Here’s my notes for the presentation and the presentation as a PDF and PPTx

HCVgenericsprojectpowerpoint-FINAL.pdf

HCVgenericsprojectpowerpoint-FINAL.pptx

And here I am giving the presentation with my eyes closed!

— Title
REDEMPTION-1 is an ongoing open label study assessing the safety and effectiveness of generic direct acting antiviral Hepatitis C medication. This is an interim analysis of the all results available to date.

— A Global Tragedy
Hepatitis C, Hepatitis B, HIV, TB and Malaria are the 5 major causes of infectious disease death worldwide.

In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market.

Across the world 150 million people are infected with Hep C and it causes over ½ a million deaths each year, but, in what must be one of the greatest tragedies of modern times, these life saving medications are not being deployed on a mass scale.

It is sobering to reflect that more patients died last year than received the new treatments.

— The Deployment Problem Is Price
The deployment problem is price.

Although the ingredients for a 12 week course of Sovaldi cost less than $100, the US retail price is a $84,000

To put that price in perspective if Apple put the same 100,000% markup on a new iPhone it would cost $1 million dollars.

— Background
So the staggering prices of these new medications prevent patient access to safe and highly effective treatment.

But… Generic versions are being mass produced for under 1% of the current US retail price, in countries where the patents have been rejected.

And… Under the laws of Australia, the UK, and many other countries, individuals have the right to import a three month supply of medication, for their personal use

— The Legal Basis Of Personal Importation
Patents provision monopoly rights that are open to abuse, however other laws provision other rights.

Article 60 of the World Trade Organization TRIPS agreement makes small consignments exempt, and in line with Article 60 most countries allow some form of personal medication importation.

The fixhepc website was set up to help patients safely access generic medication and the forum there has over 1000 patients discussing their generic treatment experiences in real time.

— Methods
When the first patient asked for help, stating he was going to import generics with or without me, I concluded I could improve his safety if the medications he sourced were shipped to me first for testing. The deal was if they passed testing he could take them, and if not they were going in the garbage. The medications tested correctly, the patient took them, and he’s now past SVR24 and cured.

That single patient might have been my only patient, but the news leaked and 1 became a dozen, who in turn became hundreds. Thus was born REDEMPTION.

Consecutive patients were enrolled and assessed pre-treatment, during treatment and then for SVR

The objective was to answer the two key clinical questions – do generics work? and are they safe?

— Sofosbuvir NMR
For interest here is an NMR spectrum of some generic sofosbuvir. NMR is one of a range of techniques, such as High Performance Liquid Chromatography, Mass Spectrometry and X-ray crystallography that can establish the precise nature and purity of a medication.

— Over 400 Patients Worldwide
Although REDEMPTION is based in Australia the gp2u Telemedicine platform allowed patients from around the world to enroll

— Baseline Characteristics
On the right you can see the genotype breakdown with the majority genotype 1, just under 1/3 genotype 3 with smaller percentages of the other genotypes.

448 patients enrolled.

There is a roughly 50:50 split between SOF+LDV and SOF+DCV with just over 10% also using ribavirin

This is a relatively unwell cohort with nearly 50% treatment experienced, over 30% cirrhotic, and a significant number who had previously been rejected from at least one clinical trial.

There was a slight male bias, an average age of 54 and a mean viral load of 2.8 million

— Viral Response
Let’s look at the on treatment viral kinetics The scatter plot dots are the viral load at various time points, and the size represents the log number of patients. Blue is Ledipasvir and Pink is Daclatasvir.

Unlike the usual reporting which stops at < LLOQ (<15) we have differentiated < LLOD as another data point and I think this makes evident a 2 stage kinetic decay – the first stage is rapid, but the second is substantially slower and it’s this slower second stage that dictates the minimum treatment duration. The 3 grey lines are from data published in the Lancet in 2014 about the on treatment kinetics for SOF+PEG+RBV. As you can see the response for both the generic combinations used was substantially faster than this demonstrating the impact of effective NS5A inhibition. The difference between the SOF+LDV and SOF+DCV kinetics, where Daclatasvir looks slower, is an artifact due to it’s higher use in GT3 where the kinetics are slower than in GT1. If we look only at GT1 with SOF+DCV we see the response is slightly better that SOF+DCV and it crosses