European Commission Approves Tipranavir for Treatment of HIV in
Multi-drug Resistant HIV Patients
The
European Commission has approved the protease
inhibitor tipranavir (Aptivus) in combination with
low dose ritonavir
and other antiretroviral agents for the treatment of HIV in combination.
Following is the text of the approval announcement from drug maker
Boehringer Ingelheim:
Aptivus,
a non-peptidic protease inhibitor, co-administered with low-dose
ritonavir is indicated for combination antiretroviral treatment
of HIV-1 infection in highly pre-treated adult patients with virus
resistant to multiple protease inhibitors (PIs).
This
authorization was based on exceptional circumstances given that
HIV/AIDS is a life-threatening illness with a need for rapid access
to new treatment options.
The approved dose of Aptivus is 500 mg taken with 200 mg of ritonavir,
twice daily. Co-administration with ritonavir is required and
“boosts” the therapeutic levels of Aptivus.
Aptivus
250 mg soft gel capsules will become available in the various
countries of the European Union as soon as the necessary pricing
and reimbursement approvals have been achieved.
Aptivus
was approved for use in the U.S.
on June 22, 2005, in Mexico
on July 19, 2005, and in Switzerland
on
August 26, 2005, and is currently under review by other regulatory
agencies.
Aptivus works by blocking protease, an enzyme needed to complete
the HIV replication process. Aptivus is able to enter infected
immune cells and inhibit HIV replication for many strains of HIV
that are resistant to other commercially available PIs.
In two large-scale clinical trials, Aptivus was shown to be effective
in treating HIV patients whose virus has developed resistance
to other therapies. These studies showed that Aptivus was more
effective in treating drug resistant HIV than other commonly used
ritonavir-boosted
PIs, including Kaletra®
(lopinavir/r), Invirase®
(saquinavir), Agenerase®
(amprenavir) and Crixivan®
(indinavir).
“With the advent of drugs to treat HIV, patients are living longer.
However, they continue to face challenging health issues, such
as the development of resistance to available anti-HIV drugs,”
said Dr. Andreas Barner, member of the Board of Managing Directors
of Boehringer Ingelheim and responsible for Research, Development
and Medicine. “The research and development of innovative new
therapies such as Aptivus is imperative for the successful treatment
of HIV and we are proud that Aptivus is a significant breakthrough
for the many patients who need an effective new treatment option
to help manage their disease.”
Drug
resistance is one of the major challenges that patients and physicians
face in the treatment of HIV. Resistance develops when the virus
mutates and is no longer suppressed by drugs that were once effective.
A recent 6-year study demonstrated a high prevalence of drug-resistant
virus in a European cohort of patients under treatment for HIV-1
infection. Additionally, U.K. data indicate
that transmission of drug-resistant virus is on the rise.
Pivotal Data
Data
from two large-scale clinical studies on tipranavir involving
more than 1,400 patients (RESIST-1
and RESIST-2) formed the foundation of the marketing
authorization approval by the EMEA. These trials examined the
treatment response of Aptivus boosted with ritonavir versus a
comparator group in which patients received one of several marketed
ritonavir-boosted PIs.
Investigators
selected a comparator PI that offered patients the best opportunity
for treatment response based on resistance testing and their prior
treatment history. The comparator PIs were lopinavir, indinavir,
saquinavir and amprenavir
(Agenerase). In addition, patients in both arms
received an optimized background regimen of other antiretroviral
drugs.
The results of the RESIST studies demonstrated that a statistically
significant greater percentage of HIV-positive patients taking
Aptivus boosted with ritonavir achieved a treatment response versus
the comparator group (40% vs. 18%). Treatment response was defined
as a confirmed 1 log10 or greater decrease in viral load from
baseline.
In addition, a significantly greater proportion of patients receiving
regimens that contain boosted Aptivus were able to reduce the
amount of HIV in their blood to undetectable levels than in the
boosted comparator group (<400 copies/ml: 34% vs. 15%). Patients
treated with Aptivus boosted with ritonavir also experienced greater
increases in their immune cells than those treated with a ritonavir-boosted
comparator PI (34 cells vs. 4).
Aptivus
Aptivus,
a new non-peptidic protease inhibitor, works by inhibiting protease,
an enzyme needed to complete the HIV replication process. Based
on available clinical and in vitro data, Aptivus is active against
most strains of HIV-1 that are resistant to commercially available
protease inhibitors. The safety and efficacy of Aptivus in pediatric
patients or in adult patients who have not previously taken anti-HIV
medications have not been established. Phase 2 and 3 studies in
these populations are fully enrolled and ongoing.
In
studies to date, Aptivus has been well tolerated by most patients
and has a safety profile similar to other PIs. The most commonly
reported side effects of at least moderate intensity in patients
enrolled in the RESIST studies taking Aptivus/r are gastrointestinal,
including diarrhea, nausea, vomiting and abdominal pain. Fever,
fatigue, headache, bronchitis, depression and rash also occurred.
Aptivus boosted with low-dose ritonavir has been associated with
reports of hepatic adverse events, which have included some fatalities.
Extra vigilance is warranted in patients with chronic
hepatitis B or hepatitis
C co-infection, as these patients have an increased
risk of liver toxicity. The most common moderate to severe laboratory
abnormalities were elevated liver enzymes and elevated lipid levels.
Most laboratory abnormalities were asymptomatic and most patients
were successfully treated without discontinuation.
Aptivus does not cure HIV infection/AIDS or prevent the transmission
of HIV to others. Patients may continue to develop opportunistic
infections and other complications associated with HIV disease.
Tipranavir:
An Overview
HIV
and Hepatitis.com Articles on Tipranavir
10/28/05
Sources
Boehringer Ingelheim`s
global website on HIV/AIDS
Boehringer
Ingelheim. EU commission approves Aptivus® for the treatment of
HIV. Press Release. October 26, 2005.
