questions for agm, page-8

pesa,

You ask "Given the demonstrated effectiveness of Gileads new oral HCV drug without the requirement for interferon and ribavarin, where does the board see BIT225's place in the market, presuming its further trials are successful?"

You question domonstrates some confusion that seems to have been propagated here in relation to exactly what trials Gilead conducted and exactly what results they yielded. I suggest that from my reading, the trial results announced at the conference and touted here as a "cure" and not necessarily "without the requirement for interferon and ribavarin" at all.

In fact Gilead announced a number of HCV trial results at the conference and these need to be looked at separately as they involved different combinations of drugs in both dual and triple therapies. The combinations that I am aware of include:

1.a) sofosbuvir + daclatasvir
2.a) Sofosbuvir + ribavirin
2.b) Sofosbuvir + GS-5885 + ribavirin

Trial 1 which included the Bristol-Myers Squibb's NS5A inhibitor called daclatasvir. This combination "demonstrated high sustained response rates, and the addition of ribavirin did not add to its efficacy". Despite a cure rate of about 93% Gilead has announced that they "would no longer pursue studies of the sofosbuvir/daclatasvir combination" so this dual therapy will not go any further irrespective of how promising it looks.

Trial two contained both dual and triple combination therapies, both of which contained ribavirin. The combination of Sofosbuvir + ribavirin produced good results against genotypes 2 and 3 but not against 1 as the relapse rate is massive. On the other hand the triple therapy of Sofosbuvir + GS-5885 + ribavirin performed well against genetype 1.

You will note that the only good results that don't involve ribavirin were obtained using a drug not owned by Gilead and which Gilead has stated that it doesn't intend to progress trials with. All other sofobuvir combinations included ribavirin. In other words although it can be inferred that GS-5885 reduces relapse specifically in relation to Genetype 1, it has never been tested without ribavirin and results are week 4 after the end of therapy. While week 4 is considered significant from a dual therapy perspective, it is yet to be determined if the effects of GS-5885 in the tripple therapy hold true beyond that. One hopes so and the future trial sort of depends on this being the case but we won't know for a little while if that is true.

Despite comments made herein there is no interferon and ribavarin free dual therapy and there is no sucessful dual therapy for genetype 1 at all.

The above said there is no doubt Gilead is onto something with sofosbuvir to achieve rapid virological response which is one pieceof the puzzle. GS-5885 also seems to help prevent relapse in genetype 1 patients. But none of these have been proven to work without ribavirin. Nothing is yet known about relapse after the 12 week mark etc. In future trials Gilead will attempt to test a dual sofobuvir + GS-5885 therapy but it appears that the confusion over the various trials infer that this is what the cure rates touted in this recent conference relate to. In fact such trials have not yet even begun.


"Gilead said it treated study patients with two experimental drugs, sofosbuvir (formerly known as GS-7977) and another experimental medicine, GS-5885, plus the older therapy ribavirin. The group of patients showing 100% cure rates in the study were those with genotype 1 chronic hepatitis C who have not been treated in the past."


One if left wondering if given the success of daclatasvir in recent trial results Bristol-Myers Squibb will just roll over and play dead. I would reasonably think that they are looking at how their drug could be used in another combo like so many others. Admittedly the issues of rolling daclatasvir into a single oral pill might be an impediment but this shouldn't be a show stopper.