 |
|
|
| |
FUZEON & FOSAMPRENAVIR STUDY RESULTS
|
| |
| |
|
|
| |
| |
 |
|
| |
| |
Reported by Jules Levin
FUZEON, (96-week study Results) & Fosamprenavir ('908') 48 Week results in PI-Experienced
At Monday's first oral HIV session, presentations were made on 48-week study results comparing fosamprenavir/ritonavir to Kaletra (CONEXT Study) and a second study on 96-week results for Fuzeon (TORO I & II). Here are the press releases from Roche & GSK/Vertex discussing the study results, as I think you would like to see the data as quickly as possible. As soon as I get a chance I will write & distribute my reports but by glancing through these press releases the data presented at the conference appears accurate in the press releases. Regarding the fosamprenavir study, the presenter said as I recall the statistical analysis did not find fosamprenavir to be non-inferior & did not find Kaletra to be superior.
FUZEON 96 WEEK STUDY RESULTS
Data presented but not discussed in the Roche press release. Bottomline study results—
--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.
New Data Finds Fuzeon-Based Therapy Provides Significant Long-Term Benefit
AIDS Survivor Demonstrates Benefits of HIV Fusion Inhibitor --
BANGKOK, THAILAND (July 12, 2004) -- Fuzeon® (enfuvirtide), the first and only fusion inhibitor for the treatment of HIV, durably suppresses HIV and provides continuous increases in immune (CD4) cells over a period of 96 weeks, according to new data presented today at the XV International AIDS Conference (IAC). In another key study finding, more than half of treatment-experienced patients (56 percent) who began using Fuzeon at the outset of the study were successful in completing 96 weeks of treatment. Additionally, investigators reported no late-emerging safety issues associated with the longterm use of Fuzeon.
"The new data show that the significant virological and immunological benefits of Fuzeon seen in earlier analyses are extended to 96 weeks, an especially notable achievement given the extensive prior drug exposure of patients enrolled in the TORO studies," said Corklin Steinhart M.D., Senior Attending Physician, Mercy Hospital, Miami, FL. "It is particularly exciting that more than half of patients who began treatment with Fuzeon continued on the drug for 96 weeks. This news, coupled with the positive 96-week safety analysis, should be encouraging to patients who are considering Fuzeon as a long-term treatment option."
The high prevalence of HIV drug resistance among patients in the U.S. highlights the need for newer HIV drugs, like Fuzeon, that are active against drug-resistant virus. Data recently presented at the XII International Drug Resistance Workshop, from a large cohort of HIV-infected individuals prescribed antiretroviral therapy from 2001-2003, showed that four out of five of those tested had resistance to at least one anti-HIV drug.1 Thirty-nine percent were found to have resistance to a drug in two classes, and 18 percent had resistance to a drug in three classes. These data are consistent with previous findings from a different study recently published in AIDS by Dr. Douglas Richman, which showed that 76 percent of US patients with measurable viral load in 1996-1998 carried a strain of the virus that is resistant to at least one drug.2
Fuzeon Patient Treated for Three Years Helps Demonstrate Long-Term Efficacy
Richard Apodaca -- a 62 year-old AIDS survivor who had exhausted most of his treatment options and was beginning to lose hope before enrolling in a clinical trial for Fuzeon more than three years ago -- provides evidence that patients can continue to experience significant long-term benefits from Fuzeon. Richard's immune cells had dropped into the single digits and his viral load soared into the millions. A participant in an earlier trial for Fuzeon, Richard began to see these numbers improve shortly after initiating combination therapy with Fuzeon. "Four years ago, HIV had decimated my immune system. After beginning treatment with Fuzeon and other anti-HIV drugs, my viral load became undetectable, and my CD4 count increased dramatically. Currently my viral load is undetectable and I have a CD4 count of over 350," said Richard.
Today Richard is leading a full and healthy life. He is an HIV/AIDS advocate who is involved with the Names Project and collects HIV medications for patients in developing countries. He has also adopted two African children suffering from AIDS. Richard is an avid runner who has participated in 13 marathons throughout the world, including those in New York City, Prague, and Hawaii, all while continuing to adhere to his Fuzeon-based regimen.
Delayed Initiation of Fuzeon May Compromise Response
The data presented at IAC were from a 96-week analysis of the TORO studies, two randomized, open-label trials that together enrolled approximately 1,000 HIV infected patients who had previously been treated with an average of 12 antiretrovirals. Patients were randomized to receive a regimen of anti-HIV drugs with or without Fuzeon. Patients randomized not to receive Fuzeon were allowed to add Fuzeon to their regimens after week eight if they met virological failure criteria or at the 48 week timepoint.
Patients who were randomized to receive a Fuzeon-based regimen had significantly lower levels of the virus and higher CD4 counts at 96 weeks compared with those randomized to a regimen without Fuzeon. Patients originally in the non-Fuzeon control arm who were later switched to Fuzeon (after virological failure) showed a mean reduction in viral load at week 96 of 1.1 log10 copies/mL, compared to a 2.1 log10 copies/mL mean reduction for patients randomized to the Fuzeon arm -- thereby highlighting the potential consequences of delaying the initiation of treatment with Fuzeon.
Patients in the Fuzeon arm saw continuous improvements in CD4 cells over the study period, with the mean CD4 increase from baseline of 166 cells/mm3 at week 96. In contrast, patients who used Fuzeon after switching from a non-Fuzeon regimen, experienced a mean increase of 116 cells/mm3 from baseline at week 96.
96-Week Safety
No new safety issues were identified in the 96-week analysis, and there was no evidence of long-term or cumulative toxicities. Rather, patients in the Fuzeon arm experienced less diarrhea, nausea and fatigue, side effects often associated with antiretroviral therapy. Injection site reactions, which were found to not increase in severity over 96 weeks, are the most common adverse event associated with use of Fuzeon.
Adherence to Fuzeon-Based Regimens at 48 Weeks
In a separate poster presentation at IAC, adherence to Fuzeon-based regimens was found to be high, and similar to adherence rates among patients taking a regimen of oral drugs only. Furthermore, adherence to Fuzeon-based regimens was not influenced by baseline disease status, treatment history or prior intravenous drug use. For more information on Fuzeon, patients and physicians can visit www.Fuzeon.com or call 1-877-4FUZEON.
Facts About FUZEON
Fuzeon was granted accelerated approval on the basis of 24-week data by the U.S. Food and Drug Administration in March 2003, and is also approved in the European Union, Switzerland and Canada. Fuzeon leads the first class of anti-HIV drugs with a unique mechanism of action to be introduced in seven years. Unlike other HIV drugs that work after HIV has entered the human immune cell, Fuzeon works outside the CD4 cell, blocking HIV from entering the cell. For this reason, Fuzeon is effective in treatment-experienced patients who have developed resistance to other anti-HIV drugs, though patients may still develop resistance to Fuzeon.
Fuzeon (enfuvirtide) in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of Fuzeon of 24 weeks' duration. Subjects enrolled were treatmentexperienced adults; many had advanced disease. There are no studies of Fuzeon in antiretroviral-naïve patients. There are no results from controlled trials evaluating the effect of Fuzeon on clinical progression of HIV-1.
Injection Site Reactions (ISRs):
ISRs are the most common adverse events associated with Fuzeon. In two controlled Phase III studies at 24 weeks, TORO 1 and TORO 2, 98 percent of patients had at least one local injection site reaction. Signs/symptoms may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis. Nine percent of patients had local reactions that required analgesics or limited usual activities.
Pneumonia:
An increased rate of bacterial pneumonia was observed in subjects treated with Fuzeon in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to Fuzeon use. Patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia. Risk factors for pneumonia included low initial CD4 cell count, high initial viral load, intravenous drug use, smoking and a prior history of lung disease.
Hypersensitivity Reactions:
Hypersensitivity reactions have been associated with Fuzeon therapy and may recur on rechallenge. Hypersensitivity reactions have included individually and in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension and elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving Fuzeon include primary immune complex reaction, respiratory distress, glomerulonephritis and Guillain-Barre syndrome.
------------------
Vertex Press Release: 48-Wk Data for Lexiva/r in PI- Experienced Pts Presented at IAC
The following press release was issued today:
Study Evaluates Effectiveness of LEXIVA/ritonavir and Lopinavir/ritonavir in Protease Inhibitor (PI) - Experienced Patients
48-Week Data Presented at IAC
BANGKOK, July 12 /PRNewswire-FirstCall/ -- HIV treatment regimens containing the protease inhibitor (PI) LEXIVA(R) (fosamprenavir calcium) dosed with ritonavir (LEXIVA/r) or lopinavir (LPV) and ritonavir (LPV/r) were effective in suppressing HIV in patients who had failed prior PI-containing regimens, according to information presented here today at the International AIDS Conference (IAC). Lexiva was co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals (Nasdaq: VRTX). The data are based on 48-week results of the CONTEXT study, a Phase III clinical trial that enrolled patients who had experienced virologic failure (VF) while receiving one to two prior PI regimens. Patients were randomized to take one 700mg LEXIVA tablet and one 100mg capsule of ritonavir (LEXIVA/r) twice a day (BID) (four capsules daily), 1400mg Lexiva plus 200mg ritonavir once a day (QD), or three LPV/r capsules, each combining 400mg LPV and 100mg of ritonavir BID (six capsules daily). PIs were taken in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). LEXIVA is indicated for the treatment of HIV infection in adults in combination with other antiretroviral medications. The following points should be considered when initiating therapy with LEXIVA/r in PI-experienced patients: the PI-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/r and LPV/r are clinically equivalent. Once-daily administration of LEXIVA dosed with ritonavir is not recommended for PI-experienced patients, who are advised to take one 700mg tablet of LEXIVA BID in combination with one 100mg capsule of ritonavir BID. At 48-weeks, 58 percent (62 of 107 patients) taking LEXIVA/r BID achieved viral loads (VL) below 400 copies/mL, and 46 percent (49) had VL below 50 copies/mL. Of 103 patients who took LPV/r BID, 61 percent (63) achieved VL below 400 copies/mL and 50 percent (52) had VL below 50 copies/mL. At baseline, patients in both treatment arms had similar viral loads, CD4 cell counts, and PI-associated resistance mutations. Prior NRTI experience and the presence of RT-associated mutations, however, were higher at baseline in patients who subsequently were randomized to the study arm that included LEXIVA/r compared to the group assigned to the study arm containing LPV/r. There was a higher incidence of NRTI mutations in the LEXIVA/r BID group (mean 1.7) compared to the group taking LPV/r BID (1.4). This was primarily due to a higher number of subjects harboring virus with three or more thymidine analogue mutations (TAMS) in the LEXIVA/r BID group (38 percent), compared to 24 percent in the group taking LPV/r BID. "There was no difference between the LEXIVA/r BID and lopinavir/r BID study arms in the proportion of patients with virologic failure with 29 percent versus 27 percent respectively," said Edwin DeJesus, M.D., Infectious Disease Consultants, Altamonte Springs, FL. Mutations Present at Baseline The most common protease-associated resistance mutations seen at baseline among the 210 patients included in the study were:
* L90M in 63 patients (30 percent)
* M46I/L in 48 patients (23 percent)
* D30N in 45 patients (21 percent)
"There was no significant difference between the two study arms in the virologic responses of patients who had these mutations present at baseline," said Rob Elston, GSK scientist and study presenter. Viral suppression in the presence of L90M was achieved in 16 of 31 patients (52 percent) taking LEXIVA/r, and in 17 of 28 patients (61 percent) taking LPV/r. Among patients with M46I/L mutations, 11 of 22 (50 percent) taking LEXIVA/r and 12 of 24 (50 percent) taking LPV/r responded to treatment, while 21 of 22 patients (95 percent) with D30N mutations responded in the arm containing LEXIVA/r compared to 17 of 18 (94 percent) in the arm containing LPV/r. Varying degrees of cross-resistance among HIV-1 protease inhibitors have been observed. Because the potential for HIV cross-resistance among protease inhibitors has not been fully explored, it is unknown what effect therapy with LEXIVA will have on the activity of subsequently administered protease inhibitors. Clinical relevance of resistance data is currently being evaluated.
Important Safety Information about LEXIVA HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to others. LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir. Hyperglycemia, new onset or exacerbations of diabetes mellitus, and spontaneous bleeding in hemophiliacs have been reported with protease inhibitors. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown. LEXIVA is contraindicated with ergot derivatives, cisapride, pimozide, midazolam, and triazolam. If LEXIVA is coadministered with ritonavir, flecainide and propafenone are also contraindicated. Treatment with LEXIVA and ritonavir has resulted in the increase in concentration of triglycerides.
The most common adverse events seen in clinical trials with LEXIVA were diarrhea, nausea, vomiting, headache and rash.
SOURCE Vertex Pharmaceuticals
|
| |
|
|
|
|
|
