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Treating Hemophilia: The Impact of New Gene Therapies

By Andrew Rouff

The CDC estimates that more than 33,000 Americans are living with hemophilia, an inherited bleeding disorder which affects primarily men. Patients with hemophilia have a deficiency of the blood proteins, known as coagulation or clotting factors, that help blood to clot properly. The two most common subtypes are hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency).

While patients with mild hemophilia may have only sporadic episodes of uncontrolled bleeding, typically following injury or surgery, patients with severe hemophilia can experience spontaneous bleeding into their joints, organs and muscles, which can lead to chronic joint disease and long-term problems such as seizures, disability and paralysis.

In the past few years, the advent of new gene therapies has given patients the prospect of freedom from hemorrhaging without the need for regular therapy treatments. These costly, one-time therapies are being touted as a cure for hemophilia, but are they? And will patients be able to access them?

Let’s take a look at the history of hemophilia therapies to better understand the market factors at play.

The evolution of hemophilia treatments

Before the advent of synthetic factors, hemophiliacs were typically treated with frequent transfusions of concentrated plasma from donors. While these treatments did work, the introduction of the blood-borne viruses HIV-1 and hepatitis C devastated the hemophilia community in the 1980s; an estimated 90% of those with severe hemophilia were infected with HIV from contaminated blood.

In the 1990s, advances in recombinant DNA technology led to the FDA approval for mammalian cell-derived recombinant factors. Takeda’s Recombinate, a synthetic factor VIII, was approved in 1992, while Pfizer’s BeneFIX, a synthetic factor IX, was approved in 1997.

In the 2010s, new concentrates and bioengineered proteins with an extended half-life became available, improving treatment efficacy for hemophiliacs. Manufacturers also introduced several new non-factor treatments, such as the antibody Helimbra, which reduces the frequency of bleeding episodes in individuals with hemophilia A.

The era of genetic therapy

We’re now in the midst of another massive leap forward in hemophilia treatment. Several manufacturers are introducing gene therapies that can effectively ‘cure’ hemophilia, at least over a six- or seven-year period.

The first two, BioMarin Pharmaceutical’s Roctavian and CSL Behring’s Hemgenix, were approved in June 2023 for patients with severe hemophilia A and hemophilia B, respectively. These one-time infusion treatments contain a modified adeno-associated virus (AAV), which delivers an effective copy of the factor VIII or factor IX genes to the body’s liver cells, enabling the body to begin producing clotting factor on its own.

Several other AAV products are currently in the pipeline, including Pfizer’s fidanacogene elaparvovec, a novel gene therapy which contains a bioengineered AAV capsid along with a high-activity variant of the human factor IX gene. This therapy has been granted breakthrough, orphan drug, and regenerative medicines advanced therapy (RMAT) designations from the FDA, which is expected to review the drug within the second quarter 2024.

Access will likely prove tricky for hemophilia gene therapies that aren’t the first to market. As one payer noted to MMIT, “[This product is] pre-clinical entering markets that already have an approved gene therapy product. As such, there needs to be a greater focus on unmet need.”

The therapeutic landscape also includes new therapies with novel mechanisms of action, which provide other options for patients with both hemophilia A and B. In February 2023, the FDA approved Sanofi’s Altuviio, a high-sustained factor VIII replacement therapy that allows hemophiliacs to resume near-normal activity levels with weekly dosing. The manufacturer has also completed Phase 3 studies for fitusiran, a small interfering RNA (siRNA) therapy designed to lower levels of antithrombin, a protein that inhibits blood clotting.

Staggering cost of treatment

The promise of gene therapy has generated considerable enthusiasm in the hemophilia community, but ensuring access to these high-cost treatments is far from assured. Roctavian is priced at $2.9 million, and Hemgenix is currently the world’s most expensive drug, with a price tag of $3.5 million.

Historically, payer reimbursement for hemophilia treatment has revolved around consistent dosing on a daily, weekly, or monthly basis—which can be quite expensive over a patient’s lifetime. According to The  National Bleeding Disorders Foundation, the average cost of clotting factor therapies for patients with severe hemophilia is $600,000/year, and expenses can be much higher for the 20% of patients who have an immune response to treatment.

How will payers determine the long-term value of these new one-time therapies? In late 2022, the Institute for Clinical and Economic Review (ICER) released evidence reports assessing the comparative clinical effectiveness of both FDA-approved gene therapies. ICER set a health-benefit price benchmark (HBPB) of almost $2 million for Roctavian and almost $3 million for Hemgenix.

ICER panelists concluded that both treatments provide low to intermediate long-term value, although they noted that some patients treated with Roctavian will eventually need prophylaxis treatment again.

Flexible, clear warranty design

To persuade payers to cover expensive gene therapies, manufacturers often present financial models to demonstrate conclusive cost savings. While many payers prefer to use their own cost-utility models and cost-benefit analyses, a few are willing to use models developed by manufacturers. Models might look at factors such as the incremental cost-effectiveness ratio of each treatment option per quality-adjusted life-years gained.

As ICER recommends, both manufacturers have also developed outcomes-based warranties that offer payers money back if certain metrics are not met—a strategy that appears to be working. In a press release, CSL Behring said that payers covering 60% of American lives have established clear coverage policies for Hemgenix. In addition, numerous payers are already discussing the potential terms of a warranty for Pfizer’s impending fidanacogene elaparvovec therapy.

So what kind of factors are important to warranty design?  According to payer insights from MMIT’s Message Monitor solution, payers prefer warranties that are clearly written and communicated. The following questions should be addressed:

  • What specific metrics need to be met, and by when?
  • How much of the list price is returned if the product fails to meet these metrics?
  • How do the chosen metrics relate to clinical data?
  • Are these metrics open to negotiation, or are the terms of the warranty rigid?

Payers also need some sense of how difficult it will be for these products to meet the warranty. What is the likelihood of failure and payer reimbursement? If manufacturers cannot offer favorable warranty terms, payers are more likely to opt for stricter product management to ensure cost savings.

As the market adjusts to the changes in the hemophilia treatment paradigm, manufacturers currently developing novel gene therapies in established indications will need to learn from the BioMarin and CSL Behring playbooks. Whether these brands fail or succeed in overcoming these access hurdles will inform manufacturers’ future market access strategies for their own gene therapies.


For actionable insights into payer and IDN perspectives on gene therapies, learn more about MMIT’s Message Monitor solution.

© 2024 MMIT
Andrew Rouff

Andrew Rouff

Andrew Rouff is a senior consultant on the Advisory Services team at MMIT. A scientist by training, Andrew uses market research and analytics to help clients understand the unique opportunities and challenges in providing access for their brands. He earned a bachelor’s degree in biochemistry from Union College and a master's in bioengineering from the University of Pennsylvania.

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