Fresh hep C hope

Chemistry World ^ | 21 April 2010 | Sarah Houlton

[neverdem]

A new kind of compound to treat hepatitis C is showing promise in early clinical trials. The treatment, being developed by Bristol-Myers Squibb (BMS), was found to be very effective at lowering viral load, both in a Phase I trial published this week in Nature, and in early results of a Phase IIa trial presented at the European Association for the Study of the Liver's annual meeting in Vienna last week.

Current HCV therapy is not ideal. The standard treatment is with an interferon and the antiviral agent ribavirin, but is only effective in around half of all patients and is plagued with side-effects. Various new antiviral agents are under development, including protease inhibitors and polymerase inhibitors, and BMS-790052 works against a new target, the NS5A protein.

'If we are to replace interferon with small molecules, we would need at least two if not three, so we set out to look for new inhibitors,' explains Nick Meanwell of BMS's research team. 'We ran a chemical genetics screen, and found a single interesting inhibitor whose resistance mapped to the NS5A protein. We don't know what this protein actually does - it's very enigmatic! We took that lead compound, and after some very interesting chemistry we finessed out the pharmacophore, and that led to the final molecule which is now in clinical trials.'

BMS-790052 could offer a new treatment option for hepatitis C

© Nature

The hepatitis C virus has many different genotypes. The initial screen was run on type 1b, and BMS chemists got to work to find an analogue that was active more broadly. 'We had to understand how to inhibit type 1a, which was quite a challenge, but we solved it,' says Meanwell. 'Typically, there is an effect on viral load by the 12 hour point, and at the highest dose we are reducing viral load in plasma by almost 99.99 per cent.'

The compound also seems to be effective against other genotypes. The next step, says Meanwell, is a combination study where it will be given alongside the company's protease inhibitor BMS-650032, but without the standard interferon and ribavirin, which was given to patients in the reported trials. 'It's a small study and very early days, but we hope to release results towards the end of the year,' he says.

'It looks a most interesting compound,' says Geoff Dusheiko of the centre for hepatology at University College London, UK. 'Other groups have worked on NS5A inhibitors that have not shown the same level of potency, which is crucial. It looks like it has fairly broad activity across HCV genotypes, which would also be an important breakthrough.'

 

References

M Gao et al, Nature, 2010, DOI: 10.1038/nature08960

Also of interest

New hep C breakthrough

09 December 2009

A new microRNA-based hepatitis C treatment that could avoid drug resistance is being tested on humans after encouraging trials in chimps

Testing times: predicting hep C response

20 August 2009

A new genetic test could predict which patients will benefit from treatment, and which will suffer side effects

GSK snaps up hepatitis drug developer

31 October 2008

GSK is back on the acquisition trail with the purchase of hepatitis therapy experts Genelabs

[neverdem]

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect

Found 4 studies with search of: BMS-790052 | Open Studies for HCV

[neverdem]

That second link is for clinical trials recruiting patients if anyone knows folks with HCV.

[tang-soo]

My father was cured of Hep C during the clinical trials nearly 20 years ago. He had a heart attack at age 51 and is believed to have contracted HEP C during the treatment for that attack. When he started the treatment, a daily injection of interferon, he was told that only a third responded with positive results and it was an all-or-nothing scenario - ie there was no partial benefit. the treatment was to last a year and after 6 months they would perform an evaluation to see if he would respond and hence continue for the second half. After 6 months he was told there was no improvement and that he was not a candidate for the second half of treatment. Disappointed, he returned for his last blood test as part of the study. The virus WAS GONE! Hallelujah!

A week later, I heard Peter Jennings announce on ABC news that the treatment had passed trials and the FDA had approved the treatment.

Now 74 he is still doing well though he has other health issues and his body never fully recovered from the devastating side effects from the treatment.

[Prospero]

My brother was infected through transfusion following a near fatal motorcycle accident in 1984. We lost him last year, after a long battle. The treatments and clinical trials were not useful and debilitating in his case, though none of us are complaining after getting an additional quarter century of his company. Glad to see progress for others, as he would have been.

[pandoraou812]

Sorry about your brother. I have hep c & tried the treatments which made me sick & did nothing for me. I was told in 82 I had non A non B hep. I’ve been living with it ever since. I don’t know if I would even bother trying another treatment. I was told there is no cure for hep c yet I see people claiming they’re cured. I thought it went into remission.

[Eska]

I've had the Big "C" since my army days in 70's. Went through treatment in early 90's, no workey. Went through Pegatron/rebatol, around 2006, now that was some bad feeling stuff; only time I ever thought about putting a hole in my head, I mean seriously thinking about it. They said I was cured, but I figure it just slowed her down some.

I'm not tired or achey sick or anything and I've had it for 35 years or more. Figure I've got my moneys worth living in Alaska anyway. I'll probably drop over from heart attack like all my relatives in mid 60's;;;; so I got 7 more years;;; life is good. Every day is another lucky one.

[pandoraou812]

I got mine from a blood transfusion in my teens. I am always tired. I had a liver biopsy a few yrs ago. To my doctors shock & my surprise it came out really good. A few days later I came down with MRSA. I must have picked it up in the hospital. That darn MRSA has hit me a few times now & the antibiotics are liver killers. I doubt my liver is in very good shape at this point. I suppose I ought to go see my gastro dr before my health insurance changes... My gastro dr told me that if I tried the new treatment I would still be tired & frankly didn't see the point of me going through the side effects. I just take my milk thistle & some other things & pray all the time. At 52 yrs old I have a 10 yr old daughter & just want to see her grow up. My parents lived into their 80’s but all my siblings are dead. You are right, every day is a good one. Prayers for both of us & all people with hep c.