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Datum nieuwsfeit: 19-01-2006
Data vergelijking van Viread en Emtriva behandeling met Combivir behandeling als onderdeel van een HIV-combinatiebehandeling gepubliceerd in New England Journal of Medicine
( BW)(CA-GILEAD-SCIENCES)(GILD) Data Comparing Viread and Emtriva to
Combivir as Part of Combination HIV Therapy Published in New England
Journal of Medicine
Business Editors/Health/Medical Writers
BIOWIRE2K
FOSTER CITY, Calif.--(BUSINESS WIRE)--Jan. 18, 2006--
Publication Describes Superior Viral Suppression
with Fewer Adverse Events Leading to Discontinuation
for Patients Taking Viread and Emtriva at 48 Weeks
Gilead Sciences, Inc. (Nasdaq:GILD) today announced the
publication of 48-week data from a clinical trial (Study 934)
comparing a once-daily treatment regimen of Viread(R) (tenofovir
disoproxil fumarate), Emtriva(R) (emtricitabine) and Sustiva(R)
(efavirenz) to a twice-daily regimen of Combivir(R)
(lamivudine/zidovudine) with Sustiva once daily in treatment-naive
patients with HIV. Data appearing in the January 19 issue of New
England Journal of Medicine (N Engl J Med 2006; 354;3, 251-260) show
that a significantly greater percentage of patients taking a regimen
containing Viread and Emtriva achieved and maintained HIV RNA less
than 400 copies/mL, with fewer side effects that resulted in study
discontinuation, and had a greater increase in CD4 cell counts
compared to patients taking a Combivir-based regimen.
Viread and Emtriva are often prescribed together as a fixed-dose
combination tablet called Truvada(R) (emtricitabine and tenofovir
disoproxil fumarate), which became commercially available after Study
934 began. Both Truvada and Combivir are widely used fixed-dose
combination medicines from the nucleoside reverse transcriptase
inhibitor (NRTI) class of antiretrovirals. NRTIs are commonly regarded
as the "backbone" of combination therapy for HIV.
"Data like these are important to help define ways for physicians
to simplify effective HIV therapy for treatment-naive patients," said
Joel Gallant, MD, Johns Hopkins University School of Medicine,
Baltimore, a lead investigator for the study and lead author of the
paper. "Even with the remarkable advances made in the field of HIV
medicine in the last 10 years, there is still a need for improved and
simplified therapy."
About Study 934
Study 934 is a Phase III, multicenter, open-label clinical trial
that enrolled 517 HIV-infected patients in the United States and
Europe. The study's primary endpoint was at 48 weeks. The prespecified
primary efficacy population included 487 patients. Participants in one
arm of the study received Viread 300 mg, Emtriva 200 mg and Sustiva
600 mg, all dosed once daily. Patients in the comparator arm received
Combivir twice daily and Sustiva 600 mg once daily. At study entry,
patients had not previously received antiretroviral therapy and had
HIV RNA (viral load) greater than 10,000 copies/mL. The study is
planned to continue through 144 weeks.
For the 48 week (n=487) primary endpoint of the study, 84 percent
of patients in the Viread/Emtriva arm compared to 73 percent of
patients in the Combivir arm achieved and maintained HIV RNA less than
400 copies/mL through week 48 using the Time to Loss of Virologic
Response algorithm (TLOVR) (p=0.002; 95% CI, +4% to +19%). Similarly,
80 percent of patients in the Viread/Emtriva arm compared to 70
percent of patients in the Combivir arm achieved and maintained HIV
RNA less than 50 copies/mL through week 48 using the TLOVR algorithm
(p=0.02; 95% CI, +2% to +17%). Patients receiving Viread/Emtriva had a
significantly greater increase from baseline in CD4 cell counts at
week 48 compared to those receiving Combivir (190 vs. 158 cells/mm3;
p=0.002; 95% CI, +9 cells/mm3 to +55 cells/mm3).
Genotypic data were collected for 35 patients with HIV that met
the criteria for resistance analyses. Resistance analysis included
patients who had HIV RNA greater than 400 copies/mL either at week 48,
or for two consecutive visits after having achieved viral suppression
below 400 copies on at least one occasion, or who discontinued prior
to week 48 but had HIV RNA greater than 400 copies mL on their last
visit prior to discontinuation. Twenty-two patients with baseline
NNRTI resistance were excluded from the analysis. There were no
significant differences between the two treatment groups, and the most
common resistance mutations that developed were associated with
Sustiva. No patient developed the K65R mutation, which is associated
with resistance to Viread.
The 48-week safety analysis for Study 934 is based on 511 patients
who received any study medication. A significantly (p=0.02) greater
percentage of patients in the Combivir group (9 percent) experienced
adverse events that resulted in the discontinuation of study
medications compared to the Viread/Emtriva arm (4 percent). The most
common cause of discontinuation related to study drug for patients in
the Combivir arm was anemia (14 patients, vs. 0 in the Viread/Emtriva
arm; p less than 0.001) and in the Viread/Emtriva arm was
NNRTI-associated rash, which occurred in 2 patients. Renal safety was
similar in the two groups and no patient discontinued study medication
due to renal events.
A significantly (p less than 0.001) greater percentage of patients
in the Viread/Emtriva arm of the study had a lower mean increase from
baseline in fasting total cholesterol levels (21 mg/dL) compared to
patients in the Combivir arm (35 mg/dL). At week 48, total limb fat
was significantly less in a subset of patients receiving Combivir
(mean of 6.9 kg or 15.2 pounds; n=49) compared to a subset of patients
receiving Viread and Emtriva (mean of 8.9 kg or 19.6 pounds; n=51;
p=0.03).
Data from Study 934 have not been reviewed by the U.S. Food and
Drug Administration (FDA). It is important that patients be aware that
individual HIV medications must be taken as part of combination
regimens, and that they do not cure HIV infection or prevent
transmitting HIV to other people.
Joint Venture to Develop Fixed-Dose Regimen of Truvada and Sustiva
On December 20, 2004, Gilead and Bristol-Myers Squibb (BMS)
announced the establishment of a U.S. joint venture to develop and
commercialize a once-daily fixed-dose combination of Truvada and
Sustiva. Gilead and BMS announced on January 9, 2006 that the
companies have obtained data supporting bioequivalence of a new
formulation of the fixed-dose combination with the components that
make up the combination and expect to file a new drug application with
the FDA in the second quarter of this year.
About HIV/AIDS
2006 marks the 25th anniversary of the start of the AIDS epidemic.
The first cases of HIV/AIDS were reported by the U.S. Centers for
Disease Control and Prevention (CDC) in the June 5, 1981 issue of the
Morbidity and Mortality Weekly Report (MMWR). Today, CDC estimates
that more than one million Americans are infected with HIV, the virus
that causes acquired immunodeficiency syndrome (AIDS). Of these,
approximately 25 percent are unaware of their infection. Although HIV
treatment options have expanded rapidly in recent years, CDC estimates
that 216,000 Americans who are HIV infected and eligible for
antiretroviral treatment are currently not receiving it.
Ensuring Access in Developing World Countries
The parent compound of Viread was discovered through a
collaborative research effort between Dr. Antonin Holy, Institute for
Organic Chemistry and Biochemistry, Academy of Sciences of the Czech
Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for
Medical Research, Katholic University in Leuven, Belgium. The
inventors have agreed to waive their right to a royalty on sales of
products containing tenofovir in the 97 developing countries served by
the Gilead Access Program to ensure the product can be offered at a
no-profit price in parts of the world where the AIDS epidemic has hit
the hardest.
Important Safety Information from U.S. Prescribing Information for
Truvada, Emtriva and Viread
Lactic acidosis and severe hepatomegaly with steatosis, including
fatal cases, have been reported with the use of nucleoside analogues
alone or in combination with other antiretrovirals. Truvada, Emtriva
and Viread are not indicated for the treatment of chronic hepatitis B
virus (HBV) infection and the safety and efficacy of these drugs has
not been established in patients co-infected with HBV and HIV. Severe
acute exacerbations of hepatitis B have been reported in patients who
have discontinued Emtriva or Viread. Hepatic function should be
monitored closely with both clinical and laboratory follow-up for at
least several months in patients who discontinue Truvada, Emtriva or
Viread and are co-infected with HIV and HBV. If appropriate,
initiation of anti-hepatitis B therapy may be warranted.
Changes in body fat have been observed in patients taking Truvada,
Emtriva and Viread and other anti-HIV medicines. The cause and long
term health effect of this condition is unknown. Immune reconstitution
syndrome has been reported in patients treated with combination
antiretroviral therapy, including Truvada, Emtriva and Viread.
About Truvada
Truvada is a fixed-dose combination of Emtriva and Viread. Truvada
combines 200 mg of emtricitabine and 300 mg of tenofovir disoproxil
fumarate in one tablet, taken once a day in combination with other
antiretroviral agents. In the United States, Truvada is indicated in
combination with other antiretroviral agents (such as non-nucleoside
reverse transcriptase inhibitors or protease inhibitors) for the
treatment of HIV-1 infection in adults. Safety and efficacy studies
using Truvada tablets or using Emtriva and Viread in combination are
ongoing.
Emtriva and Viread have each been studied as part of multi-drug
regimens and have been found to be safe and effective. In clinical
study 303 Emtriva and lamivudine (3TC) demonstrated comparable
efficacy, safety and resistance patterns as part of multidrug
regimens. These data, and those from study 903, in which lamivudine
and tenofovir were used in combination, support the use of Truvada for
the treatment of HIV-1 infection in treatment-naive adults. In
treatment-experienced patients, the use of Truvada should be guided by
laboratory testing and treatment history.
There are no study results demonstrating the effect of Truvada on
clinical progression of HIV-1, and it is not recommended that Truvada
be used as a component of a triple nucleoside regimen. Truvada should
not be used with Emtriva or Viread, or other drugs containing
lamivudine, including Combivir, Epivir(R), Epivir-HBV(R), Epzicom(TM)
or Trizivir(R). No drug interaction studies have been conducted using
Truvada. Drug interactions have been observed when didanosine,
atazanavir, or lopinavir/ritonavir are co-administered with Viread, a
component of Truvada, and dose adjustments may be necessary. Data are
not available to recommend a dose adjustment of didanosine for
patients weighing less than 60 kg. Patients on atazanavir or
lopinavir/ritonavir plus Truvada should be monitored for
Truvada-associated adverse events that may require discontinuation.
When co-administered with Viread, it is recommended that atazanavir
300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir
should not be co-administered with Viread.
Two-hundred eighty-three patients have received combination
therapy with Emtriva and Viread with either a non-nucleoside reverse
transcriptase inhibitor or protease inhibitor for 24 to 48 weeks in
ongoing clinical studies. Based on these limited data, no new patterns
of adverse events were identified and there was no increased frequency
of established toxicities. For additional safety information about
Emtriva or Viread in combination with other antiretroviral agents,
please see "About Emtriva" and "About Viread," below.
About Emtriva
In the United States, Emtriva is indicated, in combination with
other antiretroviral agents, for the treatment of HIV-1 infection in
patients over three months of age. This indication is based on
analyses of plasma HIV-1 RNA levels and CD4 cell counts from
controlled studies of 48 weeks duration in antiretroviral-naive
patients and antiretroviral-treatment-experienced patients who were
virologically suppressed on an HIV treatment regimen. In
antiretroviral-treatment-experienced patients, the use of Emtriva may
be considered for patients with HIV strains that are expected to be
susceptible to Emtriva as assessed by genotypic or phenotypic testing.
Adverse events that occurred in more than 5 percent of patients
receiving Emtriva with other antiretroviral agents in clinical trials
include abdominal pain, asthenia (weakness), headache, diarrhea,
nausea, vomiting, dizziness and rash (rash, pruritis, maculopapular
rash, urticaria, vesiculobullous rash, pustular rash and allergic
reaction). Approximately 1 percent of patients discontinued
participation because of these events. All adverse events were
reported with similar frequency in Emtriva and control treatment
groups with the exception of skin discoloration, which was reported
with higher frequency in the Emtriva treated group. Skin
discoloration, manifested by hyperpigmentation on the palms and/or
soles, was generally mild and asymptomatic. The mechanism and clinical
significance are unknown. For pediatric patients over three months of
age, the adverse event profile observed during clinical trials was
similar to that of adult patients, with the exception of anemia and a
higher frequency of hyperpigmentation.
About Viread
In the United States, Viread is indicated in combination with
other antiretroviral agents for the treatment of HIV-1 infection. This
indication is based on analyses of plasma HIV-1 RNA levels and CD4
cell counts in controlled studies of Viread in treatment-naive adults
and in treatment-experienced adults. There are no study results
demonstrating the effect of Viread on clinical progression of HIV-1.
The use of Viread should be considered for treating adult patients
with HIV-1 strains that are expected to be susceptible to tenofovir as
assessed by laboratory testing or treatment history.
Renal impairment, including cases of acute renal failure and
Fanconi syndrome (renal tubular injury with severe hypophosphatemia),
has been reported. Renal impairment occurred most often in patients
with underlying systemic or renal disease or in patients taking
concomitant nephrotoxic agents, though some cases have appeared in
patients without identified risk factors. Decreases in bone mineral
density (BMD) at the lumbar spine and hip have been seen with the use
of Viread. The clinical significance of changes in BMD and biochemical
markers is unknown and follow-up is continuing to assess long-term
impact. The most common adverse events and those occurring in more
than 5 percent of patients receiving Viread with other antiretroviral
agents in clinical trials include asthenia, pain, abdominal pain,
headache, nausea, diarrhea, vomiting, rash (rash, pruritis,
maculopapular rash, urticaria, vesiculobullous rash and pustular
rash), flatulence, dizziness and depression. Less than 1 percent of
patients discontinued participation because of gastrointestinal
events.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes innovative therapeutics in areas of unmet
medical need. The company's mission is to advance the care of patients
suffering from life-threatening diseases worldwide. Headquartered in
Foster City, California, Gilead has operations in North America,
Europe and Australia.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that the safety and efficacy data obtained through 48 weeks of
Study 934 will not be observed in other studies or clinical practice
and risks associated with the inclusion of these data in the labels
for Truvada or Viread. These risks and uncertainties could cause
actual results to differ materially from those referred to in the
forward-looking statements. Risks are described in detail in the
Gilead Annual Report on Form 10-K for the year ended December 31, 2004
and in Gilead's Quarterly Reports on Form 10-Q, all of which are on
file with the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently
available to Gilead and Gilead assumes no obligation to update any
such forward-looking statements.
For full prescribing information, please visit www.Truvada.com,
www.Viread.com and www.Emtriva.com.
Truvada, Viread and Emtriva are registered trademarks of Gilead
Sciences, Inc.
For more information on Gilead Sciences, please visit the
company's website at www.gilead.com or call Gilead Public Affairs at
1-800-GILEAD-5 or 1-650-574-3000.
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CONTACT: Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
James Loduca, 650-522-5908 (Media)