all-oral treatments for hep c

[robo229]

does anyone have any experience with the all-oral regimen (inform-1) trial.  side effect?  It sounds too good to be true.  why are they now adding SOC (interferon+ribavirin) to the mix?  

[willing]

FDA restrictions on combining two novel agents may explain why inform-1 was conducted in Australia and New-Zealand.

However the fact that NO trials combining R7128 with either telaprevir or boceprevir have been held or are being recruited anywhere in the world has nothing to do with regulatory control (and I suspect everything to do with market control). Hopefully such trials can start after BC/TV approval.

[Upbeat]

This the real reason
studies must be conducted outside the U.S. because of an FDA policy requiring HCV drug testing to include interferon-alfa

[willing]

yes , agreed that $$ plays a huge role in the unfolding N$3/N$4a and N$5b story - but it's not clear that as patients there's much to be done. The story is a prime example of shortcomings in our current  for-profit-only drug development model,

For about 5 years, in light of the success of multi-drug cocktails in fighting HIV, it's been clear  that combined attack on two viral non-structural proteins would have a powerful synergistic effect. Along the way various candidates for protease (NS3/4a) and polymerase (NS5b) agents have fallen fallen by the wayside (biln2061, nm283, r1626, etc.) Finally, after  many delays two NS3 targeted drugs (tv/bc)  are finishing Phase III and one NS5b (r7128) is in Phase IIb. The obvious thing is to do is to combine the two best in-class candidates, and like newleaf's post above I've been sifting through aasld abstracts for a couple of years waiting for this to happen.  Nada, though (unsurprisigly) the combos have been found very effective in vitro.

Why ? Because as luck would have it the three best-in class survivors ended owned up owned by three different drug cos. So  we have Roche working with a relatively untried NS3 in inform1 (how many trials have we seen for itmn-191?) and now Vertex working with its newly acquired polymerase inhibitor in  upcoming tests. Merck is still out in the cold, but presumably busy on its own ns5b story. Unfortunately, market domination, though great for the respective  Merck/Roche/Vertex stockholders is irrelevant to the many ifn-intolerant or non-responders who must wait until each drug is individually approved before being able to test the combination.

The wait isn't all that long , about mid 2013 according to David Nelson, but you have to wonder why a few more of those desperately in need of non or minimal ifn tx couldn't have been helped by say a boceprevit/r7128 trial in the interim.

[nygirl7]

If they could achieve this they could probably charge more than interferon for it - so I'm hoping that would not be the only reason they would not be providing non-IFN cures for HCV.

[Upbeat]

I believe Vertex is now doing a phase 2 trial with vx950 and vx222.  They will be recruiting soon.

[inteluck]

I think the fact that interferon is so expensive and profitable has made the FDA and drug companies reluctant to make safer and more effective (CHEAPER) alternatives available. It is nonsense that all oral treatments are "just an idea" sofar. We have proof of concept from INFORM-1, and several new STAT-C's which are far more effective then ribavarin- Achillions ACH625 comes to mind immdiately. We have all the drugs presently to build a safe effective alternative to SOC. From a purely scientific POV, we could, with aggressive and progressive trials, find the right combinations that could eliminate interferon in 5 years at most.  It is a question of money. When they figure out that many of us will not treat with SOC and are waiting for the STAT-c's I think we will find alternatives available sooner than we think.

[newleaf09]

Just looked the study up at http://www.hivandhepatitis.com/2009icr/easl/docs/042809_a.html.  Small study, only 57 patients, divided into 6 groups, so each group would only have 9 or 10, I guess.  Lots of arms, but in the high dose group with the combination, 25% went UD in the 14 day dosing period.  Incredible.  They are trying the individual drugs with SOC and don't say if they are going to pursue the non-SOC combo course.   I hope we can learn some more at the AASLD meeting coming up. Fascinating.

[newleaf09]

It's too early to think about Inform.  Phase 1 trials involve very small numbers of patients and if the drug seems safe enough they move to Phase 2 with more patients and try to fine-tune the appropriate dose for best effectiveness.  It's the Phase 3's that can involve over a thousand patients around the world.  There are literally years between phases and years after they've proved the drug in trials before they can get the drug approved for marketing.  It's wonderful to think of curing HCV without interferon, but it will be with us for quite a while more before there is another option.

I would be surprised if anyone on this forum was among the small numbers who took part in the Phase 1 of Inform.  

[robo229]

Thank you all for your insightful responses.  You are a terrific group.  I'm just navigating my way through this.  Your help is much appreciated.
robo

[WriteItDown]

These trials (combining a protease inhibitor and a polymerase inhibitor without peg and riba) are still in Phase I.  There have been no trials over a long-term, to see if SVR can be obtained, as far as I know.  So presumably, unless they run into some safety issue, they will keep on testing and see what happens.  You just gotta wait!

http://www.roche.com/investors/ir_update/inv-update-2009-04-27.htm

[nygirl7]

Robo

Here's the most uptodate info I could find on all the protease inhibitor type trials - I dont keep up much since I'm now SVR but I had time this afternoon at work to google.

http://www.natap.org/2009/HCV/100409_02.htm

[nygirl7]

Honestly that just means I don't know but was taking a wild guess by the way!

[nygirl7]

I would imagine while they were having success at lowering the viral load it was not eradicating the virus (which is the only realy goal).  

That would be the only thing that makes any sense to me since the goal was originally not to have to use interferon.