ICER’s Positive Cost-Effectiveness Assessment Lends Support For New Sickle Cell Disease Gene Therapies

Last month, the Institute for Clinical and Economic Review (ICER) issued a draft report on the cost-effectiveness of bluebird bio’s lovo-cel (lovotibeglogene autotemcel) and Vertex/CRISPR’s exagamglogene autotemcel (exa-cel). These are two promising investigational one-time gene therapies for patients suffering from sickle cell disease (SCD).

There are approximately 100,000 patients with SCD in the U.S. Recent surveys from around the globe reveal the extensive unmet need in the SCD space. In the U.S., approximately 25,000 patients would be eligible for gene therapy. If successful, such treatments would address some of the acute and chronic challenges facing patients.

Besides the positive news regarding the gene therapies’ cost-effectiveness, the treatments are also providing the intangible, yet important, benefit of hope for patients who’ve suffered in agony for so long.

In early April, Vertex announced it had completed its rolling Biologics License Application (BLA) submission for exa-cel. It is seeking approval for exa-cel in two different indications: Beta thalassemia and SCD. Vertex hopes for approval by the fourth quarter of this year. The completion of bluebird bio’s BLA filing for lovo-cel for SCD is still on hold. Nevertheless, if all goes as planned for bluebird bio, lovo-cel could also be approved by the fourth quarter of this year.

Even at the placeholder price of nearly $2 million per dose, ICER says both treatments could be cost-effective once approved by the Food and Drug Administration (FDA).

This is not the first time a very expensive one-off gene therapy has been deemed cost-effective by ICER.

In 2019, ICER evaluated Phase 3 evidence to calculate the cost-effectiveness of Zolgensma (onasemnogene abeparvovec), a treatment for pediatric spinal muscular atrophy. ICER estimated a value-based price for Zolgensma at between $1.2 million to $2.1 million, given a cost-effectiveness threshold of $100,000 to $150,000 per life year gained. Ultimately, the launch price chosen by the product’s sponsor, Novartis, after its FDA approval in 2019, reflected the upper bound in ICER’s calculations of what constitutes a cost-effective price.

In 2022, ICER deemed another gene therapy, Zynteglo (betibeglogene autotemcel), to be cost-effective despite the $2.5 million price tag. In August of last year, bluebird bio obtained FDA approval for Zynteglo, which is indicated for beta thalassemia.

And, later last year, ICER also determined that it would be “fair” for Hemgenix (etranacogene dezaparvovec), indicated for hemophilia B, to be priced at or near $2.9 million. While the cited launch price of $3.5 million is higher, ICER made it clear that Hemgenix could become cost-effective should the product turn out to be durable over time.

In each assessment, ICER cautioned that a prerequisite for these therapies’ cost-effectiveness was their durability and the establishment of value-based pricing agreements between payers and sponsors.

So, from Zolgensma, to Zynteglo, to Hemgenix, ICER has determined that the disclosed list prices are at least close to being considered “fair,” meaning aligned with value.

True to form, perhaps, two late-stage gene therapies for patients suffering from SCD – lovo-cel and exa-cel – also passed ICER’s litmus test for cost-effectiveness.

It’s known that treatments with high per unit prices can nonetheless be cost-effective. After all, there are two sides to the cost-effectiveness ratio. Relatively expensive hepatitis C and HIV drugs, for example, but also chronic myeloid leukemia therapeutics, are cost-effective. In part this is due to the considerable benefits provided by these treatments. But it also owes to the ability of these pharmaceuticals to displace other costs in the system, including hospital inpatient and outpatient clinic costs.

Interestingly, lovo-cel and exa-cel even meet ICER’s budgetary threshold, despite the potential market for SCD products being rather large. The ICER report suggests that “… those who are most likely to be eligible for treatment with lovo-cel or exa-cel number between 20,000 and 25,000 people in the U.S.”

In the case of both lovo-cel and exa-cel, ICER noted that the proportion of patients achieving treatment success was estimated at 97% for both therapies. At a price of $2 million per treatment course for lovo-cel or exa-cel, approximately 15% of people could be treated over the span of five years without crossing ICER’s budget impact threshold of $777 million per year. To arrive at this number, ICER estimates the growth in drug spending per year and divides that increase by the expected new molecular entrants into the market. This then becomes a budget “threshold.”

As a cost-effectiveness watchdog, ICER has no vested interest in cell or gene therapies other than to determine their estimated value. Whatever criticism one has of ICER’s methodology, surely the organization doesn’t have a drug industry bias. And so when an ICER’s value calculation appears relatively favorable with respect to certain products, this can be seen as credible supportive evidence.

Of course, cost-effectiveness and budgetary thresholds aren’t the only hurdles facing loco-cel, exa-cel, and Zynteglo. According to Courtney Rice, Principal at Acadia Strategy Partners, all three therapies rely on a myeloablative busulfan conditioning regimen, which can have severe adverse effects, including infertility. As such, this constitutes another potential barrier for patient uptake. Nonetheless, as Rice and other experts point out, the important takeaway is that these gene therapies can be cost-effective and don’t necessarily break the bank.

Too often the discussion of a therapeutic’s price is fixated on eye-popping numbers and not value. It’s laudable that ICER has redirected us to the discussion of value. In some instances, high prices may be justified by value; in others, not. At the same time, low-priced products may sometimes produce great value, and in other instances no added value at all.