FEATURE dysplasia . 6 In the study , though , we did not include the third category of MRC , multilineage dysplasia ; however , some research has suggested that their prognosis does not differ from other subsets of patients with AML-MRC . Furthermore , to make the diagnosis of MRC based on multilineage dysplasia per the WHO criteria , we would need to exclude the presence of NPM1 and biallelic CEBPA mutations . This molecular information often is not available when making the initial treatment choice .
However , I would argue that you should strongly consider using CPX-351 in a patient who has one of these high-risk features , because our goal with younger patients is to get them into a complete remission and then perform alloHCT , with the least toxicity possible . As was shown in the pivotal trial , more people went on to transplant ( even in older participants who are more susceptible to toxicity ) and experienced better outcomes post-transplant when receiving CPX-351 induction .
The reason for the pivotal study being done in the selected population was because this was the subset where we believed CPX-351 was going to perform better than 7 + 3 , but in the broader randomized , phase II study , there wasn ’ t a subset where CPX-351 did worse .
Dr . Stone : I do think CPX-351 needs to be tested against 7 + 3 in a broader population because , as you pointed out , it wasn ’ t that it was bad in the nonsecondary AML patients , but it just wasn ’ t better . Yet , if we performed a large trial of CPX-351 versus 7 + 3 , CPX-351 might perform better , depending on the selected endpoint .
Clinical study results in children and adults receiving prophylactic treatment over a 6-month period 1 , 2
The efficacy , safety and PK of ADYNOVATE were evaluated in 2 multicenter , open-label clinical studies . The pediatric study of children < 12 years of age ( N = 66 ) evaluated the immunogenicity , efficacy , PK ( as compared to ADVATE ® [ Antihemophilic Factor ( Recombinant )]), and safety of ADYNOVATE twice-weekly prophylaxis ( 40-60 IU / kg ) and determined hemostatic efficacy in the treatment of bleeding episodes for 6 months . The pivotal trial of children and adults ≥12 years ( N = 137 ) evaluated ADYNOVATE twice-weekly prophylaxis ( 40-50 IU / kg ) vs on-demand ( 10-60 IU / kg ) treatment , and determined hemostatic efficacy in the treatment of bleeding episodes for 6 months . 1-3
Proven prophylaxis with ADYNOVATE
ZERO
MEDIAN ABR FOR JOINT & SPONTANEOUS 1
In pediatric patients < 12 years : Joint : 0.0 ( IQR : 1.9 ) median ABR 3 ; Spontaneous : 0.0 ( IQR : 1.9 ) median ABR . 3
In adults and children ≥12 years : Joint : Prophylaxis 0.0 ( IQR : 2.0 ) median ABR vs on-demand 38.1 ( IQR : 20.1 ) median ABR . 1 , 3 Spontaneous : Prophylaxis 0.0 ( IQR : 2.2 ) median ABR vs on-demand 21.6 ( IQR : 22.0 ) median ABR . 1 , 3
Consistent dosing1
+ In the clinical studies , the majority of children and adults did not have a dose adjustment 1 , 2
+ 98 % of adults and children ( 12 years and older ) did not have a dose adjustment ( 118 of 120 ) 1 — Two subjects increased their dose to 60 IU / kg due to bleeding in target joints
+ 91 % of children ( less than 12 years ) did not have a dose adjustment ( 60 of 66 ) 2 — Reported reasons for dose adjustment included FVIII trough levels < 1 %, increased risk of bleeding , and bleeding episodes
Neutralizing Antibodies
Formation of neutralizing antibodies ( inhibitors ) to factor VIII can occur following administration of ADYNOVATE . Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests . Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected , or if bleeding is not controlled with expected dose .
ADVERSE REACTIONS
The most common adverse reactions ( ≥1 % of subjects ) reported in the clinical studies were headache and nausea .
Please see the following page for the Brief Summary of the ADYNOVATE full Prescribing Information .
For full Prescribing Information , visit www . ADYNOVATEPRO . com .
References : 1 . ADYNOVATE Prescribing Information . 2 . Mullins ES , Stasyshyn O , Alvarez-Román MT , et al . Extended half-life pegylated , full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A . Haemophilia . 2016 Nov 27 . doi : 10.1111 / hae . 13119 [ Epub ahead of print ]. 3 . Data on file .
© 2017 Shire US Inc ., Lexington , MA 02421 . All rights reserved . 1-800-828-2088 . SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates . ADVATE and ADYNOVATE are trademarks or registered trademarks of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc . S31608 05 / 17