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What Should Gene Therapy Cost?

By the time that the FDA’s advisory committee gave a near-instantaneous and unanimous thumbs-up for gene therapy to treat a form of hereditary blindness on October 12, tears were freely flowing. Fittingly, it was World Sight Day.

The new drug, Luxturna, is a one-time injection of a working gene into the eye to treat RPE65 mutation–associated retinal dystrophy. When the final stamp of approval arrives in January, Luxturna will be the first gene therapy approved in the US for a single-gene disease.

At the FDA meeting, the presentations from ophthalmologists who’d developed Luxturna as well as researchers from sponsoring company Spark Therapeutics were exciting, but the meeting really came to life when those who’d benefited spoke.

COUNTING STARS

Dozens of people have regained vision by participating in clinical trials that began in England in 2007. Many of the newly-sighted first notice celestial bodies – sun, moon, and stars – as did Katelyn Corey, who spoke at the FDA meeting. She’s a research assistant and data analyst at the Veteran’s Administration in Los Angeles – a career that she had given up on as her vision vanished during college.

“It was October 2011. I was a sophomore majoring in public health with statistics as my minor when I realized the jig was up: I’m going blind. But it was no surprise. I’d been losing my sight my whole life,” she began.

Her father Christopher, who spoke next, traced Katelyn’s visual difficulties to infancy. As an adult, Katelyn learned to compensate, one hurdle at a time. “At first my vision loss was small things going. I couldn’t see my pen, so I used a thicker Sharpie. If the text was too small, I used larger print books.”

Like Alice in Wonderland, Katelyn had to work harder just to stay in the same place.

Katelyn quoted the Red Queen from Alice in Wonderland in describing how she coped with a fading world, having to do more to accomplish less: “Now, here, you see, it takes all the running you can do just to keep in the same place. If you want to get somewhere else, you must run at least twice as fast.”

“All that energy with dwindling vision didn’t leave room to live. I knew I could adapt to being blind, but my passions for math and science would not be realized. That was devastating. It would be one thing if I had lost vision after completing my education. But this? Even though I could keep running, I could no longer stay in place but would fall behind,” she told the group.

And that was simply unacceptable.

“I gave myself 6 months to join a clinical trial. My family had followed the RPE65 research, and I was willing to go anywhere. That November the phase 3 trial opened and I joined,” Katelyn recalled. Participants were randomized to receive treatment right away – both eyes injected, a few days apart – or to wait a year as the researchers assessed the declining vision.

Katelyn drew the short straw.

“I was randomized to the control group in November 2012. After waiting an additional year, I feared I’d no longer qualify for treatment in December 2013,” she recalled. But she did. “It was just days before my 21rst birthday. It was the best birthday I’d ever had!”

She was stunned at how rapidly her world brightened.

“Within days of the first surgery, I could see vibrant colors again. I was no longer living in a black and white film. At night I could see the sculptures in Philly, and the moon. And then there was the sun! But man, that thing is bright! I could practically feel my pupils contracting!”

Christopher has one regret – “not recording the scene after she removed the first patch in the hotel room. At 8 floors up it had only ambient light and had been total darkness for her. She began to point and name things in the room, with gasps of surprise and excitement. When she said ‘I can see my shadow!’ it was thrilling. The ability to detect such small differences was a tremendous, life-altering success,” he told the group at FDA.

When Katelyn received her masters in epidemiology this past June, Christopher looked back on her increasing difficulty in school. “The cast of her own shadow made it impossible to read. We did her homework together, every night until 11 or 12 since second grade. Even in college we did lectures over Skype. Now she does IRB (institutional review board) submissions! Others now depend on her.”

(NHGRI)

PRICE NOT SET YET

With FDA approval fast approaching, the question of Luxturna’s price looms. Around October 12 analysts predicted $1 million, a figure that echoed through social media, although Spark had been mum.

“The price of Luxturna has not yet been determined. We are committed to helping ensure patients and their families have access to our gene therapies if they are approved. We’re looking at programs that help off-set out-of-pocket costs and help cover travel costs to treatment centers,” Spark spokesperson Monique Da Silva told me.

Luxturna was in clinical trials for 9 years, and that’s expensive. Developing the vector alone can cost $500,000 to $1 million. These days families raise much of the funding for a phase 1/2 gene therapy trial, but to get through phase 3, with its expanded roster of participants, corporate support is essential.

CYSTIC FIBROSIS: A PRECEDENT?

At the present dawn of life-altering gene-based therapies, comparing costs is an apples-and-oranges exercise. A price tag of $500,000 for Luxturna would be in the ballpark of the recently FDA-approved Kymriah, to treat a form of leukemia and the first drug to use chimeric antigen receptor (CAR-T) technology. It costs $475,000 and should be necessary just once.

Glybera was the first gene therapy approved in the western world. It treats lipoprotein lipase deficiency.

Asking $1+ million can doom a drug. The first gene therapy drug approved in Europe, Glybera to treat lipoprotein lipase deficiency (a form of pancreatitis), was withdrawn due to the high cost ($1.4 million) and the small market. It’s a one-time procedure that injects the drug into many muscles.

Perhaps the high prices of Luxturna, Kymriah, and Glybera can be justified because of the one-time administration that is possible for correcting genetic instructions – compared to altering a gene’s protein product, a much more ephemeral effect. But a drug that corrects the misfolded protein that lies behind another genetic disease, cystic fibrosis, illustrates one way to contain costs.

Some people with CF take Kalydeco twice a day, as a pill or powder. Forever. While the drug certainly works, for an increasing number of mutations in the CFTR gene, it and its combinations with other drugs is a continual cost. (An intriguing aside: the qualifying mutation list grew based on bioinformatics – predicting which altered proteins would respond to the drug – rather than requiring additional clinical trials.)

REALITY CHECK

Kalydeco costs about $300,000 a year per patient. That would outpace the $1 million one-time Luxturna in just over three years.

A look at GoodRx.com is sobering: paying for a month of Kalydeco in cash, with a discount, at Target, Walmart, or CostCo, is about $24,000. But what do patients actually pay? To find out, I posted to the closed Facebook group Kalydeco Miracles.

Responses varied from zero to being asked to fork over $350,000. A woman in Australia pays $6.10 a month; people in Canada pay nothing. “It is covered by the National Health Service in England, Wales, Scotland, and Northern Ireland,” wrote another.

But government-funded healthcare doesn’t necessarily provide Kalydeco to everyone who could benefit from it; a 12-year-old denied treatment in New Zealand made headlines. The hope is that the Labour party will put treating rare diseases on the funding radar and provide Kalydeco to CF patients or make it affordable. (See Tim Caulfield’s group’s “Controversies with Kalydeco: Newspaper coverage in Canada and the United States of the cystic fibrosis ‘wonder drug.’“)

Cystic fibrosis results from an absent or malformed chloride channel.

Many on the Facebook page report that after depleting insurance coverage, a promise from Vertex Pharmaceuticals kicks in: the company pays all but $15 a month. “My insurance charges $5000 for my first fill (my deductible), and then $50 (my copay) after that. But Vertex picks up everything except for the last $15. So I pay $15 a month until I reach my out-of-pocket maximum, in about July. Then I don’t pay anything,” posted one woman. Insurance plans vary, from covering the entire cost to charging a reasonable co-pay. One parent reports coverage from three insurers and Vertex: “After each of those takes a chunk, I pay $3.50 out-of-pocket each month. The original cost is $23,734.20 per month.”

How has it been possible to keep the prices of the new CF drugs down? It’s largely thanks to a model that the Cystic Fibrosis Foundation (CFF) calls “venture philanthropy.” In 2000, CFF put out a call to drug companies, offering funding, but only two responded. CFF selected Aurora Biosciences because of their high-throughput screening program. Aurora became Vertex, which developed Kalydeco. FDA approved it on January 31, 2012.

In 2014 CFF sold royalty rights for $3.3 billion, and has been using the funds to help patients, while Vertex announced renewed patient assistance on October 17.

The CF situation is unusual and Kalydeco isn’t gene therapy. But that success story illustrates that the pharmaceutical companies that must shepherd a drug or gene therapy through the regulatory process aren’t automatically bad guys.

Let’s wait to see what happens with Luxturna before trumpeting those $1 million predictions.

Discussion
  1. […] Recently reports in the medical journals of success seem to be accelerating, despite the long regulatory pipeline. Gene therapy has had promising results for adrenoleukodystrophy, two forms of severe combined immune deficiency, and a form of inherited visual loss (RPE65 mutation–associated retinal dystrophy), while protein-refolding drugs have been working on more of the mutations that cause cystic fibrosis. […]

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