Errata – FDA Briefing Document

Cinryze^TM (C1-esterase Inhibitor (Human) Nanofiltered (C1INH-nf)

Lev Pharmaceuticals, Inc.

 

Blood Products Advisory Committee Meeting

May 2, 2008

 

 

 

Editorial and formatting changes were made to the briefing document.  The substantive revisions to the document are listed below.

 

1. Page 6, 4^th paragraph: added sentence, “FDA proposes the performance of postmarketing studies to evaluate dosing regimens.”
2. Page 6, 5^th paragraph:  revised last sentence to read “FDA proposes postmarketing studies to evaluate this issue further.”
3. Page 6, 6^th paragraph:  added sentence, “FDA proposes postmarketing safety monitoring to evaluate the effects of repeated and long-term treatment.”
4. Page 9, 5^th line, added phrase, “of affected individuals.”
5. Page 10, 5^th paragraph:  changed “90 d” to “12 wks” in two instances  
6. Page 10, 5^th paragraph, 6^th line:  added phrase, “if treated”
7. Page 11, section h:  changed “90 d” to “12 wks”
8. Page 15, Table 3:  added title, “Completed Safety and Efficacy Studies with Cinryze^TM (C1INH) Conducted by Lev Pharmaceutical, Inc (Part B).
9. Page 17, 1^st paragraph, last sentence:  revised to read, “Subjects who reported a history of a high frequency of HAE attacks (2-3 per month) were enrolled into Part B.  
10. Page 17, 2^nd and 3^rd paragraph:  changed “90 d” to “12 weeks”  in four instances
11. Page 17, 2^nd paragraph, 6^th line: added phrase, “if treated”
12. Page 19, Table 6:  rounded data to 2 decimal points
13. Page 20, 1^st paragraph, 3^rd line:  revised sentence to read, “Sequence or period effects did not confound the results.”
14. Page 23, 2^nd paragraph, 2^nd sentence:  revised to read, “In Part A the C1INH arm had 36 subjects (27 female, 9 male), the placebo arm had 35 subjects (28 female, 7 male).
15. Page 24, 3^rd paragraph:  revised to read, “However, repeat testing of samples at the same laboratory produced inconsistent results prompting analysis at alternate laboratories.  Of these 329 subjects, 119 were tested at a second laboratory.  Among these 119 subjects, 2 (0.8%) tested positive at the second laboratory...”
16. Page 24, 4^th paragraph:  revised to read “…antibody results were obtained for 19 subjects at the end of Part B and/or at the 3 month follow up.  Of these 19 subjects, 10 exhibited a positive result for C1INH antibodies as reported by the first laboratory.  Of these 10 subjects, 2 reported a positive result (bound and/or free Ab) at screening.”
17. Page 24, 5^th paragraph, 1^st and 2^nd sentences:  revised to read, “Of the remaining 8 subjects, 6 had modest elevations in antibody levels.  However, 2 subjects (Patients 59-001 and 16-005) appeared to have notable antibody response.”
18. Page 24, 6^th paragraph, last sentence:  revised to read, “Resolution of this issue may require postmarketing studies.”
19. Page 25, Table 10:  subject 06-001: revised to “Y”; added subjects “51-001, Y, 60%” and “17-002, Y, -85%”
20. Page 26, 3^rd paragraph: changed “90 days” to “12 weeks”
21. Page 27, 1^st paragraph: added sentence, “When expressed as adverse events per infusion, the rates for Cinryze^TM and placebo are the same (0.068).”
22. Page 27, 3^rd paragraph: added sentence, “However, since prophylaxis involves repeated and long-term treatment, post marketing safety monitoring may be required.”
23. Page 28, 2^nd paragraph: changed “90 days” to “12 weeks” in 6 instances
24. Page 31, question 2:  revised to read, “If the answer to Question #1 is yes, should post marketing studies be performed to further evaluate the following:  a) --- b)---c) long-term safety.”
25. Page 39, Appendix 4:  amended the table based on FDA’s analysis of the data in Table named “Log10 Reduction Factor for Selected Viruses.”  Deleted the name of the table and added footnote, “FDA analysis of sponsor’s data.”