ASH Clinical News February 2017 New | Page 42

Affordable Care Act
• ensuring that expensive hematologic treatments are not placed in higher tiers where they require coinsurance rather than a copayment
• allowing Medicare to negotiate drug prices with industry
These issues will all be on the agenda for the ASH ’ s Committee on Government Affairs and Committee on Practice ’ s annual “ Hill
INDICATIONS AND USAGE
ADYNOVATE , Antihemophilic Factor ( Recombinant ), PEGylated , is a human antihemophilic factor indicated in children and adults with hemophilia A ( congenital factor VIII deficiency ) for :
• On-demand treatment and control of bleeding episodes
• Perioperative management
• Routine prophylaxis to reduce the frequency of bleeding episodes
Limitation of Use ADYNOVATE is not indicated for the treatment of von Willebrand disease . CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE , to the parent molecule ADVATE ® ( Antihemophilic Factor [ Recombinant ]), mouse or hamster protein , or excipients of ADYNOVATE ( e . g . Tris , mannitol , trehalose , glutathione , and / or polysorbate 80 ).
WARNINGS AND PRECAUTIONS Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE . Allergic-type hypersensitivity reactions , including anaphylaxis , have been reported with other recombinant antihemophilic factor VIII products , including the parent molecule , ADVATE . Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema , chest tightness , dyspnea , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur .
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 .
Monitoring Laboratory Tests
• Monitor plasma factor VIII activity by performing a validated one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained .
• Monitor for the development of factor VIII inhibitors . Perform the Bethesda inhibitor assay to determine if factor VIII inhibitor is present . If expected factor VIII activity plasma levels are not attained , or if bleeding is not controlled with the expected dose of ADYNOVATE , use Bethesda Units ( BU ) to determine inhibitor levels .
ADVERSE REACTIONS The most common adverse reactions ( ≥1 % of subjects ) reported in the clinical studies were headache and nausea .
Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice .
The safety of ADYNOVATE was evaluated in 237 previously treated patients ( PTPs ) and 6 previously untreated patients ( PUPs ) with severe hemophilia A ( factor VIII less than 1 % of normal ), who received at least one dose of ADYNOVATE in 3 completed multicenter , prospective , open label clinical studies and 4 ongoing clinical studies . The median duration of participation per subject was 401 ( min-max : 3-1034 ) days and the median number of exposure days to ADYNOVATE per subject was 111 ( min-max : 1-322 ). Table 1 lists the adverse reactions reported during clinical studies .
Days ,” when committee members visit congressional offices to advocate for legislation supporting these initiatives . For more on ASH ’ s advocacy efforts , and how to get involved , see the SIDEBAR ( page 41 ).
“ At this point , all of us just want to make sure that there is affordable , highquality health care available for all Americans – many of whom are afflicted with cancer and other hematology disorders ,” said Ms . Leous .
ADYNOVATE ® [ Antihemophilic Factor ( Recombinant ), PEGylated ] Lyophilized Powder for Solution For Intravenous Injection Brief Summary of Prescribing Information : Please see package insert for full Prescribing Information .
What to Expect When You ’ re Expecting an ACA Repeal
Despite the apparently widespread acrimony about the ACA , there are parts of the legislation that are universally popular – even among those who consider the overall plan a disappointment . A recent Kaiser Health Tracking Poll found that many Trump supporters agreed with the provisions outlined in the ACA .
Here ’ s a rundown of what replacement
Table 1 : Adverse Reactions Reported for ADYNOVATE
MedDRA System Organ Class
Gastrointestinal Disorders Immune System Disorder Nervous System Disorders Skin and Subcutaneous Tissue Disorders Vascular Disorders
MedDRA Preferred Term
Number of Subjects n (%) ( N = 234 )
Rate of AEs per 100 Infusions ( N = 30865 )
Diarrhea
1 ( 0.4 %)
0.003
Nausea
2 ( 0.8 %)
0.006
Hypersensitivity a 1 ( 0.4 %) 0.003
Headache 5 ( 2.1 %) 0.026 Rash 1 ( 0.4 %) 0.003 Flushing 1 ( 0.4 %) 0.003 a
The event of hypersensitivity was a mild transient non-serious rash , occurring in one 2-year old patient who had developed a previous rash while on ADYNOVATE .
Two cases of acute pancreatitis , with no precipitating cause identified in one case , were reported in adults during an extension study of the clinical trial which evaluated 137 subjects . Administration of ADYNOVATE continued and both cases resolved .
Immunogenicity
The risk of the development of factor VIII inhibitors with the use of ADYNOVATE was evaluated in 3 completed and 4 ongoing clinical trials . Subjects consisted of adolescent and adult ( n = 148 with ≥150 prior EDs ) and pediatric PTPs [(< 6 years of age with ≥50 prior EDs ( n = 32 ), ≥6 years of age with ≥150 prior EDs ( n = 57 )], and pediatric PUPs ( n = 6 ). In 191 adult and pediatric PTPs who were treated for at least 50 exposure days with ADYNOVATE , the factor VIII inhibitor frequency was 0 ( 95 % CI of 0 to 0.019 ). One PUP subject from an ongoing study , who received at least one infusion of ADYNOVATE , developed neutralizing antibodies to factor VIII .
Immunogenicity also was evaluated by measuring the development of binding IgG and IgM antibodies against factor VIII , PEGylated ( PEG ) -factor VIII , PEG and Chinese hamster ovary ( CHO ) protein using validated ELISA assays . The majority of subjects ( 238 / 243 ) with at least one infusion of ADYNOVATE did not develop a persistent binding antibody response to any of these antigens . Twenty-eight subjects in total showed pre-existing antibodies to factor VIII ( n = 3 ), PEG-factor VIII ( n = 25 ) and / or PEG ( n = 3 ) prior to the first exposure to ADYNOVATE . Thirteen subjects who tested negative at screening developed transient antibodies against factor VIII ( n = 6 ), or PEG-FVIII ( n = 8 ) at one or two consecutive study visits . Antibodies were transient and not detectable at subsequent visits . Five subjects showed positive results for binding antibodies at study completion or at the time of data cutoff . Binding antibodies that were detected prior to exposure to ADYNOVATE , that transiently developed during the trial or were still detectable at study completion or data cutoff could not be correlated to any impaired treatment efficacy or altered PK parameters . There was no causal relationship between observed adverse events and binding antibodies except in one subject where a causal relationship cannot be ruled out based on available data . No subject had pre-existing or treatment-emergent antibodies to CHO protein .
The detection of antibodies that are reactive to factor VIII is highly dependent on many factors , including : the sensitivity and specificity of the assay , sample handling , timing of sample collection , concomitant medications and underlying disease . For these reasons , comparison of the incidence of antibodies to ADYNOVATE with the incidence of antibodies to other products may be misleading .
Baxalta , Advate , Adynovate , and Baxject are trademarks of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc .
Baxalta US Inc . Westlake Village , CA 91362 USA U . S . License No . 2020 Issued 12 / 2016 16I045-ADY-US S24588 01 / 17 legislation is likely to keep , what it is likely to toss , and what is still up for debate .
On the Way Out Falling along party lines , Republicans are opposed to the increased regulations imposed by the ACA , both on insurers and on consumers . Conservatives would like to structure a plan in which people pay for only the coverage they want . Insurance companies in this situation would function more like a free market ; ideally , competition would increase and costs would decline for both insurers and the government .
The ACA ’ s individual mandate and the Essential Health Benefits program have always been unpopular among Republicans , who argue that these provisions limit personal liberties and cost the government billions in subsidies . Proposed Republican plans require patients to maintain continuous coverage to avoid being dropped or charged for a pre-existing condition ( based on the assumption that people could be charged more if they try to obtain insurance only when they are sick ). They also allow insurers to charge consumers based on their risk / cost status , which the ACA did not allow , except according to age and tobacco use . This provision could inflate insurance costs for hematology patients who frequently require expensive care .
Here to Stay Most Republicans are in clear agreement about certain provisions of the ACA they ’ d like to keep , such as prohibiting insurers from denying coverage due to pre-existing conditions . This is an issue of particular importance to the hematology community , as many of these disorders are considered preexisting . “ Before , people with hemophilia or a prior history of leukemia had a snowball ’ s chance in hell of getting health insurance . If they did get it , the cost would be exorbitant or the coverage inadequate ,” Dr . Alvarnas recounted .
The ACA addressed this coverage gap and , as far as can be discerned at the time of this publication , the dismantlers of the ACA intend to maintain the provision .
According to GOP legislators ’ remarks , they also plan to keep the provision that allows adult children to stay on their parents ’ insurance plans until age 26 .
Moving away from fee-for-service systems and toward value-based care that emphasizes care coordination and penalizes providers for preventable hospitalizations has also garnered bipartisan support .
Up for Debate Since the ACA ’ s implementation , millions of people who would have been uninsured have gained coverage , largely due to Medicaid expansion , which has
February 2017