KUALA LUMPUR, Sept 19 – Voluntary licensing for Hepatitis C virus (HCV) medication is linked to increased access to treatment in low- and middle-income countries, new research has found.
The research published in The Lancet journal, which was funded by Unitaid and Doctors Without Borders (MSF), found that voluntary licences — which are an agreement between originator and generic manufacturers that allows the production and sale of patented drugs in certain countries, subject to licensing terms — could contribute annually to an additional 54 to 69 people receiving HCV treatment per 1,000 individuals diagnosed with the viral infection.
This increase was particularly notable when compared against baseline annual estimates of HCV treatment uptake that varied between two and 187 per 1,000 diagnosed in 35 low- and middle-income countries sampled, comprising 19 nations with non-exclusive voluntary licences of HCV medicines by Gilead and/ or Bristol-Myers Squibb (BMS), and 16 countries with no such agreement in the control group.
The Gilead licence covers sofosbuvir, ledipasvir, and velpatasvir, while the BMS licence is for daclatasvir; both licences issued since 2014 are non-exclusive, which allows multiple generic manufacturers to produce the highly effective direct-acting antiviral (DAA) compounds.
Malaysia was included in the control group without voluntary licensing, but data of HCV treatment access here was studied between 2004 and 2014, before the-then Barisan Nasional government approved compulsory licensing of sofosbuvir in 2017 that angered American pharmaceutical companies. A compulsory licence for pharmaceuticals is a process where a government allows someone else to produce generics of a drug without the original drug maker’s consent.
“Licences maximise access by allowing generic companies to bypass the time-consuming process of patent oppositions, simultaneously offering originator manufacturers a more effective business model to enter developing markets,” said the study published last July by Bryony Simmons, Dr Graham S. Cooke, and Marisa Miraldo from Imperial College London.
“This model provides a balance between intellectual property rights protection and public health concerns, and our findings suggest that it is a suitable strategy to improve access to HCV treatments in a range of countries.”Bryony Simmons, Graham S. Cooke & Marisa Miraldo, The Lancet
The research found that voluntary licences were associated with an increase in the annual number of people accessing HCV treatment of 69.3 per 1,000 diagnosed when adjusting only for country and year fixed effects, while this rise was 53.6 per 1,000 diagnosed after adjusting for country-level covariates.
“This evidence supports the expansion of licensing strategies to include more countries and more treatments.”
The effect of voluntary licensing increased over time and was largest in the second year after implementation, the study noted, as it attributed the rise in treatment access after the introduction of voluntary licences to a bigger supply of generics that promoted competitive prices.
“Countries included in licensing agreements can procure generic DAAs from licensees at more affordable prices.
“This is supported by data from the 2018 WHO (World Health Organization) access report that showed that a range of generic manufacturers have entered the market and prices of generic versions of DAAs have fallen steeply, with the steepest price cuts seen in those LMICs (low-income and middle-income countries) where several generic producers compete,” said the research.
The study sourced Polaris Observatory data on the total number of people infected with HCV, diagnosed with HCV, and treated for HCV, and constructed a longitudinal panel of low- and medium-income countries over a 13-year period from 2004 to 2016. Polaris Observatory provides epidemiological data, modeling tools, training and decision analytics on Hepatitis B and C. It also contributes to WHO estimates for HCV burden.
Countries were included if they were classified as low- and medium-income countries by the World Bank in 2014, and had available data on HCV outcomes. The 19 countries with Gilead and BMS voluntary licences sampled in the research included Indonesia, Philippines, India, Pakistan, Nigeria, Ethiopia, and Ghana among others.
Treatment uptake was calculated as the number of people treated for HCV in a given year per 1,000 living people ever diagnosed with HCV.
After Malaysia rejected Gilead’s voluntary licence offer for sofosbuvir and used a compulsory licence to obtain a generic version of the HCV drug, a March 2019 report said that about 1,500 patients have been treated with a combination treatment of sofosbuvir and daclatasvir since the medicines were provided in government hospitals in March 2018.
Deputy Health Minister Dr Lee Boon Chye was quoted saying that the compulsory licence allowed for a generic version of sofosbuvir priced at US$300 (RM1,225) for a 12-week course of treatment, down from US$11,000 (RM45,000).
He said local pharmaceutical company Pharmaniaga Bhd and Egyptian drug manufacturer Pharco Corp will jointly produce a new HCV drug in Malaysia, ravidasvir, that is used in combination with sofosbuvir, with the treatment expected to be available here by year-end or first quarter next year.
Non-profit Drugs for Neglected Diseases initiative (DNDi) said in April 2018 that a phase II/III trial for 301 people treated with the sofosbuvir/ravidasvir combination treatment by Pharco showed a 97 per cent cure rate. The trial was run in Malaysia and Thailand by DNDi and co-sponsored by Malaysia’s Health Ministry. Health director-general Dr Noor Hisham Abdullah is on DNDi’s board of directors.
The Pharmaceutical Research and Manufacturers of America, which represents the US’ pharmaceutical research companies, said in its Special 301 submission last February to the United States Trade Representative (USTR) that Malaysia should be designated a “priority foreign country” over its “unjustified” compulsory licence for sofosbuvir.
A US think tank also told CodeBlue that new medicines may only be sold here five years after their US launch if Malaysia continues breaching drug makers’ intellectual property rights. Malaysia is classified as an upper-middle income country by the World Bank.
Some 450,000 Malaysians are estimated to be infected with HCV. HCV infection can lead to liver cirrhosis, cancer, and death. About 400,000 people die from the blood-borne viral infection every year that affects over 71 million people worldwide.