Letters to the Editor
Not-So-NICE One
In December 2016 , we published an Online Exclusive item on ashclinicalnews . org reporting on the United Kingdom ’ s National Institute for Health and Care Excellence ’ s ( NICE ) review of two multiple myeloma drugs (“ NICE Rejects Two Multiple Myeloma
IDELVION ® [ Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ] Lyophilized Powder for Solution for Intravenous Injection Initial U . S . Approval : 2016
BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use IDELVION safely and effectively . See full prescribing information for IDELVION .
----------------------------INDICATIONS AND USAGE--------------------------- IDELVION , Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ( rIX- FP ), a recombinant human blood coagulation factor , is indicated in children and adults with hemophilia B ( congenital Factor IX deficiency ) for :
• On-demand control and prevention of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes Limitations of Use : IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B .
------------------------DOSAGE AND ADMINISTRATION------------------------ For intravenous use after reconstitution only . Each vial of IDELVION is labeled with the actual Factor IX potency in international units ( IU ).
• One IU of IDELVION per kg body weight is expected to increase the circulating activity of Factor IX as follows :
° Adolescents and adults : 1 . 3 IU / dL per IU / kg ° Pediatrics (< 12 years ): 1 IU / dL per IU / kg
• Administer intravenously . Do not exceed infusion rate of 10 mL per minute . Control and prevention of bleeding episodes and perioperative management :
• Dosage and duration of treatment with IDELVION depends on the severity of the Factor IX deficiency , the location and extent of bleeding , and the patient ’ s clinical condition , age and recovery of Factor IX .
• Determine the initial dose using the following formula :
• Required Dose ( IU ) = Body Weight ( kg ) x Desired Factor IX rise (% of normal or IU / dL ) x ( reciprocal of recovery ( IU / kg per IU / dL ))
• Adjust dose based on the patient ’ s clinical condition and response .
Routine prophylaxis :
• Patients ≥12 years of age : 25-40 IU / kg body weight every 7 days . ( 2.1 ) Patients who are well-controlled on this regimen may be switched to a 14-day interval at 50-75 IU / kg body weight .
• Patients < 12 years of age : 40-55 IU / kg body weight every 7 days .
Drugs , Citing Lack of Cost-Effectiveness Data ”), based partly on source material that contained inaccurate information . We apologize for the errors and would like to thank David Bowen , MD , a NICE Appraisal Committee ( AC ) member , for providing an
-------------------------DOSAGE FORMS AND STRENGTHS---------------------- IDELVION is available as a lyophilized powder in single-use vials containing nominally 250 , 500 , 1000 or 2000 IU .
-----------------------------CONTRAINDICATIONS ------------------------------- Do not use in patients who have had life-threatening hypersensitivity reactions to IDELVION or its components , including hamster proteins .
--------------------------WARNINGS AND PRECAUTIONS-----------------------
• Hypersensitivity reactions , including anaphylaxis , are possible . Should symptoms occur , discontinue IDELVION and administer appropriate treatment .
• Development of neutralizing antibodies ( inhibitors ) to IDELVION may occur . If expected Factor IX plasma recovery in patient plasma is not attained , or if bleeding is not controlled with an appropriate dose , perform an assay that measures Factor IX inhibitor concentration .
• Thromboembolism ( e . g ., pulmonary embolism , venous thrombosis , and arterial thrombosis ) may occur when using Factor IX-containing products .
• Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX .
• Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used .
----------------------------ADVERSE REACTIONS--------------------------------- The most common adverse reaction ( incidence ≥1 %) reported in clinical trials was headache .
To report SUSPECTED ADVERSE REACTIONS , contact CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800- FDA-1088 or www . fda . gov / medwatch .
----------------------USE IN SPECIFIC POPULATIONS---------------------------
• Pediatric : Higher dose per kilogram body weight or more frequent dosing may be needed .
Based on March 2016 version .
informed look at the NICE review process in the following commentary .
To the ASH Clinical News Editorial Staff :
The recent news item published on ASH Clinical News ’ website contains factual inaccuracies .
First , NICE has not rejected either of these agents . Both of the agents mentioned in the article ( lenalidomide and carfilzomib ) are only at the Appraisal Consultation Document ( ACD ) stage of review ; this is a major omission of fact .
The ACD is produced following a first committee meeting of the NICE AC , in which the committee assesses the clinical and cost-effectiveness evidence presented by the pharmaceutical company , and also assesses the critique from the academic Evidence Review Group . The ACD sets out the preliminary conclusions based on the evidence presented and a critique of this evidence . All stakeholders then digest the ACD and return to a second committee meeting to respond to the issues raised and to re-evaluate the evidence in a second round .
After the second committee meeting , when all stakeholders ( principally the pharmaceutical company ) have made their case , NICE usually issues the Final Appraisal Determination ( FAD ) – though sometimes more than two committee meetings are required before releasing the FAD . This is ostensibly NICE ’ s “ final say ,” but it often is appealed formally and sometimes goes on to judicial review . The UK ’ s National Health Service then implements the guidance in the FAD .
Second , the carfilzomib ACD judgement was not reached because “ committee members also could not agree on a cost-effectiveness estimate ,” as the article stated . The AC did not consider that the evidence presented by the company could be used to create a cost-effectiveness output because of disagreement with the company ’ s modelling and statistical methods . The AC themselves all agreed ; the company model was inadequate .
– David Bowen , MD Honorary Professor of Myeloid
Leukemia Studies and Consultant Hematologist
St James ’ s Institute of Oncology Leeds , United Kingdom
Have a comment about an article ? Let us know what you think ; we welcome your feedback . Email the editor at ACNEditor @ hematology . org .
March 2017