Natalizumab PML Incidence Estimates

by Treatment Epoch
3.0
2.80

2.5
Incidence per 1000 patients

2.0 1.95

1.71
1.5 1.44

1.15
1.0 1.00 1.03
0.91 0.93
0.71
0.60
0.5 0.45
0.38
0.23
0.20
0.07
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials* Marketing Infusions Infusions Infusions Infusions
*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 of
October 1, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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 and therefore having risk of developing PML during this time). 1
Natalizumab PML Incidence Estimates
by Treatment Epoch
3.0
2.80

2.5
Incidence per 1000 patients

2.0 1.98

1.72

1.5 1.46

1.14
1.0 1.00 1.04
0.90 0.91
0.70
0.62
0.5 0.42
0.39
0.23
0.20
0.07
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials* Marketing Infusions Infusions Infusions Infusions
*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 August 31, 2010 and 68 confirmed cases as of
September 2, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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). 2
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.0 1.92

1.59
1.5
1.39

1.09
1.0 1.00 0.98
0.85
0.77
0.65 0.63
0.5
0.40
0.24 0.31
0.20
0.08
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials* Marketing Infusions Infusions Infusions Infusions
*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 July 31, 2010 and 63 confirmed cases as of
August 4, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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 and therefore having risk of developing PML during this time). 3
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.0 1.97

1.61
1.5 1.42

1.0 1.00 1.03 0.99

0.80
0.74
0.61 0.60
0.5
0.37
0.21 0.27
0.20
0.08
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials* Marketing Infusions Infusions Infusions Infusions

*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 of
July 2, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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 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 the
confidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing the denominator of treated patients will
increase the precision of the estimates and narrow the confidence interval. There are limited data beyond three years of treatment. 4
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.05
2.0

1.62
1.5 1.47

1.0 1.00 1.00 1.02

0.77
0.70
0.58 0.58
0.5
0.35
0.20 0.20 0.23
0.08
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials* Marketing Infusions Infusions Infusions Infusions

*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 of
June 7, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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 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 the
confidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing the denominator of treated patients will
increase the precision of the estimates and narrow the confidence interval. There are limited data beyond three years of treatment. 5
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 Patients

2.0 1.97
1.85

1.5
1.38

1.0 1.00
0.92 0.93
0.79
0.70
0.5 0.52 0.54
0.32 0.26
0.20 0.17
0.08
0.0 0.00 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions

*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through April 30, 2010 and 49 confirmed cases as of
May 6, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients exposed to
TYSABRI (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 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 the
confidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing the denominator of treated patients will
increase the precision of the estimates and narrow the confidence interval. There are limited data beyond three years of treatment.
6
 Natalizumab PML Incidence Estimates
by Treatment Epoch
3.0
2.80

2.5
Incidence per 1000 patients

2.08
2.0 1.94

1.5
1.33

1.0 1.00
0.89 0.88 0.89
0.67
0.56
0.5 0.49
0.33 0.29
0.20 0.17
0.08
0.0 0.00 0.01
Clinical Post 1-12 13-24 25-36 37-48
Trials Marketing Infusions Infusions Infusions Infusions

*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through March 31, 2010 and 46 confirmed cases
as of April 6, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of patients
exposed to TYSABRI (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 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 an
indication of the precision of the estimate. The wider the confidence intervals in relation to the point estimate indicate a higher level of
uncertainty. Increasing the denominator of treated patients will increase the precision of the estimates and narrow the confidence
interval. 7
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.0 2.00
1.81

1.5
1.36

1.0 1.00
0.83 0.89

0.62 0.62
0.5 0.54
0.44
0.31
0.20 0.16
0.08 0.13
0.0 0.00 0.02

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions

*Incidence estimates by treatment epoch are calculated based on TYSABRI exposure through February 28, 2010 and 42 confirmed
cases as of March 10, 2010. The incidence for each epoch is calculated as the number of PML cases divided by the number of
patients exposed to TYSABRI (e.g. for 25 to 36 infusions all PML cases diagnosed during this period is divided by the total number of
patients 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 the
estimate. The wider the confidence intervals in relation to the point estimate indicate a higher level of uncertainty. Increasing the
denominator of treated patients will increase the precision of the estimates and narrow the confidence interval.
8
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.38

2.0
1.76
1.56
1.5

1.0 1.00 0.97 0.96

0.73
0.52 0.54
0.5 0.49
0.36 0.27
0.20 0.19
0.03 0.06
0.0 0.00

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions

Incidence calculated based on natalizumab exposure through January 31, 2010 and 35 confirmed cases
as of February 9, 2010. 9
 Natalizumab PML Incidence Estimates
by Treatment Epoch

3.0
2.80

2.5
Incidence per 1000 patients

2.37

2.0

1.64
1.5 1.53

1.0 1.00
0.94
0.84
0.67
0.5 0.47 0.44
0.32 0.30
0.20 0.19 0.20

0.0 0.00 0.03 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions
*Incidence calculated based on natalizumab exposure through December 31, 2009 and 31 confirmed
cases as of January 12, 2010. 10
 Natalizumab PML Incidence Estimates
Based on Patients Exposed and Treatment Epoch
Updated 30 November 2009 based on 28 cases

3.0
2.80

2.5
Incidence per 1000 patients

2.28
2.14
2.0

1.5 1.45

1.0 1.00
0.86
0.77
0.63
0.5 0.43 0.39 0.39
0.29
0.20 0.19 0.17
0.0 0.00 0.03 0.01

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions

11
 Natalizumab PML Incidence Estimates
Based on Patients Exposed and Treatment Epoch
Updated 28 October 2009 based on 24 cases

3.5
3.27

3.0
Incidence per 1000 patients

2.80

2.5
2.20
2.0

1.5
1.33

1.0 1.00

0.69 0.75
0.57 0.59
0.5
0.38 0.33
0.20 0.25 0.19 0.14
0.0 0.00 0.04 0.02

Clinical Post 1-12 13-24 25-36 37-48

Trials Marketing Infusions Infusions Infusions Infusions

12