Any new treatments coming soon?

[Marlies52]

Are there any new less invasive treatments coming out say within the next 5 years?  I heard something about BILN 2061 and ISIS. I am type 1b genotype with alt 14 and ast 45 and the viral load is about 1 million, whatever that means.  I heard of all the sides of the TX and it scared me to death.

[AK - Hepper]

BILN has been sidelined due to toxicity in animal studies.(Saw this at Johns Hopkins site about a week ago) There is another protease inhibitor called Vertex being studied, you might try a google search on that. If you scroll down you can read about the new vaccine being tested in St. Louis, I haven't heard of ISIS til now.

[willing]

Hi Timbo - do you have a link for the biln toxicity results? I looked at Dr. Sulkowski's previous postings (under investigational therapies) but couldn't find anything. I'm pretty skeptical about biln but am surprised that it's toxic.

[Galen]

According to a press release from Boehringer Ingelheim Pharmaceuticals dated 10/29
http://us.boehringer-ingelheim.com/about/pressreleases/102803_hepatitis.html

  Press Release

Hepatitis C Drug Development at Boehringer Ingelheim

Ridgefield, CT, October 28, 2003 – The journal Nature has published an article describing a novel, small molecule anti-hepatitis C virus (HCV) compound discovered by Boehringer Ingelheim at its virology research center in Laval, Québec, Canada. The compound, named BILN 2061, is an orally active inhibitor of the HCV NS3 protease and the first member of this new drug class to be tested in humans. The Nature paper describes the discovery and early clinical trial results with BILN 2061 and demonstrates the promise of this class of anti-HCV agents for the treatment of HCV disease.

Administration of BILN 2061 to a limited number of patients infected with HCV for two days resulted in a marked reduction of the hepatitis C virus plasma levels and established the first proof-of-concept in man for an inhibitor acting by this mechanism. Routine chronic safety testing of high, supra-therapeutic doses in animals did, however, show relevant side effects which need further analysis. Boehringer Ingelheim is currently studying the available pre-clinical data in order to decide on their impact on the clinical development of this substance. There are currently no trials ongoing with BILN 2061 and decisions about future trials will be made after thorough evaluation of toxicity findings in animal studies

[layla]

I hope it's ok to throw a question in here. Before tx I had joint pain for about 7 years then after the second month on tx it completely went away. It was weird but great. Now I am having some joint pain again. Not as severe but non the less it's there in the elbows and knees. Could this mean the virus is doing this? I was undetectable at 6 months. I'm on 38 this week. I did test RA positive before tx but on the labs it was barely over the norm by only 1 point. I saw a RA doc and he said I definately didn't have it which I believe. Is there any info conecting this to actual virus being present? I'm worried about this but if there is I want to know. Anyone? LL

[AK - Hepper]

Thanks, Galen, I went digging but couldn't remember exactly where I read that,(sorry Will) but I did ask my doc about it last Wednesday and he confirmed it.
Layla, that could be caused by the riba, I know my shoulder got really painful about 3 weeks into tx and lasted for 3 or 4 months, gone now. Old boating injury, me and my brother were drinking and he drove me shoulder first into a tree OUCH!!!

[mikeymike2]

Bad news about BILN - I kind of built up my hopes about it.  Do people think this is the end of BILN, or can the problems be overcome?
Following a biopsy I've been advised by my doc that my liver is unlikely to suffer that much damage in the next fives years so I was going to delay treatment in the hope that new treatments come along - such as BILN.  I'm beginning to wonder if this is the right thing to do.  The $64,000 question I guess.

[MichaelT]

Here is a great summary:

http://www.frontiernet.net/~monty/hcvpipel.html

[Dirac]

I too had this kind of pain in my hand fingers before
treatment. I finished treatment 9/5 and started feeling
it again one month later. I had the same concerns that
you have now and my doctor told me not to worry. This
pain could be related to any thing else, we started to
have cold weather here in Boston for example and to make
me feel better he decided to measure my alt and ast.
The results came back 14, 15 which are even better
when I was in treatment. I wish that my experience
with this doubt could help you. I wish you the
best of luck.

[Tallblonde]

I'm facing the same $64,000 question.  I'm sure you're grateful, as I am, that there's little if any damage to the liver at this point.  But unlike people who have no choice but to immediately and agressively pursue treatment, we face a fork-in-the-road dilemma.  There's no guarantee that treating now will cure our disease (and it could even make it worse, not to mention the potential long-term impact of side effects), but there's also no gurarantee that better treatment models will be available to us in the future.  It's  potentially a "damned if you do, damned if you don't" scenario.  A crystal ball would come in handy right now, wouldn't it?

Susan

[newtex]

Your comments in (  ) about possibly making things worse brings up a question. I have been diagn. with cirrhosis from 20+ yrs. hep c! Is there concerns out there, that while tx is needed, it could be causing further liver damage....I am starting tx. in approx. 3 weeks. My doc wants to do 1 more baseline lab because my alt was so high,( 567 ). I'm not sure if I will be on Rebetron or Pegasys.

[Tallblonde]

I'm sorry if I caused you additional concern.  It's my understanding that some people don't respond to treatment and, in fact, their viral loads actually increase dramatically once treatment is started.  If I'm wrong about that, I'm sure someone here will correct me.  

My viral load is extremely low at this point and I don't have any significant fibrosis, so I don't want to risk pissing off the virus by picking a fight with it (by initiating treatment). On the other hand, I don't want to regret not taking this thing on when my chances of beating it are probably the best they'll ever be.  It's a catch-22 for me.

Best wishes to you.

Susan

[MajNeni]

I think there is some evidence that as long as your cirrhosis is mild and compensated (i.e. poor old liver is still doing its job), Pegasys may be your better choice, and may give better results.  I personally found the side effects more tolerable, having tried both...
Maj Neni

[willing]

that's the same press release that accompanied the <a href="http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v426/n6963/abs/nature02099_fs.html">publication </a>in Nature of the initial biln results. I just read it as the usual corporate "forward-looking statement" disclaimer regarding further development and testing (important here because of the huge interest) - not that Boehringer is abandoning development. Am I missing something ?

[AK - Hepper]

Hard to find a whole lot of info about this, here's what I came up with, seems to be the same thing Galen posted

contact  Boehringer Ingelheim Canada Ltd/Ltee Public Relations

Hepatitis C Drug Development at Boehringer Ingelheim
Ingelheim, Germany,
28 October 2003 - The journal Nature has published an article describing a novel, small molecule anti-hepatitis C virus (HCV) compound discovered by Boehringer Ingelheim at its virology research center in Laval, Québec, Canada. The compound, named BILN 2061, is an orally active inhibitor of the HCV NS3 protease and the first member of this new drug class to be tested in humans. The Nature paper describes the discovery and early clinical trial results with BILN 2061 and demonstrates the promise of this class of anti-HCV agents for the treatment of HCV disease.
Administration of BILN 2061 to a limited number of patients infected with HCV for two days resulted in a marked reduction of the hepatitis C virus plasma levels and established the first proof-of-concept in man for an inhibitor acting by this mechanism. Routine chronic safety testing of high, supra-therapeutic doses in animals did, however, show relevant side effects which need further analysis. Boehringer Ingelheim is currently studying the available pre-clinical data in order to decide on their impact on the clinical development of this substance. There are currently no trials ongoing with BILN 2061 and decisions about future trials will be made after thorough evaluation of toxicity findings in animal studies

[willing]

AK - thanks, I guess we'll have to wait and seee.

newtex: a recent, much-discussed, <a href="http://www.natap.org/2001/aasld2/day21.htm">study</a> found that, based on two biopsies 20 months apart, combo tx left patients  with more advanced fibrosis only 8% of the time. Selection of a more virulent strain by the meds has been <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10400744&dopt=Abstract">reported</a>  but, as far as I know, hasn't been quantified, and doesn't seem to affect therapy.

[TravisB]

I got this off an article about tha latest liver conference

Future Therapies
The current standard of care for the treatment of previously untreated hepatitis C infection is once-weekly pegylated interferon plus ribavirin. This therapeutic regimen has overall SVR rates of 52% to 54%, meaning that approximately 50% of patients do not respond to therapy. Because of these response rates, many new therapies are being evaluated for the treatment of patients with hepatitis C infection. Several in vitro studies with novel protease inhibitors and polymerase inhibitors were presented during this year's AASLD meeting.

Prabhu and colleagues[12] developed small interfering RNA sequences* to target specific regions of the envelope and nonstructural protein 3 and 5 areas of the hepatitis C genome. The molecules successfully inhibited translation of the hepatitis C core protein in genotype 1a infection. Abid and colleagues[13] evaluated the antiviral activity of a novel NS3 serine protease inhibitor* and found it to be a potent inhibitor of hepatitis C replication. Dagan and colleagues[14] reported that the hepatitis C polymerase inhibitor BC2125* was able to reduce hepatitis C replication in vitro. These studies all report promising in vitro data. However, additional investigation with all of these compounds must be performed before human testing can begin.

BILN-2061* is a serine protease inhibitor that has been used in patients with chronic hepatitis C infection. Reiser and colleagues[15] reported on the use of this inhibitor in patients without significant fibrosis. Three patients with HCV genotype 2 infection and 7 with genotype 3 infection were randomized to receive either 500 mg of this serine protease inhibitor or placebo over 2 days. Five of the 8 patients treated with inhibitor demonstrated antiviral activity, with a decrease in HCV-RNA viral load. All patients had viral levels that returned to baseline levels within 7 days of stopping therapy. However, these findings were not as dramatic as those reported during last year's meeting in patients with hepatitis C genotype 1 treated with this agent.[16] Lin and colleagues[17] reported on an in vitro study comparing the antiviral activity of the protease inhibitor VX-950* with BILN-2061. Their findings suggest that VX-950 may be a potent inhibitor of hepatitis C replication. Further studies with both of these protease inhibitors need to be performed to adequately assess their utility.

[TravisB]

Some interesting stuff from the same article.  This really stresses the need to treat at as early as possible. The jist of it is that a 20 year old is twice as likely to SVR than an older person when all other factors were similar.  By older I'm assuming they mean 30+.


Foster and colleagues[11] reported that age of initiation of therapy had a dramatic influence on the SVR rates in previously untreated patients infected with HCV genotype 1. Data from 2 large international studies were analyzed and included more than 700 patients. Using a model that included age, race, ALT level, HCV-RNA level, and body mass index, it was found that a 20-year-old was almost twice as likely to have a SVR when all other factors were similar. This analysis concludes that clinicians and patients should consider the influence of patient age in the decision-making process regarding when to initiate antiviral therapy.

These findings support treating patients at an earlier age, regardless of liver enzyme levels or liver biopsy findings. These data, do not, however, support withholding treatment in older patients. The decision to initiate antiviral therapy must be made after careful discussion between the physician, patient, and patient's family, and must include, at a minimum, factors such as HCV genotype, patient age, liver biopsy findings, current patient quality of life, concomitant medical conditions, and stage of life.

[BobK]

BLN 2061 should be considered as proof of concept only at this point in time.  The problems they had with their chimps will make it very unlikely that this drug will be persued in its present form for treatment of humans.

regards,
BobK

[layla]

Just a comment. I also read back when I was dx that the younger you were the better your SVR chances were and yes a 20 year old chances were better but a 40 year old were also much better than say a 60 year old. After 50 and older chances started slipping and contunued to with age. My hep doc said the same. This was considered highly in my decision to tx since I am 44 even thought my VL was low. LL

[DH Bill]

My opinion is that you have to consider the persons state of health. At 54 I'm in better shape than a lot of people half my age. My doc has told me that has a lot to do with my good response to treatment. I have read a study on Pegasys that says the SVR rates are higher with a low viral load. I posted it a few days ago I don't remember where.
My doc left the choice up to me about tx as little liver damage after having hcv for 36 yrs and a viral load of 315,000. I'm 1b.
After saying all this I decided to tx at 54 rather than 64. I'm amazed that I just did shot #16 last night it's going faster than I thought it would. Hey I'm almost half done. YES!

[layla]

I just got am email from a friend who has quite a few years on you and he "was" a 1b. He got his 6 month post tx labs back this week and he is still SVR. Like you he was pretty healthy to start and took very good care of himself on tx. And I bet your positive attitude helps. It always makes my day to hear of someone getting SVR! The snow you mentioned gave me beautiful picture in my mind this morning. (Not the shoveling lol) LL

[DH Bill]

Thanks for the info it always helps. This site sure helps the attitude. BTW the shoveling went pretty good, sleeping better has helped my energy level.

[willing]

Hi - do you have any details on the chimps? - would be interested to read what happened. Seems ironic that a "designed" drug, from a solved X-ray structure, had non-specific effects. On the other hand, the Nature editorial that accompanied the paper did say the NS3's substrate-binding channel was shallow and featureless - I wonder what else the biln ended up binding to. We really should have a "chimp memorial day" on this site...

[rjasper]

i seen what everone was posting in here about biln 2061 and have been watching this hopefully what i have been hearing is good news for everone cdc still reports that there is alot of hope for blin 2061 and i have looked at other sites and i have come across this hopefully this is good news here it is




  





      22 November 2003
















      

Hepatitis C drug development at Boehringer Ingelheim

  28  October 2003  

Ingelheim, Germany, 28 October 2003 – The journal Nature has published an article describing a novel, small molecule anti-hepatitis C virus (HCV) compound discovered by Boehringer Ingelheim at its virology research center in Laval, Québec, Canada. The compound, named BILN 2061, is an orally active inhibitor of the HCV NS3 protease and the first member of this new drug class to be tested in humans. The Nature paper describes the discovery and early clinical trial results with BILN 2061 and demonstrates the promise of this class of anti-HCV agents for the treatment of HCV disease.

Administration of BILN 2061 to a limited number of patients infected with HCV for two days resulted in a marked reduction of the hepatitis C virus plasma levels and established the first proof-of-concept in man for an inhibitor acting by this mechanism. Routine chronic safety testing of high, supra-therapeutic doses in animals did, however, show relevant side effects which need further analysis. Boehringer Ingelheim is currently studying the available pre-clinical data in order to decide on their impact on the clinical development of this substance.

Scientific results achieved so far are available to the medical community.


General Information About Hepatitis C
Hepatitis C virus infection is a serious cause of chronic liver disease with more than 170 million infected individuals worldwide. Current interferon (IFN)-based therapies are suboptimal especially in patients infected with HCV genotype 1 and are poorly tolerated, highlighting the unmet medical need for novel therapeutics. The HCV-encoded NS3 protease is an enzyme essential for viral replication and has been considered an attractive target for therapeutic intervention in infected patients.


Boehringer Ingelheim
The Boehringer Ingelheim Corporation is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 156 affiliates in 44 countries and a total of about 32,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2002, Boehringer Ingelheim posted net sales of 7.6 billion euro while spending about one fifth of net sales in its largest business segment Prescription Medicines on research and development.


Contact:
Boehringer Ingelheim GmbH
Corporate Division Communications
Judith von Gordon
55216 Ingelheim /Germany
Phone: ++49-6132 – 77 3582
Fax: ++49-6132 – 77 6601
E-mail  

  








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p.s i do not know if this is gonna help the one in connecticut but seeing its the same company hopefully it will i recived this on there site on nov 22 2003 here is the link if anyone knows any diffrent please contact me ty ill also post the link for you

  
http://www.boehringer-ingelheim.com/corporate/asp/news/ndetail.asp?ID=1314

  


  




  

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