historical pml by treatment epoch october 2010

8/8/2019 Historical PML by Treatment Epoch October 2010

1/12

1

Natalizumab PML Incidence Estimates

by Treatment Epoch

Incidence

pe

r1000

patients

*Yousry TA, et al. N Engl J Med. 2006;354:924-933.Observed clinical trial rate in patients who received a mean of 17.9 monthly doses of natalizumab

Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through September 30, 2010 and 70 confirmed cases as ofOctober 1, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed to atleast 25 infusions and therefore having risk of developing PML during this time).

2.80

1.15

0.07

0.60

1.95

1.71

0.20

0.71

0.00

1.03

0.45

1.000.91

0.01

0.38

1.44

0.93

0.23

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials*

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions


2/12

2


by Treatment Epoch

2.80

1.14

0.07

0.62

1.98

1.72

0.20

0.70

0.00

1.04

0.42

1.000.90

0.01

0.39

1.46

0.91

0.23

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials*

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidenceper1000

patients


Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through August 31, 2010 and 68 confirmed cases as ofSeptember 2, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed to at

least 25 infusions but no more than 36 and therefore having risk of developing PML during this time).


3/12

3


by Treatment Epoch

2.80

1.09

0.08

0.63

1.92

1.59

0.20

0.65

0.00

0.98

0.31

1.00

0.85

0.01

0.40

1.39

0.77

0.24

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials*

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidencep

er1000

patients


Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through July 31, 2010 and 63 confirmed cases as ofAugust 4, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed toat least 25 infusions and therefore having risk of developing PML during this time).


4/12

4

NatalizumabNatalizumab PML Incidence EstimatesPML Incidence Estimates

by Treatment Epochby Treatment Epoch

*Yousry TA, et al. N Engl J Med. 2006;354:924-933.Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through June 30, 2010 and 58 confirmed cases as ofJuly 2, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed toat least 25 infusions and therefore having risk of developing PML during this time). The 95% confidence interval (CI) is an estimated range

that is 95% likely to include the true rate of PML. The width of the CI is an indication of the precision of the estimate. The wider theconfidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing the denominator of treated patients willincrease the precision of the estimates and narrow the confidence interval. There are limited data beyond three years of treatment.

2.80

1.03

0.08

0.60

1.97

1.61

0.20

0.61

0.00

0.99

0.27

1.00

0.80

0.01

0.37

1.42

0.74

0.21

0.0

0.5

1.0

1.5

2.0

2.5

3.0

ClinicalTrials*

PostMarketing

1-12Infusions

13-24Infusions

25-36Infusions

37-48Infusions

Incidence

per1000

patients


5/12

5



*Yousry TA, et al. N Engl J Med. 2006;354:924-933.Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through May 31, 2010 and 55 confirmed cases as ofJune 7, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed toat least 25 infusions and therefore having risk of developing PML during this time). The 95% confidence interval (CI) is an estimated range


2.80

1.00

0.08

0.58

2.05

1.62

0.20

0.58

0.00

1.02

0.23

1.00

0.77

0.01

0.35

1.47

0.70

0.20

0.0

0.5

1.0

1.5

2.0

2.5

3.0

ClinicalTrials*

PostMarketing

1-12Infusions

13-24Infusions

25-36Infusions

37-48Infusions

Incidence

per1000

patients


6/12

6



*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through April 30, 2010 and 49 confirmed cases as ofMay 6, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed toTYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patients ever exposed toat least 25 infusions and therefore having risk of developing PML during this time). The 95% confidence interval (CI) is an estimated range


2.80

0.92

0.08

0.54

1.971.85

0.20

0.52

0.00

0.93

0.26

1.00

0.70

0.01

0.32

1.38

0.79

0.17

0.0

0.5

1.0

1.5

2.0

2.5

3.0

ClinicalTrials PostMarketing 1-12Infusions 13-24Infusions 25-36Infusions 37-48Infusions

Incidence

per1000

Patien

ts


7/12

7

2.80

0.89

0.08

0.56

1.94

2.08

0.20

0.49

0.00

0.88

0.29

1.00

0.67

0.01

0.33

1.33

0.89

0.17

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Inciden

ce

per1000

patie

nts



*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through March 31, 2010 and 46 confirmed casesas of April 6, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patientsexposed to TYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of patientsever exposed to at least 25 infusions but fewer than 37 infusions and therefore having risk of developing PML during this time). The

95% confidence interval (CI) is an estimated range that is 95% likely to include the true rate of PML. The width of the CI is anindication of the precision of the estimate. The wider the confidence intervals in relation to the point estimate indicate a higher level ofuncertainty. Increasing the denominator of treated patients will increase the precision of the estimates and narrow the confidenceinterval.


8/12

8

2.80

0.83

0.08

0.54

2.00

1.81

0.20

0.44

0.00

0.89

0.13

1.00

0.62

0.02

0.31

1.36

0.62

0.16

0.0

0.5

1.0

1.5

2.0

2.5

3.0

ClinicalTrials

PostMarketing

1-12Infusions

13-24Infusions

25-36Infusions

37-48Infusions

Incidence

per1000

patients



*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through February 28, 2010 and 42 confirmedcases as of March 10, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number ofpatients exposed to TYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number ofpatients exposed to at least 25 infusions and therefore having risk of developing PML during this time). The 95% confidence interval

(CI) is an estimated range that is 95% likely to include the true rate of PML. The width of the CI is an indication of the precision of theestimate. The wider the confidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing thedenominator of treated patients will increase the precision of the estimates and narrow the confidence interval.


9/12

9

2.80

0.73

0.19

0.97

2.38

1.76

0.20

0.36

0.00

0.96

0.06

1.00

0.52

0.03

0.54

1.56

0.49

0.27

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidence

per

1000

patients



Incidence calculated based on natalizumab exposure through January 31, 2010 and 35 confirmed casesas of February 9, 2010.


10/12

10

2.80

0.67

0.19

0.84

2.37

1.64

0.200.32

0.00

0.94

0.01

1.00

0.47

0.03

0.44

1.53

0.300.20

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidence

per1

000

patients



*Incidence calculated based on natalizumab exposure through December 31, 2009 and 31 confirmedcases as of January 12, 2010.


11/12

11

2.80

0.63

0.19

0.77

2.28

2.14

0.200.29

0.00

0.86

0.01

1.00

0.43

0.03

0.39

1.45

0.39

0.17

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Clinical

Trials

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidence

per1

000

patients


Based on Patients Exposed and Treatment EpochBased on Patients Exposed and Treatment EpochUpdated 30 November 2009 based on 28 cases


12/12

12

2.80

0.57

0.19

0.69

2.20

3.27

0.20 0.25

0.00

0.75

0.02

1.00

0.38

0.04

0.33

1.33

0.59

0.14

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Clinical

Trials

Post

Marketing

1-12

Infusions

13-24

Infusions

25-36

Infusions

37-48

Infusions

Incidence

per1

000

patients


Based on Patients Exposed and Treatment EpochBased on Patients Exposed and Treatment EpochUpdated 28 October 2009 based on 24 cases

historical pml by treatment epoch october 2010

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