BARCELONA, Spain — What started with a single patient with hepatitis C insisting that he would take generic direct-acting antiviral medication imported from China with or without the help of his doctor blossomed into a global clinical trial that is curing patients at a fraction of the cost of brand-name therapies.
In fact, interim results from the ongoing REDEMPTION-1 study show sustained viral response at 4 weeks with generic treatments for chronic hepatitis C virus. The findings, presented during a late-breaking session here at the International Liver Congress 2016, were met with resounding applause.
"Generic versions of sofosbuvir, ledipasvir, and daclatasvir are being mass produced for 1% of the current retail price in the United States," said lead investigator James Freeman, MD, from GP2U Telehealth in Hobart, Australia. But "in what must be one of the greatest tragedies of modern times, these lifesaving medications are not being deployed on a mass scale."
To date, 448 of the patients enrolled in REDEMPTION-1 have been treated with generic products. Generic sofosbuvir was used in combination with generic ledipasvir in 45.8% of the patients, with generic daclatasvir in 42.6%, with generic daclatasvir plus brand-name ribavirin in 6.0%, with generic ledipasvir plus brand-name ribavirin in 4.7%, and with brand-name ribavirin in 0.9%.
Most patients (63.9%) were infected with genotype 1 disease, but 27.5% were infected with genotype 3. Mean age was 54.4 years.
"This is quite a sick cohort of patients," Dr Freeman explained. Nearly 50% of the patients were treatment-experienced, and 31.3% had cirrhosis.
The interim analysis involved 236 of the patients who had completed a course of treatment. Overall, the percentage with viral titers at the lower limit of quantification was 99.6%. For sofosbuvir plus ledipasvir, it was 99.2%; for sofosbuvir plus ledipasvir, it was 100%; and for sofosbuvir plus daclatasvir, it was 100%.
Sustained viral response 4 weeks after treatment, available for 144 patients, was 94.4% overall, 93.7% for sofosbuvir plus ledipasvir, and 97.4% for sofosbuvir plus daclatasvir.
In terms of safety, "no new or unknown side effects were reported, with headache, fatigue, and insomnia being the most common," Dr Freeman reported.
Three patients with compensated cirrhosis temporarily decompensated on treatment initiation but were able to continue. All four deaths in the study cohort were related to hepatocellular carcinoma; one patient died before hepatitis C treatment began, two withdrew early in the course of treatment and entered palliative care, and one died before sustained viral response at 4 weeks could be assessed.
The interim REDEMPTION-1 results are similar to those seen in phase 3 trials of branded treatments, and should reassure clinicians about prescribing generics for hepatitis C, said Dr Freeman, whose father, John Freeman, MD, is founder of the FixHepC Buyers Club, which helps patients import their medications.
"As a doctor, writing a script for hepatitis C medications for a patient should be a no-brainer," he told Medscape Medical News. "Provided a doctor is happy that the supply chain is solid, what is the problem with giving someone generics? I'm not an advocate for pharmaceutical companies; I'm an advocate for patients, and my job is to make them feel better."
He said clinicians can take comfort in the story of HIV generics.
"In 2004, Médecins San Frontières sponsored a doctor in Cameroon to do a study on HIV generics," Dr Freeman explained, and they were proven effective. "Prior to that, half a million people were on HIV generics; it's now 15 million."
He pointed out that although he initially felt obliged to analyze the generic drugs that his patients imported, this is no longer an issue.
"When we were initially doing this, there were no generics on the market, so the raw active pharmaceutical ingredients were sourced, and that required testing. Since then, it's gone from 'home-cooked out in the back shed' (although with reasonably careful quality control) to industry-scale manufacturing," he said.
"A company like Cipla, which is based in India and makes Hepcvir-L — a generic version of Harvoni [a fixed-dose combination of sofosbuvir plus ledipasvir made by Gilead] — makes about 100 times as many antivirals as Gilead. They are massive; the scale is hard to fathom."
A separate study on the cost of generic and brand-name hepatitis C medications was presented at the meeting by senior REDEMPTION-1 investigator Andrew Hill, MD, from the University of Liverpool in the United Kingdom.
"The treatments are very cheap to produce, but are still unaffordable in many countries because of the high prices charged by pharmaceutical companies," he told Medscape Medical News. "People are being refused treatment in the United States and Europe because of high drug prices."
Table 1. Cost of 12 Weeks of Treatment
|Sofosbuvir plus ledipasvir||$94,500||$615|
Brand-name drugs are significantly cheaper in Europe than they are in the United States, but are still much higher than in India.
Table 2. Cost a 12-Week Course Sofosbuvir Around the World
But the target price for generic drugs could be even lower, Dr Hill explained.
Using per-kilogram export prices for active pharmaceutical ingredients and a price-estimation algorithm, his group calculated what the cost of a 12-week course of generic treatment could be in the United States: $86 for sofosbuvir, $102 for sofosbuvir plus daclatasvir, and $222 for sofosbuvir plus ledipasvir.
These estimates include a 40% mark-up for formulation, $0.35 per month for packaging, and a $50 profit margin, he pointed out.
"Understanding the viability of licensed and unlicensed generic direct-acting antivirals for hepatitis C is critically important, and this study is very interesting," said Channa Jayasekera, MD, from the California Pacific Medical Center in San Francisco.
Early in the era of direct-acting antivirals, Dr Jayasekera and his colleagues predicted that drug costs and poor global advocacy would be among the biggest barriers to expanded access (N Engl J Med. 2014;370:1869-1871). "Seldom in the history of medicine have such definitive, curative therapies been developed for a disease so widespread and consequential to human health. We believe that robust efforts toward equitable access to these advancements are imperative," they write.
In most countries, drug cost is one of the leading barriers to treatment for hepatitis C, Dr Jayasekera told Medscape Medical News. "Thankfully, there has been a relatively rapid adoption of licensed and unlicensed manufacture of generics."
"These two studies reinforce our faith in the effectiveness of these nonoriginator drugs and the likelihood of further lowering drug costs," he explained. "We now have highly effective, safe, and more affordable drugs for the treatment of hepatitis C."
"However, availability does not equate with accessibility. Translating availability of these generics to large-scale accessibility in both developing and developed countries — with an eventual goal of hepatitis C eradication — will require high-level political commitment and sustained civil society pressure," he pointed out.
Dr Freeman and Dr Jayasekera have disclosed no relevant financial relationships. Dr Hill reports receiving a grant from UNITAID, a nonprofit global health initiative.
International Liver Congress (ILC) 2016: Abstracts LB03 and SAT114. Presented April 16, 2016.
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Cite this: Slashing the Cost of Cure: Hep C Generics' First Data Shine - Medscape - Apr 18, 2016.