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Author Topic: KP 1461  (Read 3287 times)

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Offline xxname

  • Member
  • Posts: 6
KP 1461
« on: October 14, 2012, 04:16:09 AM »
Any news about kp 1461?The site www.koronispharma.com  is outdated.
i'm  waiting for good news...........

Offline ichigo_kun

  • Member
  • Posts: 49
Re: KP 1461
« Reply #1 on: October 14, 2012, 12:41:04 PM »
Im hoping its still on progress, i dont know but of all the research going on this kp-1461s decay acceleration i like the most. Hope they find the right formulation for human test, although it really works on laboratory test

Offline Dr.Strangelove

  • Member
  • Posts: 206
Re: KP 1461
« Reply #2 on: October 14, 2012, 05:16:06 PM »
Don't want to crush any hopes but I have reason to believe that the KP 1461 thing was a scam.
When I find more time, I can write up why I think so.

Offline buginme2

  • Member
  • Posts: 2,834
Re: KP 1461
« Reply #3 on: October 15, 2012, 10:50:44 AM »
Don't want to crush any hopes but I have reason to believe that the KP 1461 thing was a scam.
When I find more time, I can write up why I think so.

I dont have any hopes to crush however, I am curious why you consider a particular companies research to be a "scam."  Seems like pretty strong words.  I can understand expecting a particular drug or method to not produce the desired result but scam?   Its not as if Kronis is pushing magic water.

Offline Skydrake

  • Member
  • Posts: 41
Re: KP 1461
« Reply #4 on: October 15, 2012, 01:02:34 PM »
Don't want to crush any hopes but I have reason to believe that the KP 1461 thing was a scam.
When I find more time, I can write up why I think so.

Something is smelling very bad:

http://forums.poz.com/index.php?topic=22133.0

Offline Dr.Strangelove

  • Member
  • Posts: 206
Re: KP 1461
« Reply #5 on: October 18, 2012, 04:16:24 AM »
Ah, thanks Skydrake, I wasn't aware of that thread, yet.

And there is also another thread here (as some of you are obviously aware).

Lets start with this comment from Tim:
After an in-depth conversation with some of the Koronis folks, I'm no closer to understanding how KP-1461 will somehow achieve either a sterilizing or or functional cure, nor am I understanding any of the potential clinical benefits of this agent. The public relations surround this drug appears much more solid than the science.

They have been very busy spreading the word about their new approach and although they have very little scientific data, they don't shy away from using the 'C-word ('cure', not 'cuntwaffle'  ;) ). Which reputable pharmaceutical company does that?
Have a look at their website:
http://www.koronispharma.com
They have three fancy 3D animations about their 'revolutionary new HIV therapy' but there is little solid information there.
Check out the Testimonials page. First of all, why would you have a testimonials page about a therapy that does not even exit??? Read the one comment that's on that page: "I have been reading about the new drug KP-1461 on your website...." apparently that's one random African woman what came across the Koronis website and is hoping for a breakthrough. Why would any pharma company put that on their website? My guess is they wanted a 'testimonials' page to look more credible.

Now check the actual page about KP-1461. Here, they explain how the drug is supposed to work. Scroll down you see the structural formula of KP-1461! Have you ever seen any pharma company post the structural formula of their drug in development on their website? I haven't. Anyone who's worked with a pharma company knows that they are extremely discreet about these kind of things; make people sign non-disclosure agreements and so on... So, this just doesn't add up.

Now for the science. As several people already pointed out in the other thread that I linked above, KP 1461 claims to be a path to a cure but the problem is that, while it may increase the mutation rate of the viral RNA, it does not affect the reservoirs. In the latent cells the viral genome (which unlike many other viruses is a single stranded RNA and therefore already has an intrinsic higher mutation rate) has been incorporated into the human genome of that cell (which is DNA). There is no way how KP 1461 can affect the viral DNA at this stage.
The thing is that we already have many drugs that successfully kill the free virus in the blood stream. Even if KP 1461 could kill the virions by accelerated mutation, the problem with the latency still exists. Several people have pointed that out in the thread I linked above but the Koronis guy avoids that question:
Unfortunately, I'm unable to respond to each individual post
Also, see Tim's quote above. Even in an in-depth conversation with Koronis, they could not explain how this could possibly be a cure.

And now for the scientific publications. They link to several papers on their website. These are already a few years old. They've been published in reputable journals such as PNAS. They are legit. But they are just the basic research. They propose a new approach that needs to be investigated further.
Needless to say that none of these peer-reviewed publications suggest this might be a pathway to a cure of HIV.
Check out the review "Lethal mutagenesis of HIV with mutagenic nucleoside analogs" on that page. Even this publication that Koronis links to on their website points out in the last chapter 'Perspectives':
Quote
Viral latency is a serious obstacle to conventional antiretroviral therapy and is likely to present similar barriers to clearance by lethal mutagenesis.
The authors suggests that this viral decay through mutagenesis approach, if it works out might help positive patients that are resistent to other retroviral meds. So, basically they say, if it works it will be just like a another drug against HIV.
These older publications about the basic science of increasing mutation rates by nucleotide-analogs where not done by Koronis itself but by universities. Koronis picked up this approach from there.
But Koronis has published, too: link  Or rather, they finded this study.
What's interesting is, that their study was published in the journal Plos One. Unlike pretty much every other peer reviewed journal out there Plos One has the policy to publish anything, no matter if the results are new, interesting or important for that field of science - as long as it's technically sound. (Here's NATURE mocking Plos One for that policy: "The beleaguered paper eventually found a home at PLoS ONE, a journal that publishes all “technically sound” papers, regardless of novelty.")
In practice, scientists first try to publish their research in reputable, high-impact journals first. When it gets rejected there because it is not interesting or important enough, they take it to Plos One. I'm not saying it is a crap journal but whenever you see a publication from that journal you should take it with a grain of salt and wonder 'why did they decide to publish it there?'. Especially so if it's "revolutionizing HIV therapy" as Koronis claims doing.
So what did the find in this short term study? From the abstract:
Quote
Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study.
Err what? Well, no wonder they didn't get this published in one of the reputable HIV journals.

As you see, nothing in the Koronis story adds up. I don't have a smoking gun to prove it's a scam but there are plenty of red flags everywhere.

Oh damn, I wish I had seen this earlier. There is even an article here on the blogs of POZ.com about the whole case: link
Quote
FDA had asked them to repeat a set of tests called, serial passage experiments where HIV is exposed to varying concentrations of a drug in order to force drug resistance to develop. This is a normal part of the drug development process. The FDA required Koronis to repeat their earlier serial passage experiment, because drug resistance did not emerge in the earlier experiments. The idea was to keep the experiment going until resistance did emerge.

It never emerged, because the experiments showed that the drug was having no affect whatsoever on HIV. They went and looked at the results from the US study, and found little to no evidence that the drug was working. Had the clinical data shown the drug working, it would have likely trumped the lab results.

Of course, I don't know what's really going on with that company. My guess is that  they picked up that lead with the nucleoside analogs which was developed at some university and looked promising at first. They were probably hoping to turn this into a new HIV drug. Halfway along the way, they realized that it's not working out the way they hoped. Despite of that they create a huge buzz to get some investors money to keep the whole thing going a little longer. And now might be the time where the whole thing is silently buried. I don't expect to hear (any breaking news) from them again. In fact, I would bet money on that.

What pissed me off is that they play with our hopes for a cure. They produce a few fancy 3D animations for their website that may impress a layman but have no substancial information, they do plenty of PR, they register a trademark for 'viral decay acceleration', they even create a Wikipedia article about 'viral decay acceleration', trying to give themselves some credibility, but they have little to no scientific data to back up any of their claims for 'Revolutionary HIV therapy' and 'cure'.

PS. Sorry for the long post.
« Last Edit: October 18, 2012, 04:53:03 AM by Dr.Strangelove »

Offline Skydrake

  • Member
  • Posts: 41
Re: KP 1461
« Reply #6 on: October 18, 2012, 11:34:12 AM »
PS. Sorry for the long post.

Absolutely not. It is exhaustive and very interesting. Anyway (not wanting to be polite as you), the short version still could be "KP-1461 is scam"

Offline buginme2

  • Member
  • Posts: 2,834
Re: KP 1461
« Reply #7 on: October 18, 2012, 03:43:30 PM »
So can we file this away in the same drawer as magic water?

I think you are dead on with the whole "cure talk" coming from a pharmaceutical.  You really need to have your ducks in a row before you start throwing around the c word.

Sangamo has also been throwing around the c word like crazy and to my knowledge they havent cured anyone.  Even if they "think" they may someday be on to somethi g seems pretty irresponsible to throwing around the word now. 


Offline Skydrake

  • Member
  • Posts: 41
Re: KP 1461
« Reply #8 on: October 18, 2012, 04:37:45 PM »
But Sangamo showed plenty of data, very detailed, for every step it did.
It shareholders would not forgive a behaviur like Koronis pharma.
 

Offline buginme2

  • Member
  • Posts: 2,834
Re: KP 1461
« Reply #9 on: October 18, 2012, 04:57:25 PM »
But Sangamo showed plenty of data, very detailed, for every step it did.
It shareholders would not forgive a behaviur like Koronis pharma.
 

Data for what?  Data for curing someone? Data for improving anyone's outcome? I think not.  Just because something looks promising?  If you are going to hold one company to a certain set of standards you really should hold them all to it.

Offline Skydrake

  • Member
  • Posts: 41
Re: KP 1461
« Reply #10 on: October 19, 2012, 04:23:24 AM »
Data for what?  Data for curing someone? Data for improving anyone's outcome? I think not.  Just because something looks promising?  If you are going to hold one company to a certain set of standards you really should hold them all to it.

Mainly data about the lowering of viral load in patients under several trials. Until now, no one was "cured" (eradicated), but only the eventuality to use ART every several years (hypothetically, never), it's a pretty improvement from the current situation.

Even in this forum there are reported several trials. Look at it.
http://forums.poz.com/index.php?topic=21770.0

Offline Nasty Weather

  • Member
  • Posts: 12
Re: KP 1461
« Reply #11 on: October 23, 2012, 08:58:43 PM »
I wrote to Koronis inquiring about KP1461, they replied with:


Thank you for your interest in Koronis Pharma. As you may know, Koronis'
drug-KP-1461-is based on an entirely novel drug mechanism - Viral Decay
Acceleration(tm) (VDA). The results of the Phase 2a "201" trial were
published in 2011 in PLoS One (see here:
http://www.koronispharma.com/news-2011-01-19.html).

This paper concludes
that KP-1461 causes a statistically significant increase in the number
of mutations that occur in the viral genome during viral replication. We
believe that the fitness of the virus is diminished by these extra
mutations and that a steady decrease in viral fitness will eventually
lead to decreased viral load.

 In three earlier in vitro studies we have
observed that the progressive accumulation of mutations in the viral
genome eventually extinguishes the viral population.

Koronis has designed a second Phase 2 trial and is seeking a significant
development partner in order to proceed with late-stage development of
the compound.

Additional funding would be necessary to support
initiation of Phase 3 trials. As you may be aware, today's approved
drugs have been shown to be very effective in suppressing viral
replication when patient compliance is high but that none of these drugs
has the potential for viral eradication.

 Moreover, these drugs cost a
great deal of money and require chronic/life-long administration;

leaving an unmet medical need associated with achieving a sustained
virologic response (SVR) and/or functional cure. We believe that VDA's
distinctive mechanism has the potential to introduce eradication and a
sustained virologic response as additional therapeutic outcomes.

If you have not viewed there is an interesting 4-minute long Adobe flash
presentation that introduces the drug mechanism and explains the
implications and can be viewed by clicking on this link (please make
sure your volume is on):
http://www.koronispharma.com/video/Koronis-6.swf . Additional videos can
be seen at www.koronispharma.com .

We are pleased to share this information with you and thank you for your
interest in Koronis.
 
 I dont think this is anything new

Offline Skydrake

  • Member
  • Posts: 41
Re: KP 1461
« Reply #12 on: October 29, 2012, 01:34:31 PM »
thanks Nasty Weather,
anyway, even with this answer, I still don't understand how to get rid of proviruses, the cells with viral genome already transcripted.
The future generations of viruses can have too many mutations to futher replications, but for reservoirs with the original viral DNA already inserted (before any mutation), the damage is done.

In order to understand the potential of this approach as functional-adjuvant therapy (even without eradication), it could be very interesting to have the opinon of  indipendent researches (or almost-indipendent, not employees of Koronis Pharma), so I'd like to have access to the full article of:

Safety, Tolerability, and Efficacy of KP-1461 as Monotherapy for 124 Days in Antiretroviral-Experienced, HIV Type 1-Infected Subjects.

It is a very recent study on KP-1461 as antiretroviral. The preview is available on NCBI :
http://www.ncbi.nlm.nih.gov/pubmed/22738014

Can someone have the access of the full article?
At least, to the conclusion.



« Last Edit: October 29, 2012, 01:37:17 PM by Skydrake »

 


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