| FVIII Inhibitor? | Y/N | Y/N | Y/N |
| Prophylaxis | Conventional half-life recombinant or plasma-derived FVIII concentrate |
Extended half-life recombinant FVIII concentrate | Emicizumab |
| Assay for measuring activity | OSA or CSA2 | OSA3 or CSA using human or bovine materials | CSA with human materials or OSA using emicizumab calbrators and controls.4 |
1. Discrepancies between one-stage clot-based assays (OSA) and chromogenic substrate assays (CSA) have been reported for certain FVIII mutations associated with non-severe hemophilia A and may hinder identification of patients for therapy.
2. CSA may overestimate the level in case of FVIII missense mutations located in FVIII thrombin cleavage and FIXa binding sites.
3. Use of OSA depends on therapy and the OSA activator.
4. Can perform the Nijmegen Bethesda assay by CSA using bovine materials if assaying inhibitor titer or attempting to monitor FVIII concentrate for breakthrough bleeding in presence of emicizumab. Click here for Precision BioLogic’s July 20 news release and poster describing our newly developed Nijmegen Bethesda Assay.
George checked on Thursday, October 11, 2018 to learn that our facility in Birmingham has converted three hemophilia A patients with inhibitors to emicizumab at an annual cost of $430,000 to the payer. This is less than the average annual costs for current hemophilia A with inhibitor management, including cost of monitoring, therapeutics, and bleeds.
References for emicizumab effects of FVIII and inhibitor measurement:
1. Adamkewicz J, Kim B, Steinbuesch D, Calatzis A. Measurement of FVIII inhibitor titer using a chromogenic Nijmegen Bethesda assay in the presence of emicizumab (ACE910), a humanized bispecific antibody mimicking FVIIIa cofactor function. HTRS 2017 (Abstract)
2. Adamkewicz J, Soeda T, Kotani N, Calatzis A, Levy G. Effect of emicizumab (ACE910)–a humanized bispecific antibody mimicing FVIIIa cofactor function–on coagulation assays commonly in use for monitoring of hemophilia A patients. HTRS 2017 (Abstract)
3. Tiefenbacher S, Shrotriya S, Robinson MR, Adamkewicz J, Steinbuesch D. Validation of a FVIII chromogenic Bethesda assay for the detection of inhibitors in the presence of emicizumab (ACE910). THSNA 2018 (Abstract)
4. Calhoon W, McInerney M, Calatzis A, Chen DC, Adamkewicz J, Morris M. Evaluation of a dedicated calibrator and controls for emicizumab quantification. THSNA 2018 (Abstract)
5. Al-Samkari H, Croteau SE. Shifting landscape of hemophilia therapy: implications for durrent clinical laboratory coagulation assays. Am J Hematol. 2018 Jun 8.
Thanks Geo (and Paul). I was
Thanks Geo (and Paul). I was interested to see your comment regarding the cost of Hemlibra treatment. I’ve heard some skepticism regarding how well this revolutionary therapy would be adopted because of a perception that the cost would be prohibitive. I’m happy to hear that wasn’t the experience in Birmingham and hopeful that it will be replicated elsewhere.
Here’s a link to a story that brings the impact of Hemlibra into focus. We’ve heard a number of other patient stories that echo this family’s experience. Really powerful stuff. I had to use Google Chrome to get the video to play.
https://www.ihtc.org/news/?newsname=fox59-fda-approves-new-bleeding-disorder-drug