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Tibotec Offers Expanded Access Program (EAP)
for Experimental Protease Inhibitor TMC 114 and Announces Plan to
Seek FDA Accelerated Approval of the Drug
 Tibotec,
a subsidiary of pharmaceutical giant Johnson & Johnson, announced
this week that the company plans to start an expanded access program
(EAP) for its experimental
protease inhibitor (PI) TMC114 in the fall of 2005.
EAPs provide promising experimental drugs free to people with AIDS
who have exhausted the benefits of all existing therapies and have
no other viable treatment options.
TMC114 is highly active in vitro
against HIV with PI
resistance mutations and against PI-resistant clinical
isolates. The promising virology profile of the drug is the result
of its unique chemical structure: a highly flexible molecule that
can adapt itself to the changing shape of HIV mutants.
Initiation
of enrollment into the expanded access program -- which will be
for heavily treatment-experienced adults living with HIV/AIDS --
is contingent on the approval of local health authorities and recruitment
of pivotal phase III trials. The initial EAP is expected to enroll
patients this summer at approximately 30 sites. The principal criteria
for the forthcoming EAP will be HIV viral load >10,000 copies/mL,
<100 CD4 cells and no viable treatment options.
A second phase
of the EAP in the fall of this year will enroll patients at approximately
200 sites worldwide “We know that many people living with HIV/AIDS
have run out of treatment options because of the increasingly significant
issue of viral resistance, and we are working to provide them with
access to TMC114 as soon as possible through this program,” said
Paul Stoffels, M.D., President of Tibotec.
Submission
to FDA for Accelerated Approval of TMC 114
Tibotec also
announced this week that it plans to seek accelerated (fast track)
approval for TMC114 in the United States and Europe through regulatory
applications filed by early 2006. These filings will be based primarily
on the 24-week primary results of the company’s two phase IIB trials.
After the filing, the FDA will approve or reject the application
within 180 days (6 months).
Data from a
24-week combined interim analysis of the phase IIB trials of TMC114
that were presented at the 12th
Conference on Retroviruses and Opportunistic Infections (12thCROI)
will be used as the basis for seeking accelerated approval.
That analysis
included two phase IIB (dose-finding), randomized trials of TMC114
boosted with ritonavir (TMC114/RTV) in patients with
experience of at least three classes of antiretrovirals and with
one or more primary protease inhibitor mutations.
Patients in
the highest dose group, 600mg/100mg BID, experienced a mean reduction
in plasma HIV RNA of -1.85 log10, compared to a reduction
of - 0.27 log10 in the control group. Patients were
randomized to receive optimized background regimen (OBR) plus one
of four doses of TMC114/RTV (400mg/100mg QD; 800mg/100mg QD; 400mg/100mg
BID; 600mg/100mg BID) or optimized background regimen (OBR) plus
investigator-selected control protease inhibitor(s).
The interim analysis was performed
after 150 patients had reached 24 weeks in each of the two studies;
a total of 497 patients were included in the analysis.
After 24 weeks,
the percentage of patients reaching undetectable virus levels (<50
copies/ml) ranged from 30% (lowest dose group) to 47% (highest dose
group) in the TMC114/RTV arms, compared with 10% in the control
arm.
The most common
adverse
events were headache and diarrhea, which were 17%
and 14% respectively across all TMC114/RTV arms compared with 23%
and 20% in the control arm. These studies will continue to 144
weeks.
Based
on these 24-week results, the selected dose of TMC114/RTV for treatment-experienced
patients in phase III trials is 600mg/100mg BID. TMC114 will be
studied in both treatment-experienced and -naïve patients in phase
III trials.
Tibotec
Inc., Janssen-Cilag and Tibotec Therapeutics are members of the
Johnson & Johnson family of companies.
For further information about Tibotec,
visit www.tibotec.com
Additional
TMC114 Articles
TMC114/Ritonavir
Shows Considerable Antiviral Activity in Patients with Extensive
Baseline PI Resistance and Is Active against Multi-PI-resistant
HIV
-
6/03/05
New
Anti-HIV Therapies from Existing and Novel Drug Classes
-
3/07/05
Effect
of TMC114, a Potent Next-Generation HIV Protease Inhibitor,
with Low-Dose Ritonavir on Atorvastatin Pharmacokinetics -
11/01/04
New
Protease Inhibitor (PI) TMC 114 Demonstrates Potent Activity
in Multiple PI-experienced Patients -
2/25/04
Second Generation Protease
Inhibitor TMC114 Is Extremely Potent against PI-resistant
HIV - 11/21/03
TMC
114, a New Protease Inhibitor - 7/25/03
New HIV Antiretrovirals
SPD 754 and TMC 114 -
7/18/03
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