TOPIC: GT3: High SVR rates with Daclatasvir

High SVR Rates With 12-24 Weeks of Daclatasvir Plus Sofosbuvir With or Without RBV in Patients With Genotype 3 HCV and Advanced Liver Disease

www.clinicaloptions.com/Hepatitis/Confer...s/206.aspx?lg=mobile

This site requires a username and password, but given I was not asked to agree to any terms and conditoons, or provide any validation of being a doctor, you can just simply register an account, or try the username james [at] fixhepc.com and password fixhepc. Alternatively you can just look at the attached PDF.

This study is significant in that the n=468 makes it the biggest Sof+Dac study to date.

It reinforces things we already know like F3 is easier to treat than F4, and 12 weeks seems ok without cirrhosis.

What is really interesting is the failure to demonstrate any value from Ribavirin with 24 week regimens. Now the addition of Riba was at the choice of the treating clinician so they might have only added to the sickest patients (introducing selection bias), however in all cases the 24 weeks Sof+Dac performed better than Sof+Dac+Riba.

On another note the mortality of these patients during treatment was 1.5% or 7/468 - yes the trail was heavily biased towards sick people but neither having Hep C or treating it is 100% safe.

Thanks for the info here...I'm still trying to decide if I want to add Riba to my treatment. As a 2a who relapsed after Sof/Riba, I've not found any trials or studies for my Genotype showing that adding Riba to a 24 week tx of Sof/Dac is or isn't beneficial. I did read and wondered about one study that showed adding Riba to a G3 tx regime was actually not as effective as skipping it. Hmmmm....

While on the surface you might think that more is more, as in:

1 + 1 = 2

With antibiotics we know that is not always the case.

Take penicillin. It is what is known as bactericidal - it punches holes in bacterial cells walls and the bacteria explode.

Take tetracycline. It is what is known as bacteriostatic - it does not kill it just arrests growth.

Now the problem is that for penicillin to work the bacterium needs to be active, so if you add tetracycline it actually works WORSE

1 + 1 = < 1

Here is some systematic research that talks to it:

www.ncbi.nlm.nih.gov/pubmed/24867991

The thing with this data is that the n was pretty large and in the 24 week groups there is not a single case where Sof+Dac+Riba out performed Sof+Dac alone.

Thank you James,
I have been considering whether to continue Dac/Sof regimen with or without Riba as I am about to finish 12wks of Dac/Sof and with Geno 3a
and no fibrosis etc I am fairly confident to stay at 12 weeks based on that latest data.
Nobody knows yet what the long term potential side effects, if any, of those DAAs are, so absolute minimum is my belief.
The only weakness in those outcomes as far as I am concerned is the male/female ration of the different arms. I do not know if that is relevant but I dont think it has been clarified if it is NOT relevant.

I'm wondering why they haven't tried predosing the Ribavirin for a couple weeks. When it was done on interferon studies it dropped the viral load.

P.

I came across a couple forum discussions suggesting that increasing the duration of treatment from 12 weeks to 16 or 24 may be beneficial for GT3 patients without cirrhosis. I'm on my last bottles of Dac/Sof (week 10). My data is the following:

GT3a, treatment experienced (interferon + riba), fibroscan - 7.5 (F2),

Pre-treatment (September 2015):
HCV RNA QUANTITATIVE: 2,487,537 IU/mL
ALT(SGPT): 64 U/L (1-53 U/L)
AST (SGOT): 32 U/L (1-50 U/L)
GAMMA GT: 47 U/L (10-54 U/L)

Week 3.5 during treatment (Jan 2016):
HCV RNA QUANTITATIVE: <15 IU/mL
ALT(SGPT): 31 U/L (1-53 U/L)
AST (SGOT): 18 U/L (1-50 U/L)
GAMMA GT: 27 U/L (10-54 U/L)

My doctor is taking it easy, so the next time she wants to see me is one month after the completion of my treatment. She said that there is no point of tests during the treatment other than the week 4 test.

My question is does it make sense to extent my treatment? If so what would be the recommended duration?

I purchased the meds from Mesochem and encapsulated them, back in October last year. However after several appeals the insurance company ended up approving the medication and I have been on the original Dac/Sof. However, I still have the 3 months’ supply from Mesochem in my fridge, so I can’t start taking them if it will increase my chance of getting cured.

Thank you in advance for the reply.

Cheers,
Cole

The longer you treat the higher the chances of SVR.

If you take GT1 treatment failures as a case in point with 12 weeks the SVR rate is 94%, but at 24 it is 99%.

Seeing you have the medication I would suggest the medication is better in you than in the bin.

The required doses are 400 mg of Sof and 66 mg of Dac (because it is the 2 HCl salt and you need that much to get 60 mg Dac)

Hi, I just today received my first course of generic 400mg Sofobuvir and Daclatasvir. The script and the label on the container say 60 mg not 66 mg is this going to be a problem? This is the first time I have heard this being stated. Also is it better to take the meds in the evening or the morning?

Hi Radtek,

No problem with your dose of 60mg, that is the correct dose of Daclatasvir. What Dr James was referring to was those who were weighing up their own from the powder, 66mg of powder gives you 60mg of active Daclatasvir. If your medication was already made up into pills or capsules it will contain the correct 60mg of active ingredient (made up of 66mg of the raw material)

When to dose each day is personal, some like myself prefer the morning and others the evening. Just do it at the same time each day. Here is a useful thread on how to change timing if you decide that your original timing doesn't work for you.

fixhepc.com/forum/patient-stories/326-ti...medication.html#3003

It is usual for the label to say 60 mg Daclatasvir. To get that 66 mg of Daclatasvir 2HCl is required. The use of the 2 HydoChloride salt relates to it being more soluble (and probably more stable) than the free base.

If it was compounded you could check with whoever did it. If it's box product they will have used 66 mg of the 2HCl.

Some people who compounded their own medication did make the mistake of only using 60 mg of the Daclatascvir 2 HCl although for normal weight people that won't make any difference. For people > 90 kg it might. We know from practical experience that 66 mg of Dac 2HCl is close to the toxic limit for people < 50 kg.

Hi Everybody,
I was just having a look on Fixhepc "Genotype specific treatments" fixhepc.com/getting-treated/genotype-spe...-hepc-treaments.html and noticed the following information:

Sofosbuvir + Ribavirin for Genotypes 2 and 3

Accordingly, the best treatment for genotypes 2 and 3 is a mixture of sofosbuvir and ribavirin. Sofosbuvir is taken in 400mg pills while ribavirin is taken in 1000mg pills on daily basis. This combination was found to produce the best cure rate for patients suffering from genotype 2 and 3 Hepatitis C.

I was under the impression that Sofosbuvir + Daclatasvir was a better option (less side-effects and higher SVRs). Is this Sofos+Riba information perhaps outdated?

Regards,
RHF