& T-1249: a new class of drugs
At ICAAC, Jay Laleazri
reported preliminary information on safety and antiviral activity when T-20 was
used in combination therapy for a small group of individuals with extensive
treatment experience. T-20 is a fusion inhibitor that is administered twice
daily by subcutaneous injection.
It is a new class of
drugs and itís not expected to have cross-resistance with currently available
classes. So it is expected to be of help to individuals with resistance to
currently available drugs. There is a concern about drug availability at launch
because this type of drug has never been manufactured before. In this study
people with extensive experience with prior treatment received a regimen
including T-20. Participants had received T-20 during previous short-term
monotherapy studies and patients were off T-20 for a median of 4 months
(range 2-8). One-third of patients were on drug holiday when screened for
71 participants were
enrolled to receive 50 mg T-20 BID by self-administered subcutaneous injections
in combination with drugs selected on the basis of genotypic resistance testing.
Nine patients had not yet reached 16 weeks; there were 7 discontinuations: 2
deaths due to progression to AIDS, none discontinued due to T-20 related
complications. This is primarily a safety study to look secondarily at antiviral
activity. Prior to receiving T-20 in this study (n=55) patients had used a
median of 11 prior drugs and 93% had used drugs from all 3 classes. In this
study patients received on average 4 drugs in addition to T-20.
Median baseline VL was
80,000 copies/ml and CD4s of 70. The study participants had been heavily
pre-treated. Percentage of patients with genotypic mutations associated with
NRTIs was 82%, 60% for NNRTIs, and 93% for protease inhibitors. 100% had PI
experience. 93% had experience with NNRTIs,, NRTIs, and protease inhibitors. In
this latter group, 55% had mutations at baseline with an average of 13
At 16 weeks, 60% (33/55) had VL reductions >1 log and/or <400
copies/ml, 36% (20/55) had <400 copies/ml, and 20% had < 50 copies/ml
using on-treatment analysis. The ITT analysis was about the same. Individuals
with triple class exposure and documented triple class resistance also had
similar results. Although the data was not shown Lelazari said there was no
difference in outcome between those who took drug holidays and those who did
At week 16, a -1.2 log
reduction in viral load was seen in the as-treated, triple class exposure and
triple resistance arms. Lalezari suggests this reveals the effect of T-20.
Additionally, he showed a slide suggested the viral load reductions of T-20 were
independent of baseline viral load and the number of drugs in a personís
regimen in the study. Lalezari concluded T-20 can be an effective antiviral drug
in HIV treatment.
Because T-20 was used in this study as part of a multi-drug combination
it may be difficult to characterize its effect but in previous short-term
studies the antiviral activity of T-20 has been seen, (1.0-1.5 Log).
Results. 7 patients had stopped
therapy. No withdrawals to date have been due to adverse events considered
related to T-20. 15% had grade 3 events possibly related to T-20 but no one
person experienced more than 1 event so Lalezari said he didnít feel there was
a trend showing association. There were 5 serious adverse events (7%) possibly
related to T-20 but Lalezari did not feel there was reason to believe they were
associated with T-20: elevated SGPT, elevated amylase, nausea & vomiting,
neutropenia, anemia. 67% of patients reported mild transient injection site
reactions. Lalezari concluded T-20 is safe and well tolerated as a twice-a-day
injection for 16 weeks in combination therapy.
16-week data on T-20 from the on-going Phase II clinical trial (known as study
T20-205) at Lisbon. The clincal data was previously reported at ICAAC. New
information was reported that T-20 antibodies in 55 patients who received 50
mg/twice daily by subcutaneous injections with combination therapy regimens did
not impact the serum levels of T-20 peptide after 16-weeks of therapy.
In addition, it was
recently reported that Trimeris recently entered into an agreement with
Mallinckrodt to augment Roche's manufacturing capabilities and supply large
quantities of T-20 peptide for clinical trials. This may help alleviate concerns
about drug availability for launch and expanded access.