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The Era of One-Shot, Multimillion-Dollar Genetic Cures Is Here

SOME OF STEVEN Pipe’s hemophilia patients consider themselves cured. In a trial Pipe led from 2018 to 2021, they received a one-time gene therapy meant to override a DNA mutation that causes spontaneous bleeding episodes, some of them severe and life-threatening. Unlike most drugs, which relieve symptoms, gene therapy addresses the underlying cause of a disease. Thanks to the treatment, they haven’t had to worry about serious bleeding for years. 

“They don’t have to think about their hemophilia anymore,” says Pipe, a hematologist at the University of Michigan Health System. “For all intents and purposes, this looks like a cure.” 

The therapy, called Hemgenix, gained US approval from the Food and Drug Administration on November 22 to treat patients with severe hemophilia B. Shortly after its approval, CSL Behring, the pharmaceutical company commercializing the drug, announced its price: $3.5 million for a one-time dose. It’s now the most expensive drug in the world. As part of a research study, Pipe’s trial participants didn’t have to pay for the therapy. But future patients and their insurers will. 

It’s not clear yet if this single infusion will last for a lifetime, but Pipe says that some patients dosed in earlier trials more than 10 years ago are still keeping bleeds at bay. And to gene therapy experts, the price tag is not a surprise. “This is super reasonable, super expected. It’s a very fair price,” says Nicole Paulk, assistant professor of gene therapy at the University of California, San Francisco. 

Even at this ticket price, the approval is a milestone for patients. Over time, the repeated bleeding of hemophilia B causes pain and mobility issues, and the risk of bleeding means many patients have to avoid sports and other active hobbies. “Bleeding can be trivial, bruising. Or it could be a nuisance, like nose bleeding. But bleeding in the joints, knees, elbows, and ankles can cause crippling arthritis, and it can be fatal when it’s into the brain,” says Len Valentino, a hematologist and CEO of the National Hemophilia Foundation. Preventing those bleeds can have a huge effect on a patient’s life.  

Hemophilia B is caused by a mutation in a gene called F9. This defect shuts down the production of an essential protein needed for blood clotting called Factor IX. To prevent bleeding, patients currently have to get regular IV infusions of Factor IX. Because of the relatively short time the protein spends in the bloodstream, it has to be administered at least once a week. “A patient with severe hemophilia B might need to get injections of the clotting factor concentrate two or three times a week for their entire lifetime. That’s a significant burden,” Valentino says. 

A 2016 analysis in The American Journal of Managed Care found that these infusions cost patients an average of $127,194 per year. For those with severe and moderately severe hemophilia B, treatment can cost $300,000 or more, according to a 2021 study in the Journal of Medical Economics.

Researchers have long sought a one-and-done treatment for hemophilia: If they could fix this mutation by delivering a healthy version of the F9 gene, they could get the body to start making the protein again. “Instead of giving 100 to 150 injections per year, an individual would be able to receive one injection, and hopefully that will last indefinitely,” Valentino says of Hemgenix. “I’m a little hesitant to say a lifetime, but that’s what we’re hoping for.”

Several groups have launched gene therapy trials for hemophilia, with the first in 1998. But an effective approach took time to materialize. In 2020, CSL Behring acquired Hemgenix from a company called uniQure, which had been developing it since 2008. The therapy works by delivering a replacement F9 gene to the liver so that it can make Factor IX. The dose is delivered via an IV infusion into the arm.

The therapy isn’t a cure for all patients. In the study Pipe led, Hemgenix decreased the number of annual bleeding events by 54 percent compared to the period before patients received the drug. Ultimately, 94 percent—51 out of 54—of treated patients went off Factor IX infusions completely because they no longer needed them, according to trial results submitted to the FDA.

Hemgenix isn’t the only gene therapy with a sky-high price. Luxturna, the first such treatment approved to fix an inherited trait—a rare form of vision loss—debuted in 2018 at $425,000 per eye. The therapy is meant to restore eyesight in people with a specific genetic mutation that causes the retina to degrade over time. 

In 2019, pharma company Novartis won FDA approval for its gene therapy Zolgensma, which is meant to treat children under age 2 with spinal muscular atrophy, or SMA, a leading genetic cause of infant mortality. Novartis subsequently priced the therapy at $2.1 million, making it the most expensive drug on the market at the time. But earlier this year, newly approved gene therapy Zynteglo grabbed the title, at $2.8 million. The drug is for patients with a blood disorder called beta thalassemia who require regular blood transfusions.

All these therapies work by delivering a normal copy of the disease-causing gene to the body to counteract the mutated version. And in many cases, the drugs are life-changing—restoring vision or freeing patients from regular, burdensome treatments. In the case of Zolgensma, the drug is a literal lifesaver. Most children with SMA die by age 2. Those who get the drug can speak and sit on their own—milestones they would have never reached before. 

The companies behind these therapies have justified their high prices, saying they provide immense benefits and are more cost-effective than current treatments since they are given just once. In a company statement provided to WIRED, CSL Behring justified the steep price tag for Hemgenix: “We are confident this price point will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of hemophilia B by reducing annual bleed rates, reducing or eliminating prophylactic therapy, and generating elevated Factor IX levels that last for years.”  

The company said the price was determined with consideration of the “clinical, societal, economic, and innovative value represented by this novel gene therapy.” Earlier last month, the Institute for Clinical and Economic Review, a Boston-based nonprofit research institute that estimates the value of drugs and other medical services, said Hemgenix would be fairly priced at upward of $2.9 million.

But Michael Gusmano, professor of health policy at Lehigh University and a research scholar at the Hastings Center, an independent bioethics research institute in Garrison, New York, says the price of Hemgenix and other gene therapies shouldn’t be considered a bargain. “It assumes that the price of current treatments are appropriate,” he says. “We have a system in which prices are completely out of line internationally,” noting that the US, unlike other economically developed countries, does not regulate or negotiate the prices of new drugs when they come onto the market.

While most patients never pay the full cost of drugs out of pocket, people who are uninsured and those with high-deductive plans may have trouble accessing these therapies. CSL Behring says it plans to offer discounts, and other makers of gene therapies have also set up patient assistance programs.  

In its statement to WIRED, CSL Behring said the overall effect on the health care system will be small, since hemophilia B is a rare disease affecting only about 6,000 individuals in the US. Only adults are eligible to receive Hemgenix, making the pool of potential patients even smaller. 

Paulk says gene therapies are so expensive because they’re complex and costly to manufacture. “This isn’t a small molecule drug like Tylenol,” she says. “These are very different from your classic drugs you take in pill form. Those types of drugs can often be manufactured by robots, there can often be millions of doses made a day, and the process can be farmed out to third parties once you’ve got that chemical synthesis set.”

Gene therapies are made by inactivating viruses and using them as delivery devices to shuttle therapeutic genes to patients’ cells. These viruses are grown in huge stainless steel vats and later purified and tested to make sure they’re safe and function properly. All in all, it can take 10 months or longer to make enough doses for patients in a clinical trial. 

Even though these treatments have been in development for several decades, gene therapy is still very new to the market. Paulk thinks the cost of manufacturing will go down—and subsequently, so will the price of gene therapy—as companies get more experienced in making them at scale. “We will absolutely get better at this,” she says, but it could take five to 10 years for that to happen. 

With hundreds of gene therapies in the pipeline and some of them likely to be approved in the coming years, that could mean more multimillion-dollar treatments coming onto the market. Companies are banking on these therapies working long-term, but there’s still uncertainty about how long their effects will last. Clinical trials have followed patients for years, not decades.

If they don’t last as long as hoped, Gusmano wonders what that will mean for pricing. And even if they do, he says, million-dollar price tags aren’t sustainable in the long run. “There’s no question that these gene therapies are going to be expensive,” Gusmano says. “The question is: At what level will payers start pushing back and simply refuse to cover them?”

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