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FDA
Approves Roche Protease Inhibitor Invirase Boosted with Norvir
Roche’s
HIV protease inhibitor Invirase (saquinavir hard gel) won approval
on January 6, 2004 for sale in the US as an HIV treatment in combination
with low dose (100mg) Norvir (ritonavir) from Abbott Laboratories.
This new dosing regimen boosts blood levels of saquinavir to allow
for twice-daily dosing and overcomes the inadequate drug levels
associated with use of Invirase alone.
In
a press release, Roche said the US Food and Drug Administration
approved the combination treatment that uses 1,000 milligrams of
Invirase and 100mg of ritonavir twice daily.
The
FDA based its decision on studies concerning Roche's other protease
inhibitor, Fortovase (saquinavir soft gel), at 1,200 milligrams.
Roche said the studies indicated that Invirase and Fortovase, separately
combined with ritonavir, maintained similar levels of active inhibitors
in a patient's blood.
A
Roche spokeswoman said the use of Invirase as a combination treatment
presents several advantages over combination Fortovase therapy.
She said the combined use of Invirase and ritonavir led to fewer
gastrointestinal side effects than Fortovase plus ritonavir. In
addition, she added that twice-a-day Invirase does not require refrigeration,
unlike Fortovase. In addition, Fortovase is administered three times
each day.
Roche
is developing a 500-milligram dose of Invirase and expects to file
with the FDA for approval of that formulation sometime this year.
“The approval
of Invirase for boosted dosing is another important step in Roche’s
ongoing efforts to define the optimal use of saquinavir, which was
developed from our company’s laboratories as the first protease
inhibitor for HIV,” said Kathy Presto, Vice President, US HIV Franchise,
Roche. “We have invested significantly in clinical trials and will
continue our commitment through development of the Invirase 500
mg tablet formulation.”
Following
is the text of the Roche press release on the approval of combination
Invirase 1000mg / ritonavir100mg:
On
January 6, 2004 Roche announced U.S. Food and Drug Administration
(FDA) approval of its protease inhibitor INVIRASE® (saquinavir mesylate 1000 mg) for use with ritonavir
(100 mg) in combination regimens for the treatment of HIV infection.
This new dosing strategy increases (“boosts”) blood levels of saquinavir
to enable twice-daily dosing and eliminates the inadequate drug
levels associated with use of INVIRASE alone.
FDA
approval of Roche’s supplemental New Drug Application (sNDA) for
INVIRASE was based on data which showed that INVIRASE 1000 mg with
ritonavir 100 mg twice-daily provides similar to or greater levels
of saquinavir over a 24-hour period than those achieved with another
formulation of saquinavir, Fortovase®, 1200 mg three times
per day.
Fortovase
with ritonavir was studied in a heterogeneous population of 148
HIV-infected patients. Results showed that 91 of 148 subjects (61
percent) achieved and/or sustained an undetectable HIV RNA levels
(<400 copies/mL) at the completion of 48 weeks of treatment.
The efficacy of INVIRASE with ritonavir or Fortovase (with or without
ritonavir co-administration) has not been compared against the efficacy
of antiretroviral regimens currently considered standard of care.
“INVIRASE with
ritonavir is an attractive option for the treatment of HIV because
it is designed to provide consistently therapeutic levels of saquinavir
with twice-daily dosing,” said Dr. Frank Palella, Assistant Professor
of Medicine, Feinberg School of Medicine, Northwestern University,
Chicago. “With saquinavir, physicians and patients have the benefit
of eight years of clinical experience on which to base treatment
decisions. Today’s news confirms that only low, 100 mg doses of
ritonavir are needed to achieve effective levels of saquinavir when
given with 1000 mg INVIRASE.”
INVIRASE capsules
do not require refrigeration and are smaller in size than Fortovase
capsules. Roche is developing a 500 mg formulation of INVIRASE,
designed to be used in the new boosted dosing regimen, that will
cut daily pill count in half. A filing for the 500 mg formulation
is projected for submission to the FDA for review in 2004.
It
is important to note that INVIRASE and Fortovase are not bioequivalent
and cannot be used interchangeably. INVIRASE may be used only if
it is to be combined with ritonavir, which significantly inhibits
saquinavir’s metabolism and provides plasma saquinavir levels at
least equal to those achieved with Fortovase. Fortovase is the
recommended formulation when using saquinavir as the sole protease
inhibitor in an antiviral regimen.
Dosing of Boosted INVIRASE
The FDA-approved dosing for boosted INVIRASE is 1000 mg of INVIRASE
(5 x 200 mg capsules) in combination with ritonavir 100 mg, twice
a day. Ritonavir should be taken at the same time as INVIRASE.
INVIRASE and ritonavir should be taken within 2 hours after a meal.
01/07/04
Sources
“US
FDA approves Invirase boosted with ritonavir for use in treatment
of HIV/AIDS." Press Release. January 6, 2004.
Dow
Jones Newswires. January 6, 2004.
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