More on HemLibra

More on HemLibra
Oct 15, 2018 12:35pm

I follow-up to our October 6, 2018 post describing emicizumab (HemLibra), I have correspondence dated 9/10/18 from Paul Riley, PhD, MBA, Stago Scientific Business Development Manager for North America.

Paul writes, "I was wondering if you should put something on FF about emicizumab, like a survey to find out how people are deiling with it and if they have patients transitioning to that therapy. Here is some information I put together recenly on it in order to give good guidance to our customers when the have questions. There is another approval expected shortly for non-inhibitor patients transitioned over despite there having been several deaths reported recently in patients taking emicizumab." [Added by George, this approval is now in place. also, while it addressed the limitations of the one-stage clotting assay relative to extended half-life factor VIII, the results of our June, 2018 Quick Question, "How do you measure factor VIII?" have a direct bearing on the emicizumab issue]  Paul provides this table for hemophilia A monitoring.

Hemophilia A1 Therapy Classes and Monitoring

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.

 

 

 

1 Comment

I follow-up to our October 6, 2018 post describing emicizumab (HemLibra), I have correspondence dated 9/10/18 from Paul Riley, PhD, MBA, Stago Scientific Business Development Manager for North America.

Paul writes, "I was wondering if you should put something on FF about emicizumab, like a survey to find out how people are deiling with it and if they have patients transitioning to that therapy. Here is some information I put together recenly on it in order to give good guidance to our customers when the have questions. There is another approval expected shortly for non-inhibitor patients transitioned over despite there having been several deaths reported recently in patients taking emicizumab." [Added by George, this approval is now in place. also, while it addressed the limitations of the one-stage clotting assay relative to extended half-life factor VIII, the results of our June, 2018 Quick Question, "How do you measure factor VIII?" have a direct bearing on the emicizumab issue]  Paul provides this table for hemophilia A monitoring.

Hemophilia A1 Therapy Classes and Monitoring

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.

 

 

 

By Dean
Oct 16, 2018 1:46pm
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

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