cell wall protein” when it invades cells.  When the protein is absent it’s hypothesized that the virus doesn’t enter and destroy T lymphocytes, and people with HIV don’t become susceptible to a slew of organisms.  The gene is present in Africans and most Europeans.  That’s bad.  And so far no one, to my knowledge, has developed a CRISPR concoction that will destroy the CCR5 gene in people with HIV.  It’s still just a potential target.

It’s too soon to say we’ve cured hemophilia or childhood blindness.   CRISPR derived gene therapy is new and exciting and not fully developed.  We need a few more years under our belt.  In the meantime, given our current experience with the price of drugs we should start thinking about how we’re going to pay for stand alone AAV and CRISPR treatments.

(“Stuart Orkin, MD, and co-author Philip Reilly, MD, JD, of Third Rock Ventures, tried to “catalyze the discussion” by suggesting several new models for valuing, pricing and developing gene therapy.”  Good luck.

  1. H. Orkin, P. Reilly. Paying for future success in gene therapyScience, 2016;)