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Monday, April 2, 2018

Doctors just Used a Brand New Gene Therapy to Try to Save a Child’s Vision



Doctors just Used a Brand New Gene Therapy to Try to Save a Child’s Vision


The Potential Is Enormous
Jack Hogan has never been able to play baseball because of his poor eyesight. Now 13, Jack was born with a rare genetic disorder that has eaten away at his vision. At night, he’s fully blind, so before dark, he has to leave his friends behind and return to his family’s home in Fair Haven, New Jersey.
Jack’s parents had been told that he could be legally blind by his 20s unless a treatment became available. That day, astonishingly, has arrived.
On Tuesday, Jack became the first patient in the US to get a new gene therapy for adults and children with inherited forms of vision loss. It’s called Luxturna and was approved by the Food and Drug Administration last year as the first treatment available to treat these genetic disorders.
The treatment delivered into Jack’s left eye a synthetic version of a gene that’s important for vision — and one that Jack was missing. In a week, he’ll get the same surgery on his right eye. After he recovers from the surgeries, his peripheral vision might improve and he should be able to see more clearly at night.
“I won’t have to go in at like 8 or 7 [at night], and I can sit and watch my friends play a game or something,” he told Vox, a day after his operation at Massachusetts Eye and Ear in Boston. He may also finally be able to play baseball too — something he’s looking forward to.
Jack is now one in a small club of patients to receive the first-ever gene therapies approved by the FDA — including Luxturna, which was developed at the University of Pennsylvania and now owned by Spark Therapeutics.
“Twenty years from now, when gene therapy or gene editing drugs are widespread, we’ll look back on today and think of this as truly momentous,” said Fyodor Urnov, associate director at the Altius Institute for Biomedical Sciences.
But there’s a catch. With a price tag of $850,000 — or $425,000 per eye — Luxturna is the costliest drug ever approved for sale in the US. That means it’s completely out of reach for the vast majority of Americans who, like Jack, have genetic disorders that impair their vision.
“This is a fantastic story of tremendous innovation,” said Dr. Steve Pearson, the president of ICER, an independent research organization that evaluates the cost of drugs.
But he’s also very worried. “As a system, it feels sometimes like we’re headed 100 miles per hour at a brick wall in terms of how we are going to pay for these drugs, and how the prices can reflect what we know about their benefits for patients.”
Luxturna works by delivering patients a synthetic copy of a missing gene
About 1 in 4,000 people in the United States are born with inherited retinal diseases called retinitis pigmentosa or leber congenital amaurosis, which can be caused by dozens of genetic mutations. In a very small subset of patients, about 1,000, mutations in the RPE65 gene specifically bring on their vision problems.
RPE65 is essential for the health of the retina, the layer at the back of the eye that’s sensitive to light. “Vitamin A is the chemical that changes shape when light hits the retina,” said Jason Comander, Jack’s doctor at Massachusetts Eye and Ear. RPE65 carries the instructions needed to make the vitamin A chemical processing machinery work. People with RPE65 mutations can begin to experience losses of vision in their infancy, including the loss of peripheral vision and night vision. Most are legally blind by their 20s.
Defect of RPE genetic mutation 


 Appearance of Retina in Patient (adult) with Leber's Disease

Luxturna was designed to address the RPE65 genetic mutation — in the best cases, permanently — for patients who have RPE65-associated retinitis pigmentosa or leber congenital amaurosis. To perform the therapy, doctors take a synthetic copy of RPE65 and put it in a virus whose sole function is to deliver the new gene to the cells that support the retina. The virus is injected — in three drops of liquid — into the space underneath the retina.
“Once you put [RPE65] back in, the eye is ready to see,” Comander told Vox. “It’s potentially a one-time treatment.”
There isn’t a ton of data on the treatment. But the results from the biggest and most robust clinical trial to date are why Jack’s doctors are optimistic it will work for him.
The phase 3 clinical trial of Luxturna was conducted in 2012 and 2013 and found that 27 of the 29 patients who received the treatment gained vision over a follow-up period of at least one year, according to a test that measured their ability to see dim light. In a test of their ability to navigate independently in varying degrees of darkness, 21 of the 29 could function at the lowest light level evaluated. (The trial was small, but not unusually small in the world of rare diseases, which have few patients eligible to participate.)
There was, however, some variation in individuals’ responses. Some people had complete turnarounds. “One kid got kicked out of School for Blind because [their] vision got better,” Comander said. But another person in the trial lost visual acuity as a result of the therapy.
Researchers only have four years of follow-up data, so the very long-term outcomes of Luxturna are unknown. For now, doctors do know that the surgery also promotes cataracts, which would require additional surgery later.
“There are risks with any surgery,” Comander said. “Jack will probably have to have cataract surgery earlier than he would otherwise. But overall the ratio of potential benefits to potential risks is amazing for this. It works — it’s not even a close call as to whether people should do it or not.”
“We were very happy and grateful our son was able to receive this surgery — the first one in the US,” Jack’s mom, Jeanette Hogan, told Vox. “Everyone deserves to be able to see”
Reckoning with the cost
But not everyone who is eligible will be able to afford Luxturna. The treatment costs $850,000 — a price tag that reflects the fact that the market of patients who need the drug is small, and that the investment could have a huge potential payoff: permanently fixed vision. But it also reflects the fact that, in the US, pharmaceutical companies can essentially charge whatever they want for drugs.
In a great story, published in Stat, journalist Eric Boodman details a moment that nearly derailed Jack’s surgery — and it had nothing to do with the medicine of science. Instead, it involved Jack’s insurance company.
A few days before surgery, Comander got a call from Jack’s family insurer, asking for proof that the cause of Jack’s vision problems is indeed the RPE65 genetic mutation. They’d only cover the surgery with that evidence. Comander had to scramble to muster it — one of the many administrative challenges that came with performing the operation, he told Vox. (In the end, it’s not clear exactly how much of the cost Jack’s family’s insurance covered and his mother declined to discuss the details.)
This is just one example of the hurdles patients may face in trying to access Luxturna, even when they have health insurance.
“There’s always an annual cap on out of pocket spending, so there could be a substantial payment that eats up a family’s deductible or hits their out-of-pocket maximum,” said Pearson of ICER. And patients who have no insurance, or whose insurance companies don’t cover — or adequately — Luxturna, may be out of luck.
To address these access issues, Spark, the company that makes the drug, is exploring rebate programs for patients who don’t fully respond to the therapy. It’s also working with insurers to allow patients to pay for the drug in installments.
But these are patchwork fixes for a drug pricing system that is fundamentally broken. “If we don’t get our act together, we may hit an affordability crunch that’ll be bad for patients, it’ll be bad for manufacturers, it’ll be bad for everybody,” Pearson said. “We have a new science, and we need a new policy — in terms of looking at the pricing and payment [system] — that will be consistent [with these] innovations.”
 This application of gene therapy is just the beginning of a potential paradigm shift for the treatment of genetic diseases. How will our health financing system accomodate these treatments.  Time will tell. Will these treatments still be effective after 5, 10, ot 20 years post-treatment
















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