Once weekly prophylaxis with emicizumab leads to a significantly lower bleeding rate in people with severe haemophilia A without factor VIII inhibitors compared to no prophylaxis or previous treatment with factor VIII prophylaxis, a phase 3 trial has shown.

A study of 152 patients from age 12 years extends an earlier efficacy and safety study in people with haemophilia who had developed anti-factor VIII alloantibodies.

The novel bispecific monoclonal antibody, which bridges activated factor IX and factor X to replace the function of activated factor VIII, offers the advantage of weekly or fortnightly subcutaneous injections compared to IV administration of factor VIII concentrate three times per week.

The study found patients receiving either 1.5mg/kg weekly or 30mg/kg fortnightly emicizumab had annualised bleeding rates of 1.5 or 1.3 events respectively compared to 38.2 events with no prophylaxis.

No treated bleeding events were reported in 56% of people receiving weekly emicizumab and 60% of people receiving the fortnightly doses while all people without prophylaxis had bleeding events.

An annualised bleeding rate of 1.5 events demonstrated in a fourth group of patients who received the weekly emicizumab regimen compared favourably to a rate of 4.8 events in the same individuals when they were previously given factor VIII prophylaxis.

The study found emicizumab had a favourable safety profile with mostly injection-site reactions and few serious adverse events. It also reduced the injection burden for patients who currently need twice-weekly injections with factor VIII, the study authors added.

Associate Professor Huyen Tran, director of the Ronald Sawers Haemophilia Centre at the Alfred Hospital, Melbourne, told the limbic he has patients whose lives have been turned around by emicizumab in the context of a clinical trial.

“The efficacy comparison with placebo is not so relevant in Australia because virtually all of our severe haemophiliacs are on prophylaxis. What is relevant to our standard of care is the comparison to the patients who had been receiving factor VIII concentrate prophylaxis.”

“The only unknown, and we just need to be cautious, is the potential synergistic effects or interactions if we had to give Factor VIII concentrate for breakthrough bleeds.”

He said emicizumab would be restricted to patients with severe haemophilia A only and will eventually apply to both patients with and without factor VIII inhibitors.

“And despite this drug, if they get involved in a car accident or are playing sport and get a knock, they can still have a bleed. In that instance, they would still need factor VIII concentrate in a short period of time until we control that bleed.”

He said oversight of the use of emicizumab through haemophilia centres would be important.

“This is a rare disease with significant complications and when it comes to rare disease, you need collective knowledge. We don’t want this drug to be placed on the PBS [so that] any doctors can prescribe it.”

“In terms of funding, there is a bit of work to be done because historically, haemophilia care has fallen under the National Blood Authority (NBA),” he said.

“Wearing my other hat as chair of the Australian Haemophilia Centre Directors’ Organisation (AHCDO) we interact with the NBA at least four times per year and are working through this process in terms of funding and its management.”

He added there were other novel agents on the horizon including gene therapy.

“So the whole treatment domain in haemophilia at the moment is really dynamic.”