Pharma, BioPharma, Legal

Sanofi’s FDA Nod in Hemophilia Gives Patients More Convenience, Brings Roche New Competition

FDA approval of Sanofi hemophilia A drug Altuviiio provides patients with a therapeutic option that lasts longer than most other products available, including one already marketed by the French pharma giant. Altuviiio also gives Sanofi a way to better compete against blockbuster Roche drug Hemlibra.

Hemophilia A patients manage the chronic disorder with infusions administered as frequently as every two to three days. The FDA has approved a Sanofi drug designed to last longer in the body, giving patients a new option that’s dosed once a week.

The regulatory decision announced Thursday covers both adults and children who may use the new Sanofi drug for preventing bleeding as well as for on-demand treatment of bleeding episodes. The drug, known in development as efanesoctocog alfa, will be marketed under the name “Altuviiio.”

Coagulation is a process. Tissue injury activates a series of proteins, or clotting factors, each one playing a role in the coagulation cascade that culminates in a blood clot. In hemophilia A, genetic mutations lead to low levels of a clotting protein called factor VIII. Without enough factor VIII, patients are susceptible to excessive bleeding or spontaneous bleeding into their joints that leads to joint damage and chronic pain.

Hemophilia A can be treated with factor concentrates, infusions of the deficient clotting protein that are either derived from human plasma or engineered in a lab. But factor concentrates don’t last long in the body, so patients need infusions of these treatments every two to three days. Sanofi is already in the hemophilia A market with Eloctate, a long-acting engineered version of factor VIII that’s dosed every three to five days.

Altuviiio is a fusion protein that combines an engineered version of factor VIII with part of von Willebrand factor, another protein that’s part of the clotting cascade. Von Willebrand factor helps platelets stick together and in Altuviiio, this protein stabilizes the engineered factor VIII protein, said Dietmar Berger, Sanofi’s chief medical officer and global head of development, speaking in an interview in advance of Altuviiio’s approval. But the short half-life of von Willebrand factor means a therapy employing this protein won’t last long, a limitation called the von Willebrand factor ceiling. Altuviiio breaks through this ceiling by adding another component: polypeptide chains attached to the sides of the molecule. By shielding the molecule from enzymes in the body that break it down, these chains enable Altuviiio to last as long as a week, Berger said.

“First the side chains come off, then von Willebrand factor,” Berger said. “Then factor VIII does its job. It just stays in the circulation much longer.”

Altuviiio came to Sanofi via the pharma giant’s $11.6 billion acquisition of Bioverativ in 2018. That company was already working with technology from Amunix that extends the length of time a biological therapy lasts in circulation. In Altuviiio, this Amunix technology is used for both the von Willebrand factor and peptide chain components of the drug, Berger said. A year ago, Sanofi acquired Amunix in a $1 billion deal that was focused mainly on the applications of the biotech’s technology in cancer drugs.

While levels of all infused factor VIII proteins decline over time, Berger said the design of the Altuviiio molecule results in a slower decline that keeps a patient in a protected range for a longer period. The therapy’s efficacy was assessed in an open-label Phase 3 clinical trial that enrolled 159 participants who have severe hemophilia A. The 133 patients in the prophylaxis arm received an intravenous injection of Altuviiio once a week for 52 weeks. On-demand treatment was assessed in a group of 26 patients. These participants received on-demand treatment with the study drug for 26 weeks, then switched to once-weekly dosing for another 26 weeks.

The study’s main goal was to measure annualized bleeding rates. On this mark, results showed an average annualized bleeding rate of 0.70. One key secondary goal compared the annualized bleeding rate of patients in the study to the rates these patients experienced previously while receiving standard factor VIII treatments. On this comparison, Altuviiio led to a 77% reduction in annualized bleeding rate. The trial results also showed reductions in joint bleeding.

The Sanofi therapy was well tolerated by patients in the study. One problem for factor VIII therapy is that patients can develop antibodies that neutralize the infused proteins. Altuviiio’s label notes that neutralizing antibodies were not observed in clinical trials, but if patients do not achieve expected factor VIII levels or bleeding is not controlled, tests should be done to measure blood concentrations of these antibodies. Data from the pivotal study were published last month in the New England Journal of Medicine.

Hemophilia A patients already have a drug alternative that offers less frequent dosing. Blockbuster Roche product Hemlibra is a bispecific antibody that mimics the function of factor VIII, enabling the coagulation cascade to continue. That drug, dosed as a subcutaneous injection once weekly, every two weeks, or once a month, accounted for 2022 revenue of 3.8 billion Swiss francs (about $4 billion), a 27% increase over 2021 sales, according to Roche’s most recent financial report.

As Hemlibra’s revenue grows, Eloctate sales have fallen. Sanofi reported €580 million in Eloctate sales in 2022, a 5.9% decline from the prior year. Berger said the hemophilia A market is served by many therapies, spanning factor products such as Eloctate and non-factor products like Hemlibra. He added that Sanofi believes Altuviiio will become the dominant product in the factor VIII market. Some patients may switch from Eloctate to Altuviiio, and Sanofi aims to capture patients from the non-factor market as well, he said.

Sanofi said it will disclose Altuviiio’s price when the drug becomes commercially available. The company anticipates an April drug launch. Sanofi developed Altuviiio in partnership with Swedish Orphan Biovitrum (Sobi), also its partner on the commercialization of Eloctate and hemophilia B drug Alprolix. For Altuviiio, Sobi has rights to commercialize the drug in Europe, North Africa, Russia, and most of the Middle East. Sanofi holds commercialization rights in the rest of the world. An application seeking European marketing authorization is being readied for potential submission in the second half of this year.

Photo: Nathan Laine/Bloomberg, via Getty Images

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