GS-5816 new pangenotype NS5A inhibitor in mighty DAA combo trial
Isiscat2011 said
Nov 27, 2014
Zilkster: This one looks pretty good for you, doesn't it? Gilead just bought a shortcut voucher for faster FDA approval. Maybe the voucher will be used on GS-5816 ??
November 25, 2014
Gilead's 8-Week Hep C Cure Is Good for Genotype 3, Not 1 or 2
Eight weeks of Gilead Sciences' Sovaldi and GS-5816, with or without ribavirin, cured high rates of people with genotype 3 of hepatitis C virus (HCV), but yielded unsatisfactory results among those with genotypes 1 and 2, MedPage Today reports. Researchers randomly divided 120 people with genotype 1, 103 people with genotype 2, and 102 people with genotype 3 into one of four groups: Everyone received Sovaldi, plus either 25 milligrams or 100 mg of the investigational NS5A inhibitor known as GS-5816, with or without ribavirin. They were all treated for eight weeks. Results were presented at the Annual Meeting of the American Association for the Study of Liver Diseases in Boston.
Among those with genotype 1, 83 percent of the participants who took 25 mg of GS-5816 plus ribavirin achieved a sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure), compared with 81 percent of those who took 100 mg with ribavirin. In the arms that did not receive ribavirin, 87 percent of those who took 25 mg of GS-5816 were cured, compared with 90 percent of those who took 100 mg.
Among those with genotype 2 who did not take ribavirin, a respective 77 percent and 88 percent of the low and high doses of GS-5816 were cured. As for the genotype 2s who did take ribavirin, 88 percent of both those on the high and the low dose of GS-5816 achieved an SVR12.
Among those with genotype 3 who did not take ribavirin, a respective 100 percent and 96 percent of those in the low- and high-dose arms were cured. (One person in the high-dose arm withdrew consent to be in the study, which is why that cure rate wasn't 100 percent.) As for the genotype 3s who did take ribavirin, 88 percent of those taking the low dose and 100 percent of those on the high dose were cured.
Adverse side effects among those with genotypes 1 and 2 were mostly mild to moderate. There were four serious adverse side effects.
The adverse side effects for those with genotype 3 were mostly mild. There were two grade 3 or 4 side effects.
Would Gilead risk to cannibalize it early or on purpose postpone GS5816 release until Ledi brings enough profit?
I feel quite comfortable in saying there is no f*****g way Gilead will pass on the opportunity to maximize profits by releasing Ledi asap and then take a second bite at the apple by releasing GS5816 when it is most advantageous to do so. Timing is everything but this is a fluid situation so no way to predict with certainty.
I would not put it past them to table a better drug but the better drug will potentially have even greater profitability. Gilead wouldn't want to postpone it by much because other pharma combos will be getting some play depending on price.
Gilead will have an >2 month jump on Abbvie regardless of cost because S/L will be released first. If S/L and Abbvie are priced comparably docs will still choose Gilead's S/L. The GS5816 will arrive in time to treat and RETREAT harder-to-treat populations. It doesn't get much better than that!
I'll keep my eyeballs peeled for clinical trials, Zilkster. Anybody as committed as you is bound to kick the dragon's butt. :)
Zlikster said
Aug 20, 2014
I somehow missed their results from Astral-2 (back in April?):
"Study GS-US-342-0102 , is an ongoing randomized Phase 2 clinical trial in which treatment-naïve, non-cirrhotic patients with genotypes 1-6 HCV infection received a 12-week course of SOF plus the pan-genotypic NS5A inhibitor GS-5816. Patients received SOF 400 mg and either GS-5816 25 mg (n=77) or GS-5816 100 mg (n=77). In this study, 94.8 percent (n=73/77) of patients receiving the 25 mg dose of GS-5816 and 96.1 percent (n=74/77) of patients receiving the 100 mg dose achieved SVR12."
Can't find full report with info on genotype classification on those 144 patients that participated in it, but i would gladly "sacrifice" myself for their Phase III Astral-3 (600 patients) study ;) Too bad they do not show hospital locations, tho i figured out UK ones have address. Sent few emails to em. Keeping fingers crossed.
I wonder will they actually have any time to market properly Ledipasvir, considering GS5816 might be approved as soon as late 2015/early 2016 and by the results, it's way more potent than Ledi or any other NS5A inhibitor. Would Gilead risk to cannibalize it early or on purpose postpone GS5816 release until Ledi brings enough profit? Then again there is poor, left in the cold, BMS. They still need their own proper NS5B inhibitor to go with Daclatasvir and J&J's Simeprevir yields better results than Asuneprevir as NS3 inhibitor. Now their future from grim (Ledipasvir on market soon) got even grimmer with Gilead's pangenotype killer GS5816...wonder whats Merck doing? Waiting for Gilead to market SOF/LED for 1.5k $ per pill? :D
Tig said
Aug 19, 2014
When they are all addressed, someone, somewhere, will find something they left out ...
Tig
Isiscat2011 said
Aug 19, 2014
mallani wrote:
It's even effective against the S282T RAV generated by Sovaldi.
Oh, the irony.
Didn't Gilead state that the Sovaldi created RAVs will disappear on their own in a very short period of time?
mallani said
Aug 18, 2014
Hi Zlikster,
GS-5816 seems promising. Gilead claim it is a second generation NS-5A blocker, and is pan-genotype and effective against all known antiprotease RAV's, all known NS-5A RAV's and the baseline Y93H and A30K RAV's for Geno 3. It's even effective against the S282T RAV generated by Sovaldi. Sounds too good to be true!
If the Trials back up those statements, Ledipasvir may have a very short life!! Find a Trial buddy.
Tig said
Aug 18, 2014
Hey Zlikster,
Gilead seems to agree with you! I'm sure you've seen this but it's worth posting the link for those that haven't. Let's hope this next gen attempt is the one!
Considering Ledipasvir and Daclatasvir results for GT3 were pretty mediocre, new gen of NS5A inhibitor GS-5816 showed great results in Phase II (Astral 2) study. Could this be THE combo Sofosbuvir+GS-5816 for all genotypes?
Phase III study for us GT3s soon to start, wish Gilead would provide precise locations, not just cities :( i would gladly apply anywhere...
Zilkster: This one looks pretty good for you, doesn't it? Gilead just bought a shortcut voucher for faster FDA approval. Maybe the voucher will be used on GS-5816 ??
November 25, 2014
Gilead's 8-Week Hep C Cure Is Good for Genotype 3, Not 1 or 2
Among those with genotype 1, 83 percent of the participants who took 25 mg of GS-5816 plus ribavirin achieved a sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure), compared with 81 percent of those who took 100 mg with ribavirin. In the arms that did not receive ribavirin, 87 percent of those who took 25 mg of GS-5816 were cured, compared with 90 percent of those who took 100 mg.
Among those with genotype 2 who did not take ribavirin, a respective 77 percent and 88 percent of the low and high doses of GS-5816 were cured. As for the genotype 2s who did take ribavirin, 88 percent of both those on the high and the low dose of GS-5816 achieved an SVR12.
Among those with genotype 3 who did not take ribavirin, a respective 100 percent and 96 percent of those in the low- and high-dose arms were cured. (One person in the high-dose arm withdrew consent to be in the study, which is why that cure rate wasn't 100 percent.) As for the genotype 3s who did take ribavirin, 88 percent of those taking the low dose and 100 percent of those on the high dose were cured.
Adverse side effects among those with genotypes 1 and 2 were mostly mild to moderate. There were four serious adverse side effects.
The adverse side effects for those with genotype 3 were mostly mild. There were two grade 3 or 4 side effects.
http://www.hepmag.com/articles/eight_weeks_2501_26497.shtml
http://www.npr.org/blogs/health/2014/11/19/365254707/gilead-buys-shortcut-for-fda-drug-review-for-125-million
I feel quite comfortable in saying there is no f*****g way Gilead will pass on the opportunity to maximize profits by releasing Ledi asap and then take a second bite at the apple by releasing GS5816 when it is most advantageous to do so. Timing is everything but this is a fluid situation so no way to predict with certainty.
I would not put it past them to table a better drug but the better drug will potentially have even greater profitability. Gilead wouldn't want to postpone it by much because other pharma combos will be getting some play depending on price.
Gilead will have an >2 month jump on Abbvie regardless of cost because S/L will be released first. If S/L and Abbvie are priced comparably docs will still choose Gilead's S/L. The GS5816 will arrive in time to treat and RETREAT harder-to-treat populations. It doesn't get much better than that!
I'll keep my eyeballs peeled for clinical trials, Zilkster. Anybody as committed as you is bound to kick the dragon's butt. :)
I somehow missed their results from Astral-2 (back in April?):
"Study GS-US-342-0102 , is an ongoing randomized Phase 2 clinical trial in which treatment-naïve, non-cirrhotic patients with genotypes 1-6 HCV infection received a 12-week course of SOF plus the pan-genotypic NS5A inhibitor GS-5816. Patients received SOF 400 mg and either GS-5816 25 mg (n=77) or GS-5816 100 mg (n=77). In this study, 94.8 percent (n=73/77) of patients receiving the 25 mg dose of GS-5816 and 96.1 percent (n=74/77) of patients receiving the 100 mg dose achieved SVR12."
Can't find full report with info on genotype classification on those 144 patients that participated in it, but i would gladly "sacrifice" myself for their Phase III Astral-3 (600 patients) study ;) Too bad they do not show hospital locations, tho i figured out UK ones have address. Sent few emails to em. Keeping fingers crossed.
I wonder will they actually have any time to market properly Ledipasvir, considering GS5816 might be approved as soon as late 2015/early 2016 and by the results, it's way more potent than Ledi or any other NS5A inhibitor. Would Gilead risk to cannibalize it early or on purpose postpone GS5816 release until Ledi brings enough profit?
Then again there is poor, left in the cold, BMS. They still need their own proper NS5B inhibitor to go with Daclatasvir and J&J's Simeprevir yields better results than Asuneprevir as NS3 inhibitor. Now their future from grim (Ledipasvir on market soon) got even grimmer with Gilead's pangenotype killer GS5816...wonder whats Merck doing? Waiting for Gilead to market SOF/LED for 1.5k $ per pill? :D
When they are all addressed, someone, somewhere, will find something they left out
...
Tig
Oh, the irony.
Didn't Gilead state that the Sovaldi created RAVs will disappear on their own in a very short period of time?
Hi Zlikster,
GS-5816 seems promising. Gilead claim it is a second generation NS-5A blocker, and is pan-genotype and effective against all known antiprotease RAV's, all known NS-5A RAV's and the baseline Y93H and A30K RAV's for Geno 3. It's even effective against the S282T RAV generated by Sovaldi. Sounds too good to be true!
If the Trials back up those statements, Ledipasvir may have a very short life!! Find a Trial buddy.
Hey Zlikster,
Gilead seems to agree with you! I'm sure you've seen this but it's worth posting the link for those that haven't. Let's hope this next gen attempt is the one!
http://www.gilead.com/news/press-releases/2014/4/gilead-announces-phase-2-results-for-two-investigational-alloral-sofosbuvirbased-regimens-for-the-treatment-of-chronic-hepatitis-c
Tig
Considering Ledipasvir and Daclatasvir results for GT3 were pretty mediocre, new gen of NS5A inhibitor GS-5816 showed great results in Phase II (Astral 2) study. Could this be THE combo Sofosbuvir+GS-5816 for all genotypes?
Phase III study for us GT3s soon to start, wish Gilead would provide precise locations, not just cities :( i would gladly apply anywhere...
http://clinicaltrials.gov/ct2/show/NCT02201953