|
Pegasys
is much easier to tolerate than PegIntron, but is not stronger. Just as
we saw with PegIntron, some
patients need higher doses of Pegasys to get a >90% HCV-RNA fall per month.
As with all PegIntron and
Infergen, many patients do
not respond even with higher than normal doses.
Pegasys plus ribavirin: Is it 53% successful or 31%?
Lets look at the data from the FDA about Pegasys plus ribavirin The data are
informative about treating patients with hepatitis C. Table 1 illustrates that
young patients are easy to cure. Younger patients have less liver damage than
older patients on average since they tend to have a shorter duration of infection.
The duration of infection predicts the amount of liver fibrosis. Sixty-eight percent of patients younger than 35
years were cured, compared with only 35% of patients between 55 and 64 years
of age. Young patients have about twice the cure rate as older patients. You
cannot make conclusions about patients older than 65, because only 8 patients
were treated.
| |
Table 1. Sustained virologic response by Age |
|
| |
|
| |
Peg-IFN alfa 2a ribavirin
|
|
| |
N (%SVR) |
|
| All Patients |
453 (53) |
|
| Age (yrs): <35 |
109 (68) |
|
| 35-44 |
154 (56) |
|
| 45-54 |
136 (43) |
|
| 55-64 |
48 (35) |
|
| >65 |
8 (50) |
|
The table below illustrates that men and women have an equal chance of cure,
while cirrhosis reduces the chance of cure.
Table 2. Sustained virologic response by gender and presence or absence of
cirrhosis
| |
Peg-IFN alfa 2a ribavirin
N %SVR |
|
All Patients
|
453 (53) |
|
Gender: Men
|
324 (53) |
|
Women
|
129 (54) |
|
Cirrhosis: Present
|
56 (41) |
|
Not-Present
|
397 (55) |
|
Table three reveals a striking difference between the cure rate in US patients
compared with non US patients. The cure rate in US patients was about one third
lower than non US patients.
| |
Peg-IFN alfa 2a ribavirin
N %SVR |
|
| All patients |
453 (53) |
| US patients |
184 (42) |
|
| Non US patients |
269 (61) |
|
| |
|
|
This is very interesting. Only 41% (184/453) of the patients treated with Pegasys
plus ribavirin were from the US. These patients had only a 42% cure rate. Americans
are harder to cure than patients from other countries. This 42% cure rate is
a mix of easy to cure genotype 2 or 3 patients and the more common genotype
1 patients.
Heavier American patients have a lower success rate than lighter ones as shown
in table 4. If you weighed more than 74 kg and are American, you have about
one chance in 3 of cure. Non Americans did not show any loss of cure with higher
weight.
Table 4. Sustained virologic Response by Body Weight and by Geographic Region
| |
Total
N-SVR% |
US
N-SVR% |
Non US
N-SVR% |
| All BW |
453(53) |
184 (42) |
269(61) |
| BW <64kg |
59(66) |
0 |
59 (66) |
| <74kg |
128(62) |
40 (70)
|
88 (58) |
75-<85kg
|
117(48) |
54 (35) |
63 (59) |
85-98kg
|
104(49) |
45 (33) |
59 (61) |
>98kg
|
45(36) |
45 (36) |
0 |
------------------------------------------------------------------------
Table 5. reveals that out of 184 Americans treated with Pegasys plus ribavirin,
128 had genotype one. Only 31% of Americans with genotype one were cured. About
70% of HCV infected Americans have this genotype one strain of the virus. The
cure rate with Pegasys plus ribavirin in genotype one was not significantly
better than the cure rate with Rebetron (29%). This suggests that Pegasys plus
ribavirin is not more effective than Rebetron for most Americans-at least not
the way that these patients were treated. I think that higher doses and longer
duration of treatment may improve the poor 31% cure rate.
| |
Total
N-(%SVR) |
US
N-(%SVR) |
Non US
N-(%SVR) |
| All Subj |
453/ (53) |
184 (42) |
269 (61) |
| Genotype1
|
298(44) |
128(31) |
170(54) |
| Non-1 |
155(70) |
56(68) |
99(72) |
| Titer: low |
159(57) |
64(41) |
95(68) |
| Titer: high |
293(51) |
119(44) |
174(56) |
So what is the bottom line here? Pegasys plus ribavirin is a great drug for
non-Americans. Americans who are older, heavier and with genotype one will probably
fail standard Pegasys plus ribavirin. A 31% cure rate in genotype one
patients is equivalent to Rebetron, which cured 29% of genotype one Americans.
Just as many American patients need higher doses of PegIntron to succeed, many
need higher doses of Pegasys.
Roche and Schering Plough have not been able to
significantly improve the treatment for the majority of HCV infected Americans.
Their standard methods
cure less than one third of American patients with genotype one. Individualized
therapy with higher doses of interferon and longer duration of therapy is superior
to standard treatments. Changing to a different interferon like daily Infergen
helps some patients who do not respond to pegylated interferon.
If you are on a standard treatment, make sure you check your viral level before
treatment and about a month later. If it is not falling by at least 90% per
month, you will need to modify your treatment to have a good chance of success.
If it is falling more than 90%, check it again every 2 months.
Good luck. Ben
Cecil, MD
FDA
analysis Pegasys + Ribavirin
Pegasys
mono therapy
Pegasys
for cirrhosis
Pegasys
plus ribavirin
Details
about Pegays plus ribavirin
Pegasys
info from FDA
FDA
Pegasys transcript
Pegasys
FDA Slides | 
