A one-time BioMarin Pharmaceutical treatment that fixes the problem at the root of hemophilia A has finally won FDA approval, making it the first gene therapy authorized for the inherited bleeding disorder.
The Thursday regulatory decision for the gene therapy, Roctavian, covers adults with severe hemophilia A. BioMarin set a $2.9 million wholesale price for the product. But the San Rafael, California-based drugmaker is also giving the hemophilia community and insurance companies assurances that the gene therapy will work. BioMarin is offering a warranty program that will pay back the therapy’s price if a patient’s disease does not respond to the treatment.
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In hemophilia A, patients have an inherited deficiency of factor VIII, a clotting protein. This deficiency makes patients more susceptible to painful bleeding episodes that can happen spontaneously. Standard treatment includes regular infusions of engineered versions of the factor VIII protein that patients lack, which are intended to prevent these episodes. Another option is Hemlibra, a Roche antibody drug that mimics the function of the deficient clotting protein.
Roctavian consists of a functioning version of the gene that provides instructions for making factor VIII. Administered as an intravenous infusion, the gene therapy reaches a patient’s cells aboard an engineered virus called adeno-associated virus serotype 5. FDA approval of Roctavian covers patients who don’t have pre-existing antibodies to this virus that would render the therapy ineffective. Patients who meet this eligibility requirement are identified with a companion diagnostic that was also approved by the FDA on Thursday. By BioMarin’s count, about 6,500 adults in the U.S. have severe hemophilia A. Of those, the company estimates 2,500 are eligible for Roctavian under the current approval.
The Roctavian regulatory decision comes nearly three years after the FDA rejected the gene therapy, citing data discrepancies between Phase 1/2 testing and the pivotal Phase 3 study. The company continued to follow patients in the study to accrue more data. Approval of Roctavian is based on the results of a Phase 3 study that has more than three years of patient data. Of 134 patients who received the gene therapy, 112 had annualized bleeding rate data collected for six months prior to receiving Roctavian. During this period, they received factor VIII therapies. The remaining 22 patients had their baseline data collected retrospectively.
The trial results showed that following dosing with Roctavian, patients’ annualized bleeding rate dropped to 2.6 episodes per year, a 52% decline from baseline. In addition, patients also reported a reduction in the rate of spontaneous bleeds and joint bleeds compared to baseline. The most common adverse reactions included nausea, fatigue, and headache. But laboratory testing also showed higher levels of liver enzymes, which can be a sign of toxic effects on the liver. This problem can be addressed with corticosteroids. The drug’s label tells physicians to monitor a patient’s liver enzymes weekly for at least 26 weeks after dosing, and to monitor and manage for the any adverse effects associated with corticosteroid treatment.
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Earlier this week, during the annual meeting of the International Society on Thrombosis and Haemostasis, BioMarin presented three-year data showing that participants in the Phase 3 study had an 82.9% reduction in treated bleeds overall compared with baseline. The study also found the gene therapy led to a 96.8% reduction in factor VIII usage overall compared with baseline.
“Spontaneous bleeds and joint bleeds are medically important events that define severe hemophilia A as a bad condition, and the fact that those are dramatically affected by Roctavian is Roctavian’s superpower,” Hank Fuchs, BioMarin’s president of worldwide research & development said, speaking during a conference call Thursday.
The European Commission granted Roctavian conditional marketing authorization last August, based on two-year clinical trial data. While Roctavian is the first gene therapy approved for hemophilia A, it is not the first hemophilia gene therapy. Last November, the FDA approved Hemgenix, a CSL Behring gene therapy for the rare hemophilia B. Hemgenix carries a $3.5 million price, but CSL Behring has pledged to offer value-based agreements to commercial payers. These agreements tie the reimbursement of a therapy to predetermined outcomes that show the treatment worked.
Under the warranty for Roctavian, BioMarin will reimburse up to 100% of the therapy’s wholesale acquisition cost for those who don’t respond to the therapy. BioMarin Chief Commercial Officer Jeff Ajer said this four-year warranty will be offered to all U.S. insurers, both public and private. If a treated patient loses response to the therapy within the four-year period, Ajer said BioMarin will reimburse payers on a prorated basis. But he added that continued benefit beyond four years represents savings to the healthcare system.
Ajer said Roctavian will become commercially available in the U.S. in about two months. But prior to receiving the therapy, patients will need to go through several steps that include determining if their insurance will cover the therapy, taking the test to determine eligibility for the treatment, and testing to establish a baseline for liver enzyme levels. Patients should expect that the various steps will take anywhere from two to five months, Ajer said.
Public domain image by Flickr user SciTechTrend
