This gene therapy costs $5 million a dose. Is it worth the price?

2 months ago 20

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Born in 1949, Chip Hailey is old enough to remember when there were no good treatments for the disease written into his genes.

Haemophilia is a disease written into the genes. But there are scientific advancements.

Hailey’s X chromosome has a typo within the F9 gene that codes the protein that makes our blood clot.

When he bleeds, he keeps bleeding and bleeding, from cuts to the skin but also internally, into his joints, which swell and hurt.

Hailey, 76, has lived through just about every era of haemophilia treatment. This new one might be his favourite.

As part of a clinical trial, CSL scientists snuck an artificial virus into Hailey’s liver, where it opened and released a payload: an engineered gene, containing instructions to make the protein – known as factor IX – Hailey lacks.

It seems to be working. Hailey has spent his life having intravenous infusions of factor IX every week; now his body makes so much, the last time he needed a boost was in December 2019.

“Going from 1 per cent to 20 per cent,” he says, “you can’t imagine.”

CSL’s therapy, Hemgenix, is at the forefront of a new wave of treatments for inherited diseases. Rather than treating the symptoms, they try to change the erroneous genetic code that causes them.

The potential is enormous. But Hemgenix and its cousins also pose a challenge to Australia’s system of universal healthcare because they are extraordinarily expensive. Hemgenix costs about $5 million a dose.

So far, government bureaucrats have knocked back CSL’s request for subsidy, unconvinced the sky-high price is worth the benefit.

CSL argues Hemgenix is a permanent treatment and the $5 million upfront price is worth it when considering the long-term costs to the healthcare system of patients needing weekly factor IX infusions.

To bolster that argument, the company can now point to data published this week in the New England Journal of Medicine showing the treatment more than halved patients’ bleeding rates and cut the use of factor IX by 96 per cent in the five years following the drug being administered.

Haemophilia B is caused by mutations to the gene that codes for a protein that helps our blood clot, known as factor 11. Without natural factor 11, most people with haemophilia get regular infusions.

Hemgenix works by packaging a working human gene for factor 11 inside an adenovirus. After injection, the virus infects the cells of the liver, delivering the new gene to the nucleus of the cells.

CSL argues Hemgenix is a permanent treatment and its $5 million upfront price is worth it.

The patient’s DNA is usually not directly altered. Instead, the new gene seems to float alongside the existing genetic code.

The inserted gene itself has been modified to dramatically increase the amount of factor 11 it encodes. Professor Ian Alexander, the head of gene therapy research at the Children’s Medical Research Institute, terms it a “super copy” (he was not involved in the study).

A 2023 phase III trial of Hemgenix showed the therapy cut bleeding rates by 64 per cent in the 18 months after treatment.

But gene therapy comes with risks, in particular liver toxicity. Four children died from liver dysfunction in a 2020 trial. Twenty per cent of CSL’s study patients had elevated liver enzymes, which required treatment; one of those patients had his levels of factor IX drop over time.

Liver toxicity is a risk of gene therapy.

Because the new gene is not directly inserted into the patient’s DNA, the question has always been longevity. Will the immune system find and get rid of the new gene, or will its effects fade?

There’s little sign of that happening in CSL’s new study. The company’s head of medical affairs, Deborah Long, called the data “incredibly convincing around that long-term safety and efficacy”.

“You could have an injection-free lifestyle,” Long said.

It’s not clear if that will be a convincing argument for the drug regulators who hold the public-subsidy purse-strings.

But there’s another issue that worries Alan Dursun, the president of Haemophilia Foundation Australia. When a gene therapy is delivered, the immune system naturally raises antibodies to the adenovirus used to deliver the gene.

That may mean you only get one shot at a treatment.

“Do we wait for a better gene therapy?” asks Dursun, who has haemophilia A. “I love the idea of not having to medicate as frequently. But at the same time, if it’s only going to last a couple of years, do I really want to do it? Or do I wait for something better?

“Why fix it if it’s not broken?”

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