BioMarin: Roctavian for Hem A likely to patients by end of summer

Availability of $2.9M gene therapy expected 2 months after its approval

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The approval by the U.S. Food and Drug Administration (FDA) of BioMarin Pharmaceutical’s Roctavian (valoctocogene roxaparvovec-rvox) late last month means that eligible adults with severe hemophilia A will soon have access to a gene therapy for the first time.

“Adults with severe hemophilia A live with several limitations, including … a high risk of health complications,” Hank Fuchs, MD, president of worldwide research and development at BioMarin, said in a written Q&A with Hemophilia News Today.

“As a one-time, single-dose treatment, Roctavian has the potential to transform care for eligible adults with severe hemophilia A,” Fuchs said.

Roctavian is now being manufactured at a site in California that is “one of the largest gene therapy manufacturing facilities of its kind,” according to Fuchs. The therapy will become commercially available at the end of August — two months following its approval in the U.S.

“Because there are several steps required from the time a patient expresses interest until that person receives treatment with Roctavian, we anticipate that is the earliest we’d begin to see patients being treated commercially,” Fuchs said.

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Hem A Gene Therapy Roctavian More Cost-effective Than Hemlibra

One-time Roctavian treatment expected to replace prophylaxis

Roctavian works to supply hemophilia A patients with a functional version of the F8 gene via a single, into-the-vein (intravenous) infusion. Mutations in this gene cause hemophilia A patients to lack factor VIII, known as FVIII, a key blood clotting protein.

By giving patients a healthy version of the gene encoding FVIII, Roctavian “addresses the underlying root cause of hemophilia, enabling people with severe hemophilia A to produce their own FVIII,” Fuchs explained.

Typically, hemophilia A patients rely on regular infusions of FVIII replacement therapy or other prophylactic treatments to prevent bleeds.

“We know that many patients have difficulty keeping up with the burden of chronic therapy,” Fuchs noted. For these patients, the one-time gene therapy offers “the possibility of freedom from years of prophylaxis [preventive treatment] that can require weekly injections or infusions.”

Still, gene therapies come with a high price, and are considered to be among the most expensive medical treatments in the world.

Roctavian’s list price will be $2.9 million, based on the weight of a typical patient, according to Andrew Villani, executive director of product communications and media at BioMarin.

For reference, Hemgenix, a gene therapy for hemophilia B that was approved in the U.S. in November 2022, and granted approval in Europe in February, has a list price of about $3.5 million.

But in light of the fact that Roctavian only requires a one-time infusion and appears highly effective, the gene therapy still “brings value to individuals and healthcare systems,” Villani said.

We set a price that both captures the value of Roctavian and results in material savings to the healthcare system.

To give perspective, Villani noted that standard-of-care hemophilia treatment costs about $800,000 per year for a typical patient. That means that in about four years, the cost of routine preventive therapy already exceeds the one-time cost of Roctavian.

“We set a price that both captures the value of Roctavian and results in material savings to the healthcare system,” Villani said.

Given its cost, some insurance companies might be hesitant to offer overage. To generate confidence from insurance companies in Roctavian’s value, BioMarin is offering an outcomes-based warranty to both public and private insurers.

That means that the company would reimburse insurers by up to 100% should a patient fail to respond to the gene therapy or stop responding to it in the first four years following dosing.

BioMarin believes such a program “will help enable the greatest number of eligible patients to receive treatment,” according to Villani. “We have been working with payers to educate them on the clinical and economic value to help drive coverage as soon as possible following launch. ”

Patients looking for additional support on accessing Roctavian can reach out to BioMarin Rare Connections for more information.

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Hem A gene therapy 1st to be approved in US

Roctavian’s approval in the U.S. had been years in the making. BioMarin first applied for clearance of the gene therapy about 3.5 years ago, based on three-year data from a Phase 1/2 dose escalation study (NCT02576795). That application also included six-month interim findings from the ongoing pivotal Phase 3 GENEr8-1 trial (NCT03370913), which is slated to run through November 2024. GENEr8-1 enrolled 134 men with severe hemophilia A on routine preventive treatment.

Upon the FDA’s request, BioMarin resubmitted the application with two-year findings from GENEr8-1 in 2022, prompting the agency to additionally request three-year data. That data, which became available this year, backed the FDA’s eventual approval of Roctavian last month.

Three-year data showed that participants had an 82.9% reduction in bleeds that required treatment compared with the period before the trial. Most participants had not experienced any clinically relevant bleeds, and 92% were able to stop using preventive treatments, the data showed.

FVIII activity remained high, and patients were able to lower their use of FVIII replacement therapy by 96.8%.

“Most study participants continued to respond to treatment through year three and beyond, without supplemental use of regular prophylaxis,” Fuchs said.

To best understand why those findings are meaningful, “it’s important first to acknowledge how devastating untreated hemophilia is and what patients were up against,” Fuchs said.

According to Fuchs, when left untreated, hemophilia patients will bleed without cause about 30-60 times per year. In the long term, bleeds can lead to joint damage and immobility, or become life-threatening.

“For patients that live with this disease on a daily basis, a treatment like Roctavian may address significant unmet needs … by way of fewer bleeds, without the burden of chronic therapies,” Fuchs said, adding, “Our hope is that these people can live life more fully and engage in activities they enjoy, like traveling or spending time with their family.”

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Patients given gene therapy will be followed for up to 15 years

While it’s not known for certain whether the treatment’s effects will wane over time, patients in the Phase 1/2 trial have now been followed for more than six years.

Findings to date indicate that most patients are still off preventive therapy, which “may provide insight into the longevity of response,” Fuchs noted.

To learn more about Roctavian’s effects over the long term, GENEr8-1 participants will continue to be monitored for up to 15 years. A post-approval, real-world study will similarly follow patients for 15 years or more.

A number of other clinical studies also are ongoing to evaluate the potential use of Roctavian across different patient populations.

Specifically, two Phase 1/2 trials are underway to investigate Roctavian’s safety and effectiveness in patients who have antibodies against AAV5, the therapy’s viral carrier (NCT03520712), or who have neutralizing antibodies, or inhibitors, against FVIII (NCT04684940).

The presence of these antibodies could potentially compromise the therapy’s effectiveness. Hemophilia A patients who have these inhibitors were not included in GENEr8-1 and thus are not now eligible to receive treatment with Roctavian. All patients are screened for these antibodies prior to being given the infusion.

Patients also must be screened for liver health prior to receiving the gene therapy. Most patients in GENEr8-1 required the use of corticosteroids to combat elevations in certain liver enzymes that were observed after they received treatment. Individuals with pre-existing liver problems will need to consult a specialist to see if they are eligible to receive Roctavian.

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BioMarin looking to expand access to Roctavian

Another open-label Phase 3b trial, called GENEr8-3 (NCT04323098), is investigating the use of Roctavian when given alongside anti-inflammatory corticosteroids.

According to Fuchs, BioMarin will provide data for these studies as it becomes available, “building on what already constitutes the largest clinical data package for gene therapy in hemophilia.”

“We look forward to sharing the findings of these studies and their implications on Roctavian’s eligibility population,” Fuchs said, but noted that it is too soon to speculate as to whether these studies will affect regulatory decisions about who is eligible to receive the hem A gene therapy.

Roctavian has earned conditional approval in the European Union for adults with severe hemophilia A who do not have antibodies against AAV5 or FVIII inhibitors. Conditional approval means that while the company can market a therapy, more data are still required by regulatory authorities to confirm its clinical benefits.

The conditional approval, granted last year, was based largely on two-year data from the GENEr8-1 trial, as well as six-year data from the Phase 1/2 trial.

According to Fuchs, conversion to a full approval “will be contingent on the provision of additional data from currently ongoing Roctavian clinical studies, including longer-term follow up of patients enrolled in the pivotal trial GENEr8-1.”

“We are continuing to engage with regulatory agencies around the world with the goal of expanding access to Roctavian,” Fuchs said.

“On behalf of all of us at BioMarin, I would like to thank the community — individuals living with hemophilia, as well as their caregivers and the healthcare providers whose contributions led to the development and approval of Roctavian,” he said.