- Swiss pharma giant Roche reported this week the death of a patient enrolled in a Phase 3 trial testing its experimental treatment for hemophilia A, raising further concerns about the safety profile of the potential blockbuster drug, known as emicizumab or ACE910.
- The patient was treated with bypassing agents after experiencing a serious rectal hemorrhage while on emicizumab, but developed signs of thrombotic microangiopathy and later died, the pharma company said in a statement to the European Haemophilia Consortium.
- The Phase 3 study in question, HAVEN 1, is testing emicizumab in hemophilia A patients with inhibitors to the clotting Factor VIII. Top-line results released in December last year showed the antibody drug reduced the number of bleeds over time, bolstering its potential to steal market share away from market leaders Novo Nordisk and Shire.
The patient death, while judged not related to emicizumab by the trial investigator, adds to the safety questions surrounding the drug. Four serious adverse events, including two cases of thrombotic microangiopathy, were reported last November in patients being treated for breakthrough bleeds while enrolled in Roche's trial.
At the time, analysts saw the safety signals as suggesting emicizumab might not completely control bleeding in hemophilia A patients, leading to the need for bypassing agents which carry the risk of thrombosis. All four adverse events were resolved, however, and two patients restarted emicizumab with no further problems.
A clean sweep of all primary and secondary endpoints in the high level results reported in December helped to bolster the drug's prospects, though, and Roche plans to file for approval in the U.S. and E.U. this year for patients with inhibitors.
Despite the new safety signal, Roche believes its current trial protocol remains appropriate and will continue to investigate the details of the death.
But the news helped lift shares of Novo Nordisk and Shire, two leaders in the hemophilia space which would be threatened by emicizumab. Novo stock rose by about 1% in early Thursday trading, while Shire was up nearly 2%.
Novo's hemophilia treatment NovoSeven may face the greatest risk of competition from emicizumab as it is one of the only other treatments for patients who have developed inhibitors to factor replacement therapies.
NovoSeven pulled in 9,492 million Danish kroner (roughly $1.4 billion using average 2016 exchange rates), but has already felt an impact from hemophilia patients discontinuing treatment to take part in clinical trials for emicizumab.
Emicizumab is seen as such a competitive threat due to how it is designed to work. NovoSeven, and other traditional hemophilia drugs, treat bleeds as they happen. Emicizumab, on the other hand, is a preventative treatment, taken weekly, that could dramatically change how these patients are treated. Furthermore, the pool of patients with inhibitors is relatively small, meaning a highly effective preventative treatment could significantly dent Novo's revenues.
But other game-changing treatments are also on the horizon. Alnylam is currently in early- to mid-stage testing of an RNA interference drug known as fitusiran for patients with either hemophilia A or B, and with or without inhibitors. Company CEO John Maraganore has said emicizumab will likely be the main competition for fitusiran.