Sanofi's hemophilia drug, put on pause last year, could be closer to the FDA's doorstep on new late-stage data that shows the treatment significantly reduced bleeds. But the adverse events that raised red flags are still persisting in one study.
The French Big Pharma posted data on two phase 3 trials of the small interference RNA treatment, dubbed fitusiran, as a preventative treatment. All studies of the drug were paused last November on concerns about thrombotic events.
The first late-stage study, ATLAS-A/B, tested fitusiran in patients with severe hemophilia A or B without inhibitors who previously underwent on-demand factor therapy. The treatment reduced the annualized bleeding rate by 89.9% compared to on-demand factor therapy for bleeding episodes.
That means the drug met the primary goal of the trial with a significantly and clinically meaningful reduction in annualized bleeding rate, Sanofi said Tuesday at the American Society of Hematology meeting in Atlanta that runs from Dec. 11 to 14. The company said that 50.6% of patients, or 40 people, who received the drug had zero treated bleeds compared to 5% of patients in the on-demand arm.
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There were no cases of thromboembolism reported in the study. The most common adverse events included increased levels of alanine aminotransferase, or ALT, and upper respiratory tract infection.
The second phase 3 trial, ATLAS-INH, looked at the drug in patients with severe hemophilia A or B with inhibitors to factor VIII or IX. Similar to the other trial, the drug reduced the treated annualized bleeding rate by 90.8% compared to patients treated with on-demand bypassing agents, or BPAs. Fitusiran led to zero treated bleeds in 65.8% of patients on fitusiran versus 5.3% of patients in the BPA arm.
But this trial saw the recurrence of adverse events, with 24.4% of patients experiencing ALT or aspartate aminotransferase (AST) elevation more than 3x the upper limit. Suspected or confirmed cases of thromboembolism, or blood clotting, was also found in two patients. The company characterized the treatment emergent adverse events as "generally consistent with previously identified risks" of the drug or ones associated with the bleeding disorder.
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Sanofi paused development of the drug last November after side effects were found, including thrombotic events. The company resumed studies months later and has updated its plan to now test the treatment at 50 mg every other month instead of 80 mg. In the two phase 3 trials reading out today, fitusiran was injected under the skin once a month at 80 mg.
The revised dosing and treatment schedule led Sanofi to push back its potential drug approval application to 2024, which is 18 months behind its original plan.
The FDA placed a clinical hold on fitusiran in 2017 after a patient with hemophilia A died from a blood clot in a phase 2 study. Sanofi subsequently obtained worldwide rights to the candidate from Alnylam in January 2018. Alnylam stands to gain tiered royalties of up to 30% on global sales of the drug, if approved.