Viramune® (nevirapine)
prolonged-release once-daily formulation for the treatment of HIV-1
infection receives CHMP recommendation for approval (not yet approved in USA)
Ingelheim, Germany, 27th July 2011
– Boehringer Ingelheim announced today that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency (EMA)
has issued a Positive Opinion recommending the approval of once-daily
Viramune® (nevirapine) prolonged-release in all member states of the
European Union.
1 The CHMP recommendation states that the new
prolonged-release tablet is indicated in combination with other
antiretroviral medications for the treatment of HIV-1 infection.
The CHMP recommendation — which includes the
once-daily, one tablet 400 mg strength for adults and adolescents and
the once-daily 50 mg and 100 mg strengths for children — follows
clinical trial results confirming the significant therapeutic benefits
of nevirapine when administered in a convenient once-a-day formulation.
2,3
In the U.S.A., the Viramune® once-daily, one tablet 400 mg
formulation was approved by the Food and Drug Administration (FDA)
earlier this year.
In clinical trials, the antiviral efficacy of the new
once-daily Viramune® prolonged-release 400mg tablet, was shown to be
non-inferior to the twice-daily immediate-release 200mg tablet,
2,3 with a safety and tolerability profile comparable to nevirapine immediate-release first approved in 1996.
Dr. Keikawus Arastéh
"Switching therapies can improve
treatment adherence, which is often key to treatment success. With
nevirapine prolonged-release, physicians and their patients can benefit
from a simplified, once-daily treatment regimen while still maintaining
the high level of efficacy, comparable tolerability, and the favourable
lipid profile inherent to the nevirapine immediate release formulation,"
commented Dr. Keikawus Arastéh, Director of Internal Medicine at
Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.
"Data has shown that the prolonged-release treatment
option combines the trusted clinical benefits of nevirapine with the
convenience of a single daily dose. Once approved in Europe, Viramune®
prolonged-release will allow an easy switch for patients currently
taking Viramune® twice-daily, and enable patients to be treated with a
regimen that fits in with today’s prescribing trends," added Professor
Klaus Dugi, MD, Corporate Senior Vice President Medicine at Boehringer
Ingelheim Headquarters
Notes to Editor:
Please be advised
This release is from Boehringer Ingelheim
Corporate Headquarters in Germany. Please be aware that there may be
national differences between countries regarding specific medical
information, including licensed uses. Please take account of this when
referring to the information provided in this document. This press
release is not intended for distribution within the U.S.A.
About Viramune®
Viramune® (nevirapine) is a product of
original research done at Boehringer Ingelheim. Nevirapine was the first
member of the non-nucleoside reverse transcriptase inhibitor (NNRTI)
class of anti-HIV drugs and is indicated for the treatment of HIV-1
infection in combination with other antiretroviral agents. This
indication is based on a principal clinical trial that demonstrated
prolonged suppression of HIV-RNA and several smaller supportive studies.
Studies have also shown that patients switching to nevirapine from a
PI-based regimen demonstrate an improved lipid profile while maintaining
viral suppression. The clinically most important adverse events
associated with nevirapine are rash and hepatic events, which have
included fatal cases. The greatest risk of severe rash and hepatic
events occurs in the first six weeks of therapy. It is essential that
patients be monitored for these reactions at all times, and intensively
during the first few months of therapy. Nevirapine should be
discontinued and not restarted following severe hepatic, skin or
hypersensitivity reactions.
About the VERxVE Study
VERxVE is a randomized, double-blind,
double-dummy, parallel group, active controlled, multinational trial
conducted to evaluate the antiviral efficacy and safety of once-daily
nevirapine 400 mg compared to twice-daily nevirapine 200 mg. A total of
1,011 adult patients were randomized to receive either nevirapine
prolonged-release or nevirapine immediate-release after a 14-day lead-in
period with nevirapine immediate-release for all patients. All patients
also received a nucleoside/nucleotide reverse transcriptase inhibitor
(NRTI) backbone of Truvada®.*
Results after 48 weeks indicated that of the patients who received
nevirapine prolonged-release in the study, 81 percent (404/505) vs. 76
percent (379/506) of patients taking nevirapine immediate-release (200
mg) achieved the study endpoint of viral load <50 copies/mL in the
week 48 + 4 window according to the primary endpoint using the Time to
Loss of Virologic Response (TLOVR) algorithm. This demonstrated
non-inferiority of nevirapine prolonged-release to nevirapine
immediate-release. In patients with an HIV-RNA >100,000 copies/mL at
baseline, the response rate was 73 percent for nevirapine
prolonged-release vs. 71 percent for nevirapine immediate-release. In
patients with baseline HIV-RNA≤100,000 copies/mL, the response rate was
85 percent for patients taking nevirapine prolonged-release compared to
79 percent for patients taking nevirapine immediate-release.
VERxVE results also showed that nevirapine
prolonged-release had a safety and tolerability profile comparable to
nevirapine immediate-release in treatment-naïve patients. After the
lead-in period, the incidence of any hepatic event was six percent for
adult patients taking nevirapine prolonged-release and nine percent for
adult patients taking nevirapine immediate-release. The rate of
symptomatic hepatic events was comparable in adult patients taking
nevirapine prolonged-release to those patients taking nevirapine
immediate-release (two percent vs. three percent).
About the TRANxITION Study
The
TRANxITION study examined the efficacy and safety of switching
virologically-suppressed patients (viral load < 50 copies/ml) from
nevirapine immediate-release 200mg twice-daily to nevirapine
prolonged-release 400mg once-daily.
TRANxITION is an open-label, parallel group, non-inferiority,
randomised study (2:1 randomisation nevirapine prolonged-release:
nevirapine immediate-release). Adult HIV-1 patients receiving nevirapine
immediate-release plus fixed-dose NRTI combinations with undetectable
viral load (VL) were enrolled. The primary endpoint was continued
virologic suppression with VL <50 copies/mL through Week 24. In the
study, 443 patients from the U.S.A. and Europe were treated; 295
switched to nevirapine prolonged-release and 148 continued on nevirapine
immediate-release. Continued virologic suppression was observed in 93.6
percent (276/295) with nevirapine prolonged-release and in 92.6 percent
(137/148) with nevirapine immediate-release at 24 weeks of follow-up.
Non-inferiority (adjusted margin of -10 percent) of nevirapine
prolonged-release to nevirapine immediate-release was demonstrated. The
rate of severe adverse events was low and comparable between both
treatment groups (3.7 percent and 4.1 percent with the prolonged-release
and immediate-release formulations respectively). The study supports
the switch from nevirapine immediate-release twice-daily to nevirapine
prolonged-release once-daily in patients who are virologically
suppressed.
Safety Information
The most common side effect of nevirapine
is rash, which can be severe or life-threatening. The most serious
adverse reactions associated with nevirapine are hepatitis, hepatic
failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, and
hypersensitivity reactions. Hepatitis/hepatic failure may be isolated or
associated with signs of hypersensitivity, which may include severe
rash or rash accompanied by fever, general malaise, fatigue, muscle or
joint aches, blisters, oral lesions, conjunctivitis (pink eye), facial
edema, eosinophilia (an abnormally high number of eosinophils in the
blood), granulocytopenia (an abnormally low concentration of
granulocytes in the blood), lymphadenopathy (swelling/enlargement of the
lymph nodes), or renal dysfunction.
About Boehringer Ingelheim
The
Boehringer Ingelheim group is one of the world’s 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 145 affiliates and more than 42,000 employees.
Since it was founded in 1885, the family-owned company has been
committed to researching, developing, manufacturing and marketing novel
products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to
act socially responsible. Involvement in social projects, caring for
employees and their families, and providing equal opportunities for all
employees form the foundation of the global operations. Mutual
cooperation and respect, as well as environmental protection and
sustainability are intrinsic factors in all of Boehringer Ingelheim’s
endeavors.
In 2010, Boehringer Ingelheim posted net sales of about
12.6 billion euro while spending almost 24% of net sales in its largest
business segment Prescription Medicines on research and development.
References
1European Medicines Agency
2Gathe J et al. Efficacy and safety of
nevirapine extended- release once daily versus nevirapine
immediate-release twice-daily in treatment-naïve HIV-1 infected
patients. Antiviral Therapy 2011;16 (epub ahead of print)
3Arastéh K et al. 24 Wk Efficacy and Safety
of Transitioning Virologically Stable HIV-1 Patients from IR Nevirapine
200 mg BID to Nevirapine XR 400 mg QD. 50th Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC), Boston, MA, USA,
September 12-15, 2010: Poster: 207
(* Truvada® is a registered trademark of Gilead Sciences, Inc.)
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