TOPIC:

Abbvie's new pangenotypic Glecaprevir/Pibrentasvir NS3/4a + NS5a combination has been awarded breakthrough designation based on results of phase 2 trials with GT1 patients who had previously failed DAA treatment. They will apparently also be presenting pangenotype phase 3 trial results at AASLD in Nov.

news.abbvie.com/news/abbvies-investigati...rapy-designation.htm

www.hcplive.com/medical-news/abbvie-gets...pic-hepatitis-c-drug

Probably still a way off but so far looks promising for relapsers in the future.

Glecaprevir pibrentasvir will probably get FDA approval soon. news.abbvie.com/news/abbvie-submits-new-...onic-hepatitis-c.htm
Abbvie filed for FDA approval, days after Gilead. The timeframe is about 8 months.
This combination is even more potent than sof/vel/vox for retreatment, has a different resistance profile.
That said, sof/vel/vox does have 97% SVR for retreating many cases.
The more different drugs for retreatment - the better. Some failed combinations require retreatment with drugs having a different mechanism of action and resistance profile. And if one doesn't work, it may be good to try chances with another one (although, there's debate if one should wait for a year before retreatment, especially when one has a s282t rav).

I wonder who will be the first one to copycat it. The retreatment market is about 18 million people - and there are no good options on the market currently.

Hi Vitrus,

Thanks for posting. It's reassuring to see that they have submitted the application for approval. When it is approved it will no doubt provide another option for retreatment that will be particularly useful for 'difficult to treat' patients. Ideally this and other new and more effective meds will also be available for treatment naive patients too, which will reduce the numbers who need retreatment. And that will be a great news!

However, while retreatment can be problematic for some of us currently I would also suggest that there are some good options already available in the currently approved/available medications depending on the patients genotype and/or other issues such as cirrhosis, etc.

99% SVR in Japanese CERTAIN-1 trial (January 2017) of glecaprevir/pibrentasvir.
(Gen 1 only, 8 weeks, 106 people).
The 1 remaining percent is one patient lost to follow-up.
www.businesswire.com/news/home/201701090...es-Achieved-Genotype

In previous November trials, SVR12 in 97.5% people across all genotypes.
news.abbvie.com/news/eight-weeks-treatme...onic-hepatitis-c.htm

While these results are encouraging it's worth noting that most Japanese are GT 1b which, along with GT 2, is the easiest GT to clear.

Gilead's 97% SVR for GT1 with Harvoni in 300 or so treatment naive low fibrosis patients in ION was shown to be 91.3-92% in a VA study of 4200+ real world veterans. The slightly higher result being in the with Ribavirin group.

What's good about these new drugs is that they are the most potent NS3/4 and NS5A inhibitors to date. Looking at GT3 we see this:




So ABT-530 needs 2 pM for EC50 whereas Daclatasvir needs 530 pM. That 265 x increase in potency is enough to deal with RAVs that confer 10x and 100x resistance (but not 1000x resistance). Similarly ABT-493 is 4x more potent than GS-9857 (Voxilaprevir).

To me the most exciting thing is that ABT-493 + ABT-530 + Sofosbuvir looks an awful lot like the mythical Perfectovir. Best in class inhibition at 3 different target sites.

One of the depressing things about ~90% cure is the sure knowledge that 10% will fail. Retreat and get 90% cure and overall we are at 99% but that missing 1% is still 1 real persons hopes and dreams per 100. These new agents offer real hope for cure for almost everyone.

FDA grants priority review designation to glecaprver/pibrentasvir.
It means it may get registered in the US late June.
Canada and the EU also recently granted it expedited review for approval.

news.abbvie.com/news/us-fda-grants-prior...-genotypes-gt1-6.htm

Are these two drugs going to be produced in Bangladesh?

I'm aware of at least one of the Bangladesh Pharma companies looking at it now, so probably yes. After Sof/Vel/Vox the next logical candidate for a generic is ABT-493/ABT-530