 |
|
|
| |
NEW FUZEON STUDY RESULTS: 2 years follow-up
|
| |
| |
|
|
| |
| |
 |
|
| |
| |
Reported by Jules Levin
At the Roche Fuzeon press conference here in Bangkok, Roche presented data from a survey they conducted. For every 10 patients in need of using Fuzeon, 4 of them are not offered it because their doctor decided the patient is not appropriate for the drug most likely because Fuzeon is a self-injectable and can cause injection site reactions. Perhaps these doctors feel the patient will not want to sf-inject and put up with the site reactions. But perhaps the doctor is wrong, and should not be making the decision for the patient. In addition, Roche reported the survey found that of the remaining 6 of 10 patients, three patients decide they do not want to use Fuzeon. Probably because they do not want to prepare & self-inject and perhaps also due to not wanting to experience injection site reactions. Of the three patients who do in fact start Fuzeon therapy, 1 discontinues, perhaps in part due to difficulty in administration, site reactions, or non-response. And two of the ten patients remain on fuzeon. As part of the panel at the press conference was a nurse in New Jersey who holds a regular support group which educates patients about how to administer & use Fuzeon, and provides support in initating therapy & while on therapy. He described how he is successful in getting patients who truly need to be on Fuzeon in supporting their initiation of therapy by educating them and giving emotional support. The Roche survey also found that doctors, perhaps due to time constraints, on average spend just too little time with patients suggesting that there is inadequate due consideration by the patient and the doctor in making the decision whether or not to use Fuzeon.
FUZEON 96 WEEK STUDY RESULTS
Phase III studies of Fuzeon were TORO I and II. 661 highly treatment experienced patients were randomized to receive Fuzeon plus optimized background and 334 patients were randomized to receive optimized therapy background. Treatment history of patient and resistance testing was used to select an optimized treatment background. Baseline characteristics of patients included:
--median HIV viral load: 5.2 log
--median CD4 count: 88-97 cells
--median number of prior ARVs: 12
--median years since initiating ARVs: 7
--Prior ADEs: 79-86%
--median duration of prior NRTI therapy: 6.3 yrs
--median duration of prior NNRTI therapy: 1.5 yrs
--median duration of prior PI use: 3.8-4 yrs
Data presented but not discussed in the Roche press release. Bottomline study results—
--Early response to therapy. Change from baseline at week 4 in viral load: -1.54 log for Fuzeon+OB vs --0.89 log for OB. % <400 copies/ml: 16% for Fuzeon+OB vs 9% for OB. Median time in days to 1 log or more decrease in VL from baseline: 8 days for Fyuzeon vs 92 for OB. Median time to <400 copies/ml: 99 days for Fuzeon vs not reached for OB.
--mean change in CD4 count from baseline: +166 cells for Fuzeon+OB (on-treatment) at week 96. Mean change in HIV viral load (on treatment): -2.07 log at week 96.
--at week 96, 47% of patients withdrew, and 52% remained on treatment: 10.2% for insufficient therapeutic response; 7.2% for injection site reactions; 12.1% for adverse events.
--at 96 weeks 26% of patients had <400 copies/ml ((ITT, D/C, SW or missing)). This compared with 37% at week 24, 34% at week 48. For patients who received only optimized background therapy, not Fuzeon, 16% and 13% had <400 copies at weeks 24 & 48, respectively. Patients were able to switch as soon as week 16 to add Fuzeon.
--patients with HIV RNA <50 copies over 96 weeks: Fuzeon+optimized background therapy—23% at week 24, 23% at week 48, and 17% at week 96. Patients who only received optimized background at initiatial part of study—9% had <50 copies at week 24 & 9% had <50 copies at week 48. (ITT, D/C, SW or missing)
--patients with Cd4 increase >50 cells over 96 weeks (ITT, D/C, SW or missing)—Fuzeon+optimized background: 49% at week 24, 51% at week 48, and 39% at week 96. For patients who received only optimized background, 21% at week 24 & 16% at week 48.
--patients with CD4 increase >100 cells over 96 weeks: (same ITT analysis)—patients receiving Fuzeon+OB, 30% at week 24, 38% at week 48, and 31% at week 96. Patients receiving only OB, 13% at week 24, 10% at week 48.
--upper respiratory infection: 12.2% after 1 year on therapy, year 2-7.1%, total-19%. Pneumonia 2.7% after 1 year on Fuzeon, 1.2% year 2, 3% total. Fatigue: 20% year 1, 3.3% year 2, 24% total.
--injection site reactions: 70-80% of patients reported mild tenderness, 20% moderate pain, a few percent severe pain—analgesics required or limited usual activities.
PATIENTS WHO SWITCHED FROM OB ARM TO FUZEON + OB ARM (Switch Patients)
Switch Patients:
Patients failing on OB arm were permitted to switch to a Fuzeon containing regimen at virologic failure (after week 8) or at week 48. Reptimization of OB was permitted. Median time to switch 16 weeks.
MEAN HIV RNA CHANGE FROM ORIGINAL BASELINE
Switch Patients: about 1 log HIV viral load reduction at week 96 from baseline
Fuzeon+OB: about 2 log reduction in VL at week 96 from baseline
MEAN CD4 CELL COUNT CHANGE FROM ORIGINAL BASELINE
Switch patients: increase of about 100 cells at week 96 from baseline
Fuzeon plus OB: about 166 cell increase from baseline to week 96
PATIENT DISPOSITION AT WEEK 96
Fuzeon/OB OB
|
|
|
Switch to FUZ/OB
|
|
|
|
No
|
Yes
|
|
|
|
N=104
|
n=230
|
|
Total # withdrawn
|
47%
|
39%
|
50%
|
|
adverse events
|
12%
|
11%
|
9%
|
|
injection site reaction
|
7%
|
0%
|
9%
|
|
death
|
<1%
|
<1%
|
1.7%
|
|
lab test abnorm
|
<1%
|
0
|
0
|
|
Admin/other
|
10%
|
1.9%
|
6.5%
|
|
Insuf therapy response
|
10%
|
12%
|
16%
|
|
Refused treatment
|
6%
|
10%
|
5%
|
|
Failure to return
|
1%
|
1.6%
|
1%
|
ADVERSE EVENTS (related & unrelated BETWEEN WEEKS 48 & 96 (Fuzeon+OB)
Comparing adverse events incidence in year 1 to year 2, you see less patients experiencing these events. This is likely due to constitutional systemic improvement due to improved CD4s & viral load.
| Year 1 | Year 2 | Total | | Upper respiratory tract infection | 12% | 7% | 19% | | Sinusitis | 8% | 3% | 11% | | Bronchitis | 7.6% | 3% | 10.7% | | Cough | 8.7% | 3% | 12.7% | | Diarrhea | 32% | 5% | 37% | | Pyrexia | 12% | 4% | 17% | | Arthralgia | 8% | 3% | 11% | | Oral candidiasis | 8% | 3% | 11% | | Fatigue | 20% | 3% | 24% | | Dermatitis | 10% | 3% | 12% |
The presenter suggested that the data above supports not waiting too long to initiate Fuzeon. Cd4 increase & viral load response was reduced in patients who deferred Fuzeon due to randomization in the study. The presenter is suggesting that as you accumulate more drug resistance and the available drugs are not as effective the addition of Fuzeon is less effective. It is important to have new drugs that are effective to start along with Fuzeon. Data shows that using Kaletra improves response to Fuzeon. In the tipranavir studies researchers are examining if patients who used Fuzeon plus tipranavir did better than patients who did not use tipranavir. That data should be available in the Fall 2004.
|
| |
|
|
|
|
|
