Roche has confirmed the death of a patient in a late-stage trial of possible haemophilia blockbuster emicizumab (ACE910).
The HAVEN 1 trial is testing emicizumab in people 12 years of age or older with haemophilia A and factor VIII inhibitors - an immune reaction that can limit the effectiveness of conventional drugs for the disease.
The drug targets clotting factors IXa and X and mimics the function of factor VIII, so if it reaches the market it would provide a new treatment for haemophilia A patients who develop inhibitors to factor VIII drugs, reducing their ability to stop blood clots.
The Swiss drugmaker told the European Haemophilia Consortium (EHC) in a letter that another patient had experienced two separate serious adverse events, and in this case the reactions resulted in his death.
The patient developed a serious rectal haemorrhage but declined blood infusions, and then went on to develop blood clots in small blood vessels (thrombotic microangiopathy), a complication that in some cases is known to progress to organ injury.
While the clinical investigator in the study has indicated that the drug was not likely to have played a factor in the death, the new serious adverse events follow four others reported last November, and elevate concerns about the safety profile of emicizumab, which is scheduled for filing later this year if HAVEN-1 hits its objectives.
The earlier adverse reactions were seen when emicizumab was given alongside "multiple doses of a bypassing agent" (activated prothrombin complex concentrates or aPCCs), a drug class used as a rescue therapy for breakthrough bleeds which includes Shire's Feiba and Novo Nordisk's NovoSeven.
An aPCC was also used in the patient who died in HAVEN 1, according to Roche.
Bernstein analyst Ronny Gal said the latest development "is not a death sentence for [Roche's drug] in any way, shape or form, but it does increase requirement for them to come up with a good answer for how a patient can be rescued."
Roche is not planning to suspend the trial, and said the current guidance to avoid aPCCs unless essential and then use the lowest dose possible "remains appropriate".
The company reported positive efficacy data with emicizumab last December that prompted some analysts to predict potential blockbuster sales for the drug thanks to a better route of administration, less frequent dosing, and improved efficacy compared to current drugs.
Analysts have previously suggested that emicizumab could attack around half the revenues of NovoSeven, which made sales of almost $1.4bn in 2016, and eat into the $900m posted by Shire for its Feiba drug.
That competitive edge is mainly because it is given as a weekly dose to prevent bleeds while its rivals are used as on-demand treatment. If TMA emerges as an issue for the monotherapy it could limit its use in non-inhibitor patients, a much larger market.