Tokyo-based Chugai Pharmaceutical Co. Ltd., recently reported data from a Phase I, dose-escalation clinical study of Emicizumab (ACE910), the company’s investigational therapy being developed for the prophylactic treatment of people with factor VIII (FVIII) deficiency, or hemophilia A, both with and without inhibitors. Unlike existing treatments, which require intravenous injections, ACE910 is administered subcutaneously via an injection just under the skin.
Results of the study, “Factor VIII–Mimetic Function of Humanized Bispecific Antibody in Hemophilia A,” were published online, May 26, 2016, in The New England Journal of Medicine. The lead author of the article was Midori Shima, MD, PhD, Nara Medical University Department of Pediatrics in Kashihara, Japan. Emicizumab was granted breakthrough therapy status by the US Food and Drug Administration (FDA) in September 2015. Drugs designated as “breakthrough” therapies are placed by the FDA on a fast-track approval program and given intensive guidance by the agency.
ACE910, a laboratory-engineered protein, works by performing a key function in the clotting cascade that is normally carried out by the FVIII protein, which is deficient in individuals with hemophilia A. The “cascade” is an intricate series of chemical and molecular reactions between clotting factors that lead to clot formation. In this case, ACE910 binds to and bridges two other key clotting proteins, activated factor IX and factor X, important components of the cascade normally performed by FVIII. In short, ACE910 acts as a “FVIII–mimetic agent,” to ensure the creation of a viable blood clot. While ACE910 is a therapy designed specifically for prophylactic use, this does not preclude the on-demand use of additional factor therapies to treat bleeds if and when they arise.
A total of 18 subjects with hemophilia A were enrolled in Japan, with and without FVIII inhibitors, to investigate the safety and to weigh the potential benefit of emicizumab when used prophylactically to prevent bleeds. The patients were separated into three groups, with each successive group representing an increase in dosing. All patients were treated with weekly subcutaneous injections of emicizumab for 12 consecutive weeks.
Investigators compared each patient’s annualized bleeding rate (ABR), measured six months prior to study initiation and then again during the trial. The median ABR in groups 1 (lowest dose), 2 (middle dose) and 3 (highest dose) decreased significantly, from 32.5 to 4.4, 18.3 to 0.0 and 15.2 to 0.0, respectively. No bleeding events were observed in 8 of 11 patients with FVIII inhibitors (73%) and in 5 of 7 patients without FVIII inhibitors (71%). The necessity for the on-demand use of additional factor products to control bleeding was also reduced. No inhibitor antibodies were reported.
Chugai also reported that adverse effects (AEs) encountered during the study were of “mild intensity,” except for upper respiratory tract infection and headache of moderate intensity in two patients. No thromboembolic (clotting) AEs were observed, even when additional FVIII products or bypassing agents were utilized to treat bleeding events.
“A great challenge with the current treatments for hemophilia A is that these patients need frequent intravenous injections and face the possibility of developing inhibitors to FVIII,” said Chugai’s Director and Executive Vice President, Dr. Yutaka Tanaka. “The study results indicated a potential for benefit from emicizumab in treating hemophilia A patients with inhibitors with once-weekly subcutaneous injection. With these findings, we expect that emicizumab may be a new treatment option to fulfill unmet medical needs of hemophilia A patients.”
According to a Chugai news release, the company is currently conducting a Phase III global study in hemophilia A patients with FVIII inhibitors in collaboration with Roche, Chugai’s strategic alliance partner. In addition, phase III global studies in patients without FVIII inhibitors and pediatric patients are also slated to begin in 2016.
Source: Chugai news release dated May 26, 2016
