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Author Topic: Koronis Scientific Advisory Board Confirms KP-1461 Clinical Drug Activity  (Read 3643 times)

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Offline John2038

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Koronis Pharmaceuticals' Scientific Advisory Board Confirms KP-1461 Clinical Drug Activity, HIV Ablation

Seattle, WA (May 19, 2009) -  Koronis Pharmaceuticals, Inc., a biotechnology company focused on the development of antiviral therapeutics, today announced that its Scientific Advisory Board (SAB) completed a comprehensive review of the current in vitro and in vivo data for its lead HIV drug, KP-1461. The SAB concluded that recently completed in vitro serial passage studies corroborated the original published data, demonstrating that KP-1212, the active form of the oral prodrug KP-1461, ablated HIV in equivalent laboratory experiments. Additional studies are underway to assess ablation with greater sensitivity.

The SAB also reviewed statistical analyses of in vivo data from clinical trials of KP-1461. They concluded that KP-1461 demonstrated a statistically significant decrease in HIV RNA at the highest dose level as compared to placebo in the Phase 1b study. Decreases in HIV RNA were seen in some patients in Koronis' Phase 2a study, though the results were not statistically significant. Each clinical study met its primary endpoint of demonstrating that KP-1461 was generally safe and well tolerated.

"The current data confirms that the drug results in a substantial loss of HIV in tissue culture, demonstrates antiviral activity in HIV-positive patients and supports the continued development of KP-1461 and Viral Decay Acceleration™," stated James Mullins, Ph.D., Professor of Microbiology and Medicine at University of Washington and Koronis SAB Chair.

According to Dr. Mullins, "Koronis has shown that in a repeat of previous work KP-1461 reduces HIV titer to below detectable levels without noting the drug resistance that is seen with currently approved HIV drugs. This demonstration of the VDA mechanism, if confirmed by further clinical studies, will dramatically alter the treatment paradigm for HIV patients."

Koronis is in the process of completing formulation refinement and designing the next clinical studies of KP-1461.


Source

Surprising isn't it ?

Offline veritas

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Welcome Back John,

KP-1461 ---- very suprising. However, I don't think I'd be rushing  out to enroll in a clinical trial.

Whenever data has to be studied that long, a red flag goes up for me. Maybe it will work out.

v

Offline mousey

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I am delighted to receive this good news today! But time will tell whether its going to work out  :-[
:: Believe in a cure ::

Offline Inchlingblue

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I've always felt that "viral decay acceleration" made logical sense; hopefully it can be achieved, and without significant toxicity. This is exciting and promising news re: KP-1461.

I came across this nice brief description of VCA on the Koronis website:

Viral Decay Acceleration™™ -- a theory originally conceived by Nobel laureate Manfred Eigen. Eigen described the complex and dynamic nature of viruses as “quasispecies,” and introduced the idea that it may be possible to defeat a virus by exploiting its complex, rapidly mutating form.

Since this drug isn't necessary in order to suppress viral load (we've already got good drugs that can do that fairly quickly and efficiently), I wonder how it would work with viral reservoirs on someone who is undetectable? Presumably it would make the virus replicate uncontrollably until it has so many mutations that it isn't viable anymore. Not sure if that sounds good when you're talking about <50 copies slowly coming from reservoirs. If this drug somehow activated all the virus in the reservoirs that would be.......a possible cure?

Oh, well, as mousey said, time will tell.
« Last Edit: May 20, 2009, 04:00:15 PM by Inchlingblue »

Offline carpediem98

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Inchling,

I'm going to play debate club for a second... it doesn't seem that KP-1461's mode of action really has much to do with activation of latent reservoirs... in fact, it would seem that KP-1461's greatest success could only come in the absence of HAART.  If KP-1461 destroys the virus by making it mutate itself into oblivion during replication, it would seem to me that you then want to create circumstances whereby HIV could actually replicate - i.e., no HAART.  The great part about it would be, according to the principle behind it, it wouldn't replicate MORE, per se, but in the process of replication it would decay faster than a viral population normally would.

However, at the end of the day, the latent reservoir problem remains the problem.  They have discovered that the drug Zolinza (vorinostat, or SAHA), "wakes up" one latent reservoir - found in resting lymphocytes.  Researchers said that there appears to be one (or, probably, more than one) other reservoir.  So, rather than being a complement to the current HAART paradigm, it would seem to me like in principle at least, KP-1461 is a potential alternative, and we'd still need that activating agent.  Zolinza, for instance, only targets a portion of the resting infected cells, and it costs around $8000 a month.  But if Zolinza becomes cheaper, and we find the other reservoirs and the compounds that wake them up... then we can look at eradication via HAART+activating agents, or (potentially), KP-1461+activating agents, or (to refer to another thread), an anti-PS drug+(or -) activating agents. 

In ten years, we MIGHT be saying to our friends, "Yeah, I once had HIV, back in the days when it was almost identity-changing to get it..."  or sex ed teachers might be saying, "Make sure to practice safer sex, because unlike gonorrhea which you treat with one pill, HIV takes months and months to get rid of..."

On that note, I'm going to go enjoy the weather in New York, which is gorgeous.

Offline NYCguy

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Agreed that Kp-1461 most likely would need to be taken in the absence of Haart and I believe that's how the trials were done (but I'm too lazy to check now).  However, I was so psyched about the theory behind this one that it's initial failure was really upsetting.  And it's taken AGES to get any kind of follow-up data and testing.  I remain very skeptical that this can move beyond theory but would be wonderfully happy to be completely wrong!
11/9/06 = #$%^&!
sometime early Dec 2006:
CD4 530 20%/VL >250,000 (&*$$%!!)
started Reyataz300mg/Norvir/Truvada 12-27-06.
1/30/07 CD4 540 30%/VL <400
4/07 CD4 600+ 33%/VL <50
6/9/07 CD4 720 37%/VL <50
10/15/07 CD4 891 (!) %? VL <50
1/2010 CD4 599 (37%) VL<50 (drop due to acute HCV)
9/2010 - looks like HCV is gone for good! And I'm finally drinking again, thank GOD
2013 - considering a switch to Stribild. but I love my Kidneys (but I hate farting all the time!)...
June 2013 - switched to Stribild.  so far so good...

Offline Inchlingblue

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What I said above about the reservoirs and KP-1461 was more along the lines of "wishful thinking," This is a drug that stimulates HIV to replicate and to make more and more "mistakes" along the way so wouldn't it be nice if it is able to stimulate latent virus.

The fact is  that with existing HAART the virus can be completely stopped from replicating if a patient is adherent and doesn't develop resistance. Whatever residual viremia exists is coming from the reservoirs so I'm just not sure what the role of KP-1461 would be if it's proven to work and be safe. Would it be another drug in the HAART arsenal for those that have developed resistance to most everything else and for those that would prefer to try it if the safety profile is good and because there won't be any resistance worries with it and because it would only be one drug as opposed to a cocktail?

One of the bloggers on Poz.com named Paul had an entry about this drug back when the study was halted. It's an interesting read and also very interesting are two of the comments that follow the blog entry. One by someone named JF Vittoz who claims that a similar approach called "viral suicide" was attempted by a scientist named Claude Reiss who says that "he was bluntly barred from getting support for preclinical trials from the french National Agency for AIDS Research and said that he was told by people from the pharma industry that he « would not be allowed to ruin a $36 billion/year (AIDS) business », as this new therapy would likely achieve full viral clearance."

Two comments below that is a comment from Claude Reiss himself. It's actually very thoughtfully written and worth a look, he sounds like a legit scientist who knows what he's talking about. He goes into detail re: KP-1461 and ends by saying, "I believe there is only a technical problem which Koronis could rapidly settle."

LINK:

http://blogs.poz.com/paul/archives/2008/06/my-journey-with.html
« Last Edit: May 20, 2009, 07:56:51 PM by Inchlingblue »

Offline John2038

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what would interest me to know is what will be the impact of this drug in someone under treatment but failing it.

In others words, let says someone have develop the K103N mutation but remains on treatment (to exactly continue to select this mutation).

What will happen to this mutation ? Will it disappears and the treatment continue to work then (after the last K103N have mutate) ?

Many scenarios remains to test with this drugs.

Offline carpediem98

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Ah, I understand, Inch.  :) 

John2038, that actually sounds like it could be a really effective strategy, assuming they do find that this drug doesn't disappoint again!

Offline Inchlingblue

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Update on Koronis 1461

I came across this recent interview (6/3/2009) with Jeff Parkins, Vice President of Clinical Development and Regulatory at Koronis. It sounds like they need more money in order to continue development. Some of his statements regarding the lack of funding for innovative products are of some concern.

Can you talk about your HIV lead, KP-1461?

KP-1461 is in phase 2 clinical development and since 2005 the drug has been administered to 61 HIV-infected patients—37 in a placebo-controlled, dose-escalating, 14-day dosing, phase 1b trial (KP-1461-102), and 24 in an open-label, 124-day dosing, phase 2a trial (KP-1461-201).  In each study the drug was found to be generally safe and well tolerated.

Human studies have shown evidence of anti-viral drug activity.  Today, further tests are being designed to confirm efficacy and define an optimal drug dose and formulation to support a pivotal trial design leading to product registration.

How is KP-1461 different from other treatments on the market?

If approved, KP-1461 would be the first HIV drug to utilize a non-inhibitory mechanism to control viral replication.  By avoiding direct suppression of viral replication, a VDA agent such as KP-1461 is expected to be better tolerated and more durable therapeutic against HIV.

All existing approved drugs suppress viral replication by inhibiting a critical enzymatic process or blocking viral entry to uninfected T-lymphocytes.  Each of these approved drugs exerts selective pressure on the virus as a consequence of suppressing replication.  It is selective pressure that leads to drug resistance and it is suppression of a particular enzymatic process that provokes the adverse side effects that characterize antiretroviral therapy today.

What is the biggest challenge facing Koronis right now?

Koronis’ biggest challenge is attracting the financial resources necessary to develop a novel drug mechanism for a disease that people mistakenly believe to be a well served chronic condition based on existing and derivative products utilizing current inhibitory mechanisms.

Koronis believes—as does the Center for Disease Control—that the HIV epidemic is far from over.  However, funding for HIV drug development has ebbed as the financial community has come to believe that the existing group of approved products is sufficient to address this epidemic.

What do you think is the biggest challenge facing the biotech industry as a whole?

Koronis’ challenges are shared broadly by other companies in the biotech industry as economic conditions, regulatory considerations and attitudes toward risk combine to influence the allocation of financial resources to later-stage and derivative products.  If there are to be next-generation products for tomorrow’s healthcare needs, it is necessary for the industry to address the shortage of development stage financing.

What’s up next for Koronis?

As Koronis concludes the proof-of-concept for VDA in HIV, the next step is a development partnership to fund additional late-stage clinical development.  In addition, Koronis is seeking a development partner for the preclinical HCV program.


LINK:

http://www.biotechblog.com/2009/06/03/koronis-developing-a-new-treatment-for-hiv/
« Last Edit: July 07, 2009, 01:48:41 PM by Inchlingblue »

Offline brazilianman

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 >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:(blá, blá, blá, foundation bill gates. why they do not liberate the results of the tests? we want to see the numbers of the fall of the viral load and increase cd4 . email pra they asked when they go to liberate the numbers of the revision of the tests. who wants to make protest the same? >:( >:( >:( >:( >:( >:( >:( >:( >:( >:(

Offline brazilianman

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e-mail for koronis

I am decepiciondo with the koronis, I thought that she was a serious company, after the FDA ordering to suspend the tests of kp1461. I thought that we teriamos in fact the true numbers on the program. but what I see are only declaration of the president of the company in the media, we want the truth. of this skill the company passes to its shareholders and customers whom seriousness does not have. I repeat. which is the true numbers of the tests

Offline Inchlingblue

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I am decepiciondo with the koronis, I thought that she was a serious company, after the FDA ordering to suspend the tests of kp1461. I

Clinical Development
Phase 2a Trial
An open label Phase 2a trial of KP-1461 was designed to evaluate the safety, efficacy and tolerability of KP-1461 as a monotherapy in treatment-experienced HIV-infected patients.

This study enrolled 27 of the 32 patients targeted for the trial. Koronis stopped this trial prior to complete enrollment in order to conduct additional non-clinical studies, which have since demonstrated in vitro efficacy consistent with original non-clinical studies. The trial suspension was not requested or required by the FDA and was not related to any safety concerns or adverse events during the trial. KP-1461 was shown to be generally safe and well tolerated with mild to moderate drug-related adverse events

LINK:

http://www.koronispharma.com/KP1461forHIV.html

Offline brazilianman

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  >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:(    
where are the numbers? why not present? so speak to media. but not proved anything. a company lives of credibility. and that the Korona has not shown to the market and to customers. this is fact. I would be happy if it were true. but not for the life of dreams. they have to show the reports as every company does. why not show? again false? >:( >:( >:(>:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:( >:(

Offline mousey

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Doesn't looks promising now  :'(
:: Believe in a cure ::

 


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