Roche Reports Death in Phase III Hemophilia Study
February 23, 2017
By Mark Terry, BioSpace.com Breaking News Staff
Swiss-based Roche reported a death in its ACE910 study of emicizumab in patients with hemophilia A and factor VIII inhibitors.
The information was released by the European Hemophilia Consortium. The patient was in the HAVEN 1 Phase III trial to study the safety and efficacy of emicizumab in patients 12 years or older with hemophilia A and factor VIII inhibitors. They had two reports of Serious Adverse Events (SAE) in one patient, who died.
The statement indicates the patient experienced a serious rectal hemorrhage, which was the first SAE. The patient was treated with bypassing agents, including multiple doses of activated prothrombin complex (aPCC). The patient then developed Thrombotic Microangiopathy (TMA), which was the second SAE.
Roche said in a statement, “The preliminary assessment is that the clinical and laboratory characteristics of this case of TMA are consistent with what was observed in the two previously reported cases; however, our evaluation of the available information is ongoing.”
Although still investigating, Roche and the Consortium indicate that treatment of the hemorrhage was complicated due to the patient declining blood transfusions. The cause of death has been determined to be the rectal hemorrhage, but that it is not related to emicizumab.
Roche stated, “We have developed our guidance in consultation with our independent data monitoring committee (IDMC), which includes highly respected scientific and clinical hemophilia experts. We will be evaluating the information from this particular case in the context of the other information from our on-going clinical trials. We look forward to presenting data from the HAVEN 1 study of emicizumab in people with hemophilia A and inhibitors to factor VIII, which will provide better context for the overall benefit/risk profile of emicizumab in this patient population, at an upcoming medical conference.”
In late December 2016, Roche announced that in the HAVEN 1 Phase III trial the primary endpoint had been met. The study showed a statistically significant decrease in the number of bleeds over time in individuals receiving emicizumab prophylaxis compared to those receiving no prophylactic treatment. In addition, it had its secondary endpoints, including a statistically significant reduction in the number of bleeds over time with the drug in an intra-patient comparison in individuals who had received prior bypassing agent prophylaxis treatments.
“The development of inhibitors that render factor VIII replacement less effective, or ineffective, is one of the greatest challenges in the treatment of hemophilia A today, putting patients at high risk of life-threatening bleeds and repeated bleeds that may cause long-term joint damage,” Sandra Horning, Roche’s chief medical officer and Head of Global Product Development, said in a statement at the time. “We are pleased to see that, in our first pivotal trial, emicizumab prophylaxis significantly reduced the number of bleeds over time in people in this difficult-to-treat setting. We look forward to working with health authorities to bring this treatment to the hemophilia community as soon as possible.”
In that announcement, the company also reported two patients had thromboembolic events and two patients developed thrombotic microangiopathy (TMA). The commonality in all the cases was that they were patients on emicizumab prophylaxis that were receiving activated prothrombin complex concentrate to treat breakthrough bleeds. But in those cases, neither thromboembolic event required anti-coagulation therapy. One patient restarted emicizumab. Both TMA cases were resolved and one of the patients restarted with the drug.
Emicizumab is a bispecific monoclonal antibody that brings together factors IXa and X. These proteins are required to activate the natural coagulation cascade and restore normal blood clotting.