Treating haemophilia with gene therapy is a powerful option, but patients only get one chance

Gene therapy has emerged as a novel approach in treating haemophilia. Rather than simply managing the disorder, this technique aims to correct an abnormality or malfunction in the patient’s body by using a vector to deliver corrected genetic material.

While not considered a last-resort option, it is currently a one-time-only treatment. The weight of this decision is further heightened by study findings that suggest a five-year window of enhanced quality of life before efficacy declines to the patient's initial state. For those living with haemophilia, particularly younger individuals, the choice is far from simple.

What is haemophilia?

Haemophilia is a blood disorder in which an individual typically lacks one of two clotting factors: factor VIII or factor IX. Without these factors, the body cannot clot properly when faced with injuries like cuts, bruises, bloody noses, or even during routine dental work.

Traditional treatment requires patients to consistently replace the missing clotting factor by administering intravenous infusions two or three times per week. While it’s not overly complicated — children are capable of treating themselves — it does involve routine maintenance and a constant awareness of potential risks in everyday activities.

Early treatments relied on transfusions and donor-derived factor concentrates, but the inadvertent transmission of hepatitis and HIV through these products was problematic. The most notable case involved Ryan White, who was diagnosed with AIDS in 1984. The majority of patients today use recombinant factor concentrate, which is produced in a laboratory and does not carry the risk of virus transmission.

What is the cost?

Administering factor two or three times a week can cost up to $600,000 per year. Patient assistance programmes help offset the expense, but it remains a significant burden for healthcare payers. Many patients will need to seek Medicaid benefits.

The current FDA-approved gene therapy for haemophilia B, Hemgenix, is priced at around $3.5 million. Healthcare payers are faced with deciding which patients should have coverage for this new treatment: $3.5 million divided by $600,000 equates to roughly six years of pharmacy expenses offset by the gene therapy. If gene therapy cured haemophilia, then the choice would be clear. However, if the therapy's effectiveness doesn't last long enough for payers to recoup costs, it raises questions about the cost benefit of gene therapy in haemophilia and its place in therapy.

Does gene therapy work?

However, after two years, studies have indicated that those increases in coagulation factor production steadily declined, with some levels around only half of those originally achieved in the first year. Although the response to treatment was deteriorating, the patients' levels remained in a mild state of haemophilia and nearly all of them did not require routine factor replacement infusions. 

It is not surprising to see that the effects will degrade over time, as it's typical for a declining level of response to occur in gene therapy - likely due to an immune response or the high rate of cellular turnover in the liver, where these treatments do most of their work. Currently, the predicted window of efficacy appears to be around five to eight years. So far, only three years of data have been collected and ongoing trials aim to provide a better understanding of the long-term outcomes.

Is gene therapy a last resort?

It's not a last resort to the extent that patients feel they have no other options. Rather, it is an alternative for those seeking to improve their quality of life. It helps to manage haemophilia, at least temporarily, by reducing the time, resources, and financial burden associated with traditional treatments.

After undergoing gene therapy, patients no longer need prophylactic factor infusions. They still have the option of intravenously injecting factor if they get injured and there's bleeding, but their daily lives become less restricted. That puts playing sports back on the table, and they can feel secure in pursuing careers in fields where minor physical injuries are more common, like construction or carpentry.

Why is gene therapy a one-time-only treatment?

The vector is a virus that circulates throughout the body, delivering genetic material to the liver. However, the impact of this virus on the rest of the body remains uncertain. Patients may have developed immunity to the vector due to prior exposure, which could lead to their immune system fighting off the therapy and reducing its effectiveness.

Introducing genetic material into your body also carries the risk of additional mutations, possibly leading to the development of cancers. If the patient is given a second injection, their immune system may attack the vector and genetic material, negating the therapy’s benefits. Essentially, the patient’s immune system prevents successful repeat gene therapy treatments.

Long-term effects of gene therapy are still unknown, as patients in studies have not undergone biopsies to study what is happening at the cellular level. The current approach is to track patients over time and observe any developments. To introduce multiple layers or multiple variants of genetic material without the knowledge of what it’s doing to the body would compound the risk.

However, there is a glimmer of hope that gene therapy won’t always be a one-shot option. Researchers are exploring ways to remove antibodies from patients’ blood and experimenting with synthetic vectors that do not trigger an immune response.

It’s not unrealistic to think that in the future haemophiliacs could undergo gene therapy every six to eight years to maintain quality of life. However, payers, including health plans and plan sponsors, would bear the cost of these expensive treatments, which start in the millions of dollars.

How does one make this decision?

This is the million-dollar question. Is it worth waiting for advancements in technology, or should patients with a significantly diminished quality of life opt for gene therapy now?

Some patients will be candidates for gene therapy solely based on the severity of their condition and inability to properly manage it with current standard treatments. If someone’s mental health is strongly affected by a physical condition, it’s difficult to discourage them from a treatment that’s been proven to improve their quality of life, even if temporarily. 

To decide whether it’s time for a one-time-only intervention, patients, with guidance from their provider, need to carefully evaluate their reasons for feeling unable to continue managing their haemophilia using established treatments. Unfortunately, with gene therapy there are no do-overs, and the treatment cannot be undone.  

About the author

Jason Peterson RPh is a clinical pharmacist at RemedyOne, with over 25 years of experience in healthcare and pharmacy.