Antithrombin Gamma (Genetical Recombination)

Two fitusiran Phase 3 studies published in The Lancet and The Lancet Haematology highlight potential to address unmet needs across all types of hemophilia Both Phase 3 studies achieved their primary and secondary endpoints; fitusiran prophylaxis demonstrated significant and clinically meaningful improvements in bleed protection across all hemophilia populations, presented at ASH 2021 Paris– April 4, 2023– Two studies, published in The Lancet and The Lancet Haematology, evaluating the efficacy and safety of fitusiran, an investigational siRNA therapy for the prophylactic treatment of adults and adolescents with hemophilia A or B, reinforce the potential of this investigational therapy to transform the current standard of care and address unmet needs for all types of hemophilia, regardless of inhibitor status. Hemophilia A and B are rare congenital lifelong bleeding disorders in which the ability of a person’s blood to clot is impaired, leading to excessive bleeds and spontaneous bleeds into joints that can result in joint damage and chronic pain, and significantly impact quality of life. Fitusiran has the potential to provide prophylaxis for all types of hemophilia, regardless of inhibitor status, with as few as six subcutaneous injections per year. Dietmar Berger, M.D., Ph.D. Head of Global R&D ad interim and Chief Medical Officer at Sanofi “Sanofi is committed to advancing the standard of care for all people with hemophiliathrough innovative science,providing consistent bleed protection while reducing treatment burden. We are entering a new erainhemophilia where, for the first time, people can choose therapies that meet their personal needs.These published data validateour science and add to a growing body of evidence supporting fitusiran’s potential to transform the treatment landscape. We look forward to sharing additional data on fitusiranlater this year.” Both Phase 3 studies compared once-monthly subcutaneous fitusiran prophylaxis (80mg) with on-demand/episodic use of clotting factor concentrates in the ATLAS-A/B study, and on-demand/episodic use of bypassing agents in the ATLAS-INH study. Across both clinical studies, prophylactic treatment with fitusiran reduced annualized bleeding rates by 90% (95% CI [84.1%; 93.6%], P <0.0001) compared to the control arms, showing a statistically significant and clinically meaningful improvement in bleeding episodes when compared to on-demand treatments; and showed improvement in quality of life. In the study ATLAS-INH study published by The Lancet, 66% of participants with inhibitors (25 out of 38) receiving fitusiran 80mg monthly experienced zero bleeding episodes compared to 5% (1 out of 19) receiving an on-demand bypassing agent after nine months of treatment. The ATLAS A/B study published in The Lancet Haematology showed 51% of participants without inhibitors (40 out of 79) who received fitusiran 80mg monthly prophylaxis experienced zero bleeds compared to 5% (2 out of 40) in the comparator group, receiving on-demand clotting factor concentrates. Sanofi is currently investigating the efficacy and safety of fitusiran under a revised regimen which includes lower doses and less frequent dosing (as few as six subcutaneous injections per year), maintaining an antithrombin target range of 15-35% in all ongoing studies. ATLAS-AB Phase 3 Study ATLAS-A/B is a Phase 3 randomized, open-label study investigating the efficacy and safety of fitusiran in males ≥12 years with severe hemophilia A or B without inhibitors who had previously been treated with on-demand clotting factor concentrates. Study participants (n=120) were randomized 2:1 to receive either once-monthly 80mg subcutaneous fitusiran prophylaxis or on-demand clotting factor concentrates. The primary endpoint is annualized bleeding rate. ATLAS-INH Phase 3 Study The ATLAS-INH study is a randomized, open-label Phase 3 study designed to evaluate the safety and efficacy of fitusiran in males ≥12 years with severe hemophilia A or B with inhibitors to factor VIII or IX. Study participants (n=57) receiving on-demand treatment with bypassing agents (BPA) were randomized in a 2:1 ratio to receive once-monthly 80mg subcutaneous fitusiran prophylaxis or continue with on-demand BPA. The primary endpoint is annualized bleeding rate. About fitusiran Fitusiran is an investigational, subcutaneously administered small interference RNA therapeutic in development for the prophylactic treatment of people with hemophilia A or B, with or without inhibitors. Fitusiran is designed to lower antithrombin, a protein that inhibits blood clotting, with the goal of promoting thrombin generation to rebalance hemostasis and prevent bleeds. Fitusiran utilizes Alnylam Pharmaceutical Inc.’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. Fitusiran is currently under clinical investigation and has not been evaluated by any regulatory authority. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY. 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FRIDAY, March 31, 2023 -- An experimental injectable drug appears effective in reducing bleeds in patients with hemophilia A and B, according to a pair of new clinical trials. Two-thirds of people with treatment-resistant hemophilia who were treated with the drug fitusiran had no bleeds at all after nine months, versus just 5% of people treated with drugs that enhance clotting, according to a trial published online March 29 in The Lancet . Fitusiran also outperformed other drugs in a second trial that involved people with hemophilia. In that trial, 51% of patients experienced no bleeds compared to 5% of the control group. That report appears in The Lancet Hematology . The drug is the first treatment that can be given in advance to prevent bleeds in people with both types of hemophilia, regardless of whether their disease is resistant to treatment, the researchers reported. Hemophilia is an inherited bleeding disorder. People with hemophilia A or B are missing natural proteins that help form blood clots to stop bleeding. Without those proteins, these patients bleed spontaneously into their joints and muscles, and can take much longer to stop bleeding after an injury. Fitusiran is a type of drug called a small interfering RNA therapy. These drugs work by interfering with the production of specific proteins in the body. Fitusiran targets antithrombin, a protein that reduces blood clotting. As a result, patients are better able to form clots that stop dangerous bleeding. The drug is delivered via a monthly injection. The first clinical trial was conducted at 26 hospitals in 12 countries. It included 56 male patients, aged 12 and older, with severe treatment-resistant hemophilia. Two-thirds were treated with fitusiran, while the others (the "control" group) were given drugs that enhance clotting as needed. The average annual bleeding rate among fitusiran patients was 0, compared to nearly 17 bleeds on average in the control group. “The data is encouraging and suggests it may be the first prophylactic treatment — meaning it can be given to prevent bleeds rather than to treat them after they have already occurred — that works for both hemophilia A and B patients with inhibitors (treatment resistance),” lead researcher Guy Young said in a journal news release. “Hemophilia B patients’ treatment options are currently limited to on-demand treatments, which treat bleeds after they have occurred,” added Young, a professor at the University of Southern California Keck School of Medicine, in Los Angeles. The second trial involved 45 hospitals in 17 countries, with 120 male patients, aged 12 or older, who had hemophilia but no treatment resistance. Again, two-thirds were treated with monthly fitusiran, while the others were given clotting drugs on demand. The average annual bleeding rate among fitusiran patients in this study was 0, compared to nearly 22 bleeds on average in the control group. The main side effect in both studies was an increase in levels of alanine aminotransferase, an enzyme released into the blood when the liver is damaged. About 32% of fitusiran patients experienced an increase in this enzyme in the first trial, and 23% in the second trial. No deaths were reported in either trial. “Our study looks at the use of fitusiran in patients with hemophilia A or B without inhibitors and complements the findings from the study looking at fitusiran with inhibitors, also finding that it is very effective in preventing bleeds,” said lead researcher Alok Srivastava of Christian Medical College in Vellore, India. “Fitusiran is administered by under-the-skin injections, which can be easily taken at home. With this drug being administered just once a month or even less frequently, there is marked reduction of treatment burden,” Srivastava continued. “This means patients with hemophilia could manage their condition with fewer trips to [the] hospital, which can cause worry and be disruptive to daily life. This would lead to an improved quality of life as documented in the study.” Both clinical trials were funded by Sanofi, the pharmaceutical company that created fitusiran. Sources The Lancet , news release, March 29, 2023 Posted March 2023