Two novel treatment options for haemophilia had promising results reported at the ISTH 2022 ‘late-breaking’ session in London.

A preliminary analysis of Phase III data for the anti-tissue factor pathway inhibitor (TFPI) antibody concizumab in patients with haemophilia A or B with inhibitors showed an impressive reduction in treated bleeds.

Presenting a first look at data from the explorer7 study, trial investigators from Spain said there was an 86% reduction in spontaneous and traumatic bleeds in patients taking concizumab prophylaxis, with an estimated mean annualised bleeding rate (ABR) of 1.7 versus 11.8 in the control group.

Other results showed an overall median ABR for the drug of zero, compared to 9.8 for no prophylaxis, and that 64% versus 11%, respectively, experienced no treated bleeds.

In terms of the trials secondary objective – quality of life – a positive trend observed in all others domain of the scale SR36v2, but the difference was not significant between the trial arms for bodily pain and physical function, the secondary endpoints, the meeting heard.

The drug also appeared to have to be safe and well-tolerated; while there was one thromboembolic event with concizumab treatment, it was resolved and did not re-emerge after treatment was restarted, and most adverse events were considered mild, he said.

According to Dr Víctor Jiménez-Yuste, Head of the Haematology Department at the Hospital Universitario La Paz in Madrid, the results of explorer 7 indicate that “there is a potential for concizumab to become a new treatment option for people living with haemophilia A or B with inhibitors.”

The drug’s developer Novo Nordisk confirmed that it plans to submit concizumab for regulatory approval as a once-daily subcutaneous prophylactic treatment of haemophilia A or B with inhibitors in the EU and UK next year.

The study was funded by Novo Nordisk.

Fitusiran cuts bleeds by 61%, but with safety considerations

At the same late breaking session,  findings were presented from the Phase III ATLAS-PPX study which estimated that the small interference RNA therapy fitusiran (Sanofi) can cut the ABR by 61% in patients with haemophilia A or B with or without inhibitors.

The trial assessed the efficacy and safety of once-monthly, sub-cutaneous fitusiran (80mg) in male adults and adolescents with severe haemophilia A or B, who were previously treated with prior factor or bypassing agent (BPA) prophylaxis.

Professor Gili Kenet, trial investigator and head of the Amalia Biron Thrombosis Research Institute of Tel Aviv University, noted that patients selected for the study were already “very well controlled, young patients adherent to prophylaxis”, but that following treatment with fitusiran the median ABR dropped from 4.4% to zero.

The data also showed that 63% of adults and adolescents treated with fitusiran experienced zero treated bleeds compared to 17% with prior factor or BPA prophylaxis, she said. “And if we look at the number of patients that had less than three bleeds per year – [the figure] then increased from 63% to 89%, [which is] quite remarkable,” she added.

According to the findings, fitusiran also resulted in a better physical health score and a significantly improved total Haem – A – QoL score, showing a “statistically significant improvement in health related quality of life”.

Safety findings

With regard to safety, the findings were consistent with the previously identified risk profile fitusiran, with suspected or confirmed thromboembolic events reported in 2 participants (3.0%) – a confirmed cerebrovascular event in a patient with a  previous (undisclosed) history of DVT, and a suspected thrombosis of the papilla of the eye.

However, “the company realised that [these thromboembolic events] occurred when the antithrombin level was extremely low, below 15%, and therefore the dosing regimen was modified to minimise and mitigate the thrombotic risk,” said Prof Kenet, who is also Director of the Israeli National Hemophilia Center at Sheba Medical Center.

Another key serious adverse event was an increase in ALT and AST markers above the upper normal limit, which occurred in 3% of the patients treated by replacement or bypassing agents, but 25% of those in the fitusiran arm.

However, “overall none of these elevations were sustained and they were all resolved in the median time of 2 to 3 months, and none of these patients left the study because of hepatotoxicity,” Prof. Kenet confirmed.

Also of note, five patients in the fitusiran study were diagnosed with cholecystitis and five with choleostatis, but the mechanism for that “is still being evaluated”.

The study was funded by Sanofi and Alnylam Pharmaceuticals.