Roctavian

Stunning Breakthrough: Hemgenix

Laurie Kelley November 27, 2022

Last week we shared an essay by Paul Clement about the approval for gene therapy for hemophilia A, approved only in Europe, and asked, when for the US?

While that question is still valid for hemophilia A, the stunning news this week was that gene therapy–at long last—is approved, for hemophilia B!

The news straight from CSL Behring: “This historic approval provides a new treatment option that reduces the rate of annual bleeds, reduces or eliminates the need for prophylactic therapy and generates elevated and sustained factor IX levels for years after a one-time infusion.”

The news was so startling, it made front page on CNN.com. But I suspect not for the scientific reason but for the economic reason: it comes with a $3.5 million price tag, making it the most expensive drug on earth currently.

Hemophilia Economics 101

While high prices are nothing new in hemophilia—factor therapy has always been among the world’s most expensive drugs—the sticker price was shocking to many. So many people have asked me through the years when is the price of factor going to come down, as if it were a high-tech consumer item like camcorders, Walkmans or DVD players. Remember those? They get mass produced, offshored, and millions upon millions of consumers buy them, which eventually drives the price down. And don’t forget competition. Basic supply and demand.

Hemophilia drugs are nothing like that. There are many factors that determine price but here are three: the research and development (R&D) that was spent to create the drug; the finite marketplace; and whether insurance will cover the cost.

R&D for drugs such as Roctavian, the brand name of BioMarin Pharmaceutical’s gene therapy product approved in Europe for hemophilia A, and Hemgenix, the brand name of CSL Behring’s gene therapy product approved by the U.S. FDA for hemophilia B, can surge to the hundreds of millions, if not billions, of dollars. The money needs to be recouped, and reinvested in the company, and to investors.  

The smaller the target audience, the higher the price. How can you recoup the R&D with such a small consumer audience as hemophilia B? In the U.S., there are approximately 20,000 with hemophilia, of which about 15% have hemophilia B. Not everyone of these patients will want gene therapy; not everyone can afford it.

By afford it, I mean have insurance cover it, which is the final piece of the pricing puzzle. Who will pay the $3.5 million per patient? State Medicaid plans? Commercial insurance? What if a patient on Blue Cross Blue Shield is approved, gets the gene therapy, has it reimbursed, but the following year switches plans? How does this benefit the bottom line at BCBS? Will insurance companies say no to gene therapy based on these concerns?

Advocacy is Key

This is where our decades of strong advocacy in the hemophilia community will make a difference. In a way, we’ve been preparing for this moment our whole lives. While the new drugs are not being touted as a cure, those of us old enough remember the slogan “A Cure by 2000!” We have fought for compensation for those infected by HIV and hepatitis from unsafe blood products. We fought for the new recombinant drugs, when insurance denied us. We fought for longer half-life drugs, for prophy, for bi-specific antibody products. All of these came with higher price tags, and eventually we prevailed.

And now?

We will all need to be educated about this new gene therapy, and how to approach our insurance companies, if we want it. As we have been preaching since 2005, when everything changed in insurance for hemophilia, you need to learn to speak the insurance company’s language; debate with them in a way they are used to; work with your healthcare team; stand with your state hemophilia group.

There are so many excellent products available to treat hemophilia, will insurance companies use this to deny gene therapy? At this point, no one knows, but we do know we need to get prepared. Why?

BioMarin is actively working on getting Rotavian approved for hemophilia A in the US. And that will impact thousands more in our community. How the insurance reimbursement of Hemgenix plays out could be a harbinger of things to come.

Read CSL Behring’s press release here.

Hemophilia Gene Therapy—is the US Next?

Laurie Kelley November 20, 2022

Paul Clement

Last week we discussed Roctavian, the brand name of BioMarin Pharmaceutical’s gene therapy product, valoctocogene roxaparvovec, to treat patients with severe hemophilia A, and the European Commission’s August 24, 2022, conditional marketing authorization for the therapy. Two big questions on everyone’s mind are: when will it be approved in the US and what will it cost?

US Approval Soon?

BioMarin submitted a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) for approval to market Roctavian back in 2019. In August 2020, the FDA responded by issuing a Complete Response Letter (CRL) to BioMarin, delaying their approval request and requiring two more years of additional safety and efficacy data from the company’s Phase 3 GENEr8-1 clinical trial.

Why did the FDA delay approval of BioMarin’s gene therapy? Its primary concern was the trend in clinical trial data showing decreasing efficacy of Roctavian over time, which could potentially render the therapy ineffective after several years.

At the end of September, BioMarin resubmitted its BLA for Roctavian with the requested additional data, and in a press release, announced that the FDA had accepted its resubmission of the BLA on October 12, 2022. Similar to the therapy’s conditional approval in Europe, the BLA resubmission includes a proposed long-term extension study to follow all trial participants for up to 15 years, plus two post-approval registry studies to follow patients dosed in a real-world setting.

According to BioMarin, BLA resubmissions are typically are followed by a six-month review process. However, the company anticipates that an additional three months of review may be necessary to review the new data—bringing the approval date to sometime in mid-2023. The approval of Roctavian is likely to proceed fairly rapidly: the FDA had previously granted Roctavian Breakthrough Therapy as well as Regenerative Medicine Advanced Therapy designations, both FDA programs designed to speed up the development and review process of therapies. And Roctavian also received an orphan drug designation from the FDA, granting it seven years of market exclusivity after approval. If approved, Roctavian would be the first commercially-available gene therapy in the U.S. for the treatment of severe hemophilia A.

How Much Will It Cost?

This is the million dollar question. Cell and gene therapies are extraordinarily expensive, ranging in cost from $373,000 (Yescarta, a cell therapy for lymphoma) to $2.8 million (Zynteglo, a cell therapy for beta-thalassemia). Pharmaceutical companies would like a one-time payment for the therapy up front, but health insurance companies balk at the high cost, citing concerns about efficacy (what if it does not work?), durability (how long will it last?) and patient mobility (why should we pay for a therapy that may last a lifetime, when the patient is likely to have a policy with us only three to six years?).

In response to these concerns and “failure to launch” for several gene therapies in Europe due to their high cost, pharmaceutical and health insurance companies have been exploring 16 different reimbursement models to make these expensive therapies more palatable to both parties. Two models stand out: the annuity model in which insurers make payments in installments over time; and the outcomes/milestone-based contract model in which the payment amount is adjusted depending on whether a pre-specified health outcome is achieved (i.e., the patient’s factor level will remain above a certain level for a certain number of years) if the outcome is not met, the pharmaceutical company might provide large rebates for patients that fail to respond to a therapy in a predetermined way). Both of these payment models may also be combined, in which an outcome-based contract with the manufacturer is connected to an annuity payment for the therapy, contingent on a positive health outcome.

BioMarin expects Roctavian’s list price in Europe to be roughly $1.5 million, after all discounts. They are currently in payment negotiations with Germany and will then move to France, Italy, and Spain, and then to other countries. (The healthcare systems in France, Germany, Italy, Spain and England are predominantly single-payer systems, with public health insurance covering either the entire, or the vast majority of the population, making payment negotiations easier than in the highly fragmented health insurance industry in the US). In Europe, BioMarin is negotiating outcomes-based agreements, with the goal of guarding against the risk of a “non-response” to treatment for at least five to eight years.

What about the cost in the US? BioMarin has not set a price for Roctavian in the US, but has suggested it will be between $2 and $3 million. How this new therapy will be greeted by health insurance industry in the US remains to be seen. So far, the effect of cell and gene therapies on the US health insurance landscape has been minimal, because there are currently only a handful of products licensed in the US. However, major changes are on the horizon: there are about 3,000 cell and gene therapy therapies in the pipeline, and by 2025, the FDA predicts they will be approving between 10 and 20 cell and gene therapy products per year. And these therapies will require the adoption of new payment models if they are to reach  consumers.

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