Dr Guy Young
Monthly subcutaneous prophylaxis with the small interference RNA (siRNA) therapeutic fitusiran can significantly reduce bleeding in people with haemophilia A or B.
Speaking in a plenary scientific session at ASH 2021, Dr Guy Young said that patients with inhibitors typically do poorly compared to other people with haemophilia.
Dr Young, director of the Haemostasis and Thrombosis Centre at the Children’s Hospital Los Angeles, said patients with inhibitors lost more days from work or school, and were more likely to use walking aids or a wheelchair.
As well, their mortality was 1.7 times higher than people with haemophilia without inhibitors.
Dr Young said there was also a huge treatment burden associated with frequent IV infusions, especially in children.
The open-label, international phase 3 study in 57 males from 12 years of age randomised patients with inhibitors to on-demand use of bypassing agents with or without monthly 80 mg subcutaneous fitusiran prophylaxis for an initial treatment period after nine months.
The ATLAS-INH study found the observed median annualised bleeding rate (ABR) was 16.8 for patients treated only with on-demand bypassing agents compared to 0 for fitusiran-treated patients.
“I would comment that this is not just a statistically important or statistically significant endpoint but it’s definitely a clinically meaningful and important endpoint as well,” he said.
Similarly the median observed ABR for treated spontaneous bleeds was 13.4 with bypassing agents versus 0 with fitusiran and for treated joint bleeds was 11.7 versus 0 respectively.
Dr Young said quality of life, as measured by Haem-A-QoL questionnaire, also improved for patients on fitusiran.
Treatment-emergent adverse events of special interest included elevations of transaminases (0% with bypassing agents only versus 12.2% with fitusiran) and two patients receiving fitusiran experiencing a suspected or confirmed thromboembolic event.
Only one patient in the fitusiran group was discontinued from the study due to an adverse event.
Dr Young said fitusiran lowered antithrombin levels to about 10-20% of normal levels – which effectively rebalanced haemostasis in patients with haemophilia.
Dr Steven Pipe told the meeting that the ATLAS-A/B study of on-demand factor concentrates for breakthrough bleeding plus or minus fitusiran prophylaxis in patients with haemophilia and without inhibitors had similar results.
The observed median ABR for all treated bleeds was 21.8 in the on-demand treatment group compared to 0 with fitusiran prophylaxis and 15.9 versus 0 for treated joint bleeds.
“I think this is a tremendous leap forward in the therapy we can bring to this community,” he said in the press meeting for late-breaking abstracts.
“Based on some of the current dosing schedules that are currently being evaluated with fitusiran, it is possible to achieve effective prophylaxis with as little as six subcutaneous injections over the course of a year.”
Both studies, which included sites in Australia, were funded by Sanofi Genzyme.