Gene Therapy: An Oasis or Mirage?

Gene Therapy: An Oasis or Mirage?

By Ray Stanhope, former Chairman of the National Hemophilia Foundation Board of Directors

Now that one of the long-awaited gene therapies for hemophilia B has been approved by the Food and Drug Administration (FDA) pricing out at somewhere between $2.9M to $3.5M, I have been wondering if this really is the landscape that we envisioned back in the mid 1990’s when we started down this path.

A little background, I am a person with severe hemophilia B that barely survived to be five years old from a bleed. I have served the bleeding disorders community in and out of leadership roles for the past thirty years and I was in leadership when the National Hemophilia Foundation Board of Directors voted to start the first ever campaign to raise $5M to promote research for a cure specifically in gene therapy in the mid 1990’s. This was the first ever campaign by the foundation of its type and a challenge to the community to achieve within five years. With overwhelming support, it was accomplished within three years.

Back in the early days of gene therapy for hemophilia, it was referred to as a cure. As the decades of research progressed, it became apparent that it might be a long-lasting treatment rather than a cure. Beyond the price tag, there are a few additional exclusions with the current gene insertion treatment that were not even a consideration when we started searching for a cure. These exclusions are eligibility to receive the treatment which includes age, immune response to the viral vector, price and who will pay for it, durability, which is the persistence of the treatment over time, and has ramifications on payor consideration to approve paying for this treatment. I have chosen to use a decade as a cutoff point for durability, for the payors, given that the average adult cost of factor replacement therapy today, is estimated to be between $300,000 and $500,000 annually. This puts the pricing of gene therapy in line with these estimates over that number of years. Now let us address each of these exclusions.

ELIGIBILITY: At the start no one envisioned a future where NOT everyone would be eligible to receive this life-changing treatment. The reality of today’s treatment is no one under the age of eighteen is eligible to receive this current gene therapy. The primary reason for this is simply that the cells being infected by the vector to insert the gene are liver cells, and the liver does not reach full size until around the age of eighteen. A growing liver would decrease the durability of therapeutic levels because this treatment would not be passed on when a cell divides, hence the decrease in factor levels over time would be the result. This also means that children will be on current regimens until they are of age, but as we know, the bane of current prophylaxis is trough levels required to prevent joint damage. Also, a healthy liver, to some degree, would be necessary to be eligible, which may exclude some older people with hemophilia who have had multiple bouts with hepatitis from previous treatment options. This may require additional testing to determine the health of the liver and eligibility. If the individual has a high titer immune response to the viral vector this too will be a barrier to being eligible to receive this treatment.

PRICE and who will pay for an expensive treatment that has any failure rate and an uncertain durability timeline:

To evaluate this, we will only be considering the United States health care system of payment for treatments. Within this system we have public and private payors. Within the private payors are insurance companies and self-insured employers to consider. The public sector of payors includes Medicare, Medicaid, and state programs which have limits on available resources. Insurance companies are in the business of making money which could be negatively impacted by paying for a treatment that fails or does not persist at therapeutic levels for at least a decade. Self-insuring companies are employers that pay for the cost of their employees’ healthcare themselves, usually administered by an insurance company. Many of these payors currently balk at the cost of the current day prophylaxis factor replacement therapies on the market, causing patients and clinic staff to jump through hoops to gain approval. There needs to be a structured agreement between the pharmaceutical companies and the payors, where there is an ability to claw back funds for outright failures and a prorated refunds for those cases where durability is less than a decade and factor replacement is once again required. Without this, I see very few having access to gene therapy at current pricing. Complicating this further, is the question of how paying for a treatment today, that has years of benefits, is applicable to the private payor when the patient can change insurance companies or a new employer any time after the treatment? For insurance companies, this point might balance out because they may gain a new client who has had this treatment for everyone that chooses to move on. For employers, this picture is far less clear.

In addition to eligibility and funding mechanisms for this treatment, there are other barriers to receiving gene therapy as a treatment option, which is ACCESS:

Not every Hemophilia Treatment Center (HTC) has the ability or desire to build out the infrastructure to deliver this treatment because of the necessary handling requirements. Therefore, we may be facing the possibility of having HTCs with the capabilities to service a regional area, and this poses several issues. The first is, which HTC will be doing the follow up appointments and how will the center that delivers the treatment get reimbursed for the care they provide. This is of specific concern if the person comes from out of state.

Secondly is the issue of access on two fronts, one, being not every person with a bleeding disorder is seen at an HTC, and two, not everyone will have the resources to travel to an HTC that might be providing this treatment. These barriers are being worked on and should be overcome with time, except for the people with hemophilia who do not get their care from an HTC.

The effects of this treatment for the individual who is eligible, has a sustained therapeutic response, and the resources to access this treatment, will be profound and life changing. However, the concern for getting young people to the age of eligibility with healthy joints will continue to be a challenge. What happens to the people who fail this treatment going forward because their immune system will prevent using this viral vector again? This also applies to those who get a factor level that diminishes over time.

A final note: at the time, the NHF Board of Directors took its first vote to approve pursuing a cure for hemophilia, we never envisioned the issues and barriers present in the landscape facing us today. However, this community has faced many challenges and worked tirelessly to overcome them. Therefore, the optimist in me sees the currently approved gene therapy as an oasis on our path to find a cure for all inherited bleeding disorders. But for those who are ineligible, fail treatment, lack resources, or are not treated at an HTC, it will seem like a mirage.