Knock the beast down.
Kick it to death for 8 weeks.
Then keep kicking for another 4, just to make sure its doesn’t jump up and bite you in the ass.
If you get tired, kick with your other leg for a while.

That reminds me of a quote from a businessman here:

Q: Would you kick a man while he was down?

A: Only if he looked like getting back up again…..

Twinvir launched on the 27th August 2015, so there are patients past SVR4 but not SVR12. The first SVR12 results will appear in mid March.

My first patients started on it mid November. All were viral load zero within 4 weeks.

Prior to using it we tested Twinvir at the NATA accredited National Measurement Institute. If you search the certification documents for Sofosbuvir and Ledipasvir for the word Twinvir you will see that testing noted. You can find those certification reports here:

http://fixhepc.com/blog/item/16-testing-provisions-patient-safety.html

We did RVR testing on Twinvir during the period 20-28 November and observed excellent clinical effects with the worst 1 week viral load drop being 1,200,000 -> 636 (F3), the best being 2 million to undetected.

If you read the TGA submission here:

https://www.tga.gov.au/file/8444/download

You will find it stated that:

Ledipasvir is practically insoluble (<0.1 mg/mL) across the pH range of 3.0-7.5 and is slightly soluble below pH 2.3 (1.1 mg/mL). The partition coefficient (log P) for ledipasvir is 3.8 and the pKa1 is 4.0 and pKa2 is 5.0.

This is why you must have stomach acidity to absorb it – without that it won’t dissolve well. Once it is dissolved it’s not in a crystalline form and will be absorbed. The normal volume of the stomach fluid is 20 to 100 mL and the pH is acidic (1.5 to 3.5) so I’m actually quite surprised it is not without food (to increase the acidity) but as you will read in the auspar document it still gets absorbed in the presence of food.

If you read Gilead’s submission to the European Medicines Agency here:

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003850/WC500177996.pdf

On page 8 you will find Gilead stating:

Three crystalline forms are known and ledipasvir acetone solvate is the designated commercial form. The first step for finished product manufacture involves the dissolution of ledipasvir in ethanol followed by spray-drying and thus precise control of morphology and particle size is not considered important.

Ledipasvir acetone is what Twinvir uses.

On the topic of crystalline forms most people don’t know that Gilead tested crystalline Form-I Sofosbuvir but substituted Form-II in the commercial product. See page 12 here, and note that the AUC data in the commercial product is inferior to what was trailed…..

https://www.tga.gov.au/file/6066/download

We will be publishing generic SVR results at EASL if our abstract is accepted. The are no nasty surprises in it.

It’s a process.

Patients need doctors to be skeptical of any marketing BS. It protects us all.

While I know we are less marketing, and less BS, I do understand the need for caution.

When I spoke with Prof Gane last week he was, without a shadow of a doubt, one of the most switched on patient advocates I’ve ever talked to.

You guys are lucky to have him.

As the results flow in I expect the evidence will be allowed to speak for itself.

That’s worrying…….will make the next 12 weeks’ wait (post treatment) a bit more stressful

Hello Honker,

1b is the genotype of choice (if choice was an option).

Here are the overall stats for Sof/Led

Sofosbuvir Ledipasvir

NAIVE
default: svr: 97%, trials: ION-1 98% (142/145) ION-3 96% 96% (165/172) Aggregate 96.8% (307/317)
gt1a: default: svr: 97%, trials: ION-1 98% (142/145) ION-3 96% 96% (165/172) Aggregate 96.8% (307/317)
gt1b: default: svr: 99%, trials: ION-1 100% (67/67) ION-3 98% (43/44) Aggregate 99.1% (110/111)
F4
default: svr: 97%, trials: ION-1 97% (32/33)
w12: svr: 97%, trials: ION-1 97% (32/33)
w12riba: svr: 100%, trials: ION-1 100% (33/33)
w24: svr: 97%, trials: ION-1 97% (31/32)
w24riba: svr: 100%, trials: ION-1 100% (36/36)
FAIL
default: svr: 94%, trials: ION-3 94% (102/109)
w12: svr: 94%, trials: ION-3 94% (102/109)
w12riba: svr: 96%, trials: ION-3 96% (107/111)
w24: svr: 99%, trials: ION-3 99% (108/109)
w24riba: svr: 99%, trials: ION-3 99% (110/111)

These don’t show GT1 8 week results, but ION-3 does:

http://www.hepatitisc.uw.edu/page/treatment/clinical-trials/61

Now if you look at slide 5 you see 94% and probably go – ick!

But if you look at slide 6 you will see that of the 215 people in the 8 week arm only 2% (2/123) with viral load < 6 million failed versus 10% (9/92) who had higher viral loads. On slide 9 you will see that 18% had NS5A RAVs at baseline (of who the vast majority still got to SVR) Not shown in the slides are the SVR rates comparing 1a and 1b in ION-1 and ION-3 but the upshot of that was that 1b is a little more responsive than 1a With 1b, treatment naive, non cirrhotic, Viral load < 6 million 8 weeks Harvoni offers 98-99% cure rate. Treating past that point is probably a waste of time and money because by 8 weeks the chances are a patient is cured. The last 4 weeks might help somebody in that remaining 2%, but for most patients they don't need it. That said for ~ $500 USD I would take the full 12 weeks myself for peace of mind, but if finances are an issue and you're treatment naive, not cirrhotic and have a VL < 6 million 8 weeks is not a bad option for both GT1a and GT1b.

Hello Josie,

After the first of March it should be possible to prescribe it on the PBS for you.

You will need these tests to hand for a prescription to be made, so you should arrange anything missing now.

http://fixhepc.com/getting-treated/how-to-do-it/what-your-doctor-needs.html

Your local GP should be able to do it for you if they follow the instructions at: http://fixhepc.com/gp

If not we can do it via an online consult at https://gp2u.com.au/

Hi Josie…I live in Bendigo, Victoria. I am on a waiting list at the Bendigo Base Hospital and have been for 10 months and counting (I will notify them soon that they can take me off the list)! I chose to take my treatment into my own hands and went through the Buyers Club to have my meds imported from China. I am now on my last week of treatment (3 months all up). The virus was undetected at my four week blood test. I also have a very supportive GP. You will no doubt know that in March some of the HEP C drugs will be listed on the PBS…..but I’m sure there will be protocols etc. that patients will have to meet to be able to have access to the drugs. I arranged to see a specialist (paid for it myself) to get the right tests run (i.e. genotype, fibroscan, viral load) and then made contact with Dr Freeman. Given you have private health cover you should be able to be referred to a specialist with minimal cost to yourself rather than be on a waiting list.

I was diagnosed in February 2015 and to say it was a shock was an understatement (as I am sure it is for everyone when they are diagnosed). Please take the time to read some of the stories on the forum and you will find that the information you read will give you a lot of hope and take most of your fears away.