|
 
- 现金
- 811 元
- 精华
- 0
- 帖子
- 307
- 注册时间
- 2007-6-4
- 最后登录
- 2023-2-8
|
本帖最后由 bond007 于 2011-7-20 12:29 编辑
转自LIVER411以前的帖子，貌似对REP9AC有点不利啊。
国外乙肝论坛知情人士谈REP 9AC的严重问题：
Subject: Re: [HB] Rep 9Ac
Ok, this will be my last debbie downer report today from the AASLD
Poster 482: REP 9AC
This poster was presented on Saturday, and it sure attracted a large crowd,
since it was the ONLY presentation at the entire conference that discussed a
new experimental HBV treatment. THE ONLY ONE. As such, I'm very hesitant
about questioning its validity, but...
There are serious problems:
1. What is REP 9AC? It's impossible to tell, although that in itself is not
uncommon in new drug development, but at the very least the researchers
need
to describe the compound and give some idea of the mechanism of action,
especially if they are looking for investors. In the program book it's
called a DNA-based amphipathic polymer, which makes it sound like some kind
of soapy gene therapy. One of the biggest challenge in gene therapy is how
it can be delivered through cell membranes and get inside the nucleus of
the
cell, find the specific gene site and react with it. It's a very new and
difficult area of research, and there are only a few different known
effective approaches. It has the potential to be quite dangerous, as it can
trigger unwanted immune activation. The poster doesn't describe how this
compound achieves this at all. The drug is administered by "slow IV
infusion", so it's probably not using a viral vector. It's called a HBsAg
release inhibitor, but again, no description of how it inhibits that
action,
and it's apparently acting independently from the HBs antibody, which rises
and falls in no direct relation to HBsAg levels.
2. The study was initiated by a Canadian company, but conducted in
Bangladesh. I'm unfamiliar with the medical research infrastructure in
Bangladesh, but for this compound to go from a study in ducks directly into
humans, I can't help but be concerned about the safety and ethical issues
here. Someone asked the Canadians why they didn't first do the study using
woodchucks - another animal model that are closer to human than ducks, the
company guy said working with woodchucks was too difficult...HUMM
3. The conclusions they drawn were way more positive than what the data
justifies. If there is a study design I failed to understand it. A total of
ten people were enrolled in the trial, which is still ongoing. One person
was disqualified (no reason given), another did not show up to his/her
appointments regularly, which leaves 8 people. These 8 people were infused
with drug in all different doses (ranging from 100-1200mg), some on once
weekly, some daily, all on different treatment durations, one was stopped
once they lost the HBsAG, had a rebound, and put back on treatment, two
have
been on treatment for 35 weeks (one lost HBsAg and the other had no
response), three out of the ten lost both HBsAG and HBV DNA and are
currently off treatment, but 3 are on treatment with no drop in HBsAG, one
with just HBsAg loss but not HBV DNA. It's all over the place.
4. The administration of the drug was "well tolerated", but no other safety
data were given, or safety measures monitored other than ALT/AST. Large ALT
spikes were seen in those who lost HBsAg, but these were not reported as
adverse events (at least two people's ALT went up to over 400 IU). ALT
flares is one of the major side effects that can stop drug development, so
it's extra alarming that this is not addressed.
5. No patient demographics or HBV genotype were provided.
So all in all, I can't say one way or the other if this treatment has
potential or it's really dangerous. I wish there's better news.
Lei |
|
楼主: ainile
发表于 2011-7-18 16:26
