Sofosbuvir/daclatasvir combination could be produced for $200 per hepatitis C cure

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Month-by-month tracking of the prices paid in India for the chemicals used to make hepatitis C direct-acting antivirals shows that it is now possible to make and sell a combination of drugs to cure hepatitis C for less than $200, Dr Andrew Hill of Liverpool University told the Second European HIV Hepatitis Co-infection Conference in London last week.

If those drugs were bought at list price in the United States they would cost approximately $147,000 for a 12-week course of treatment – $84,000 for sofosbuvir (Sovaldi), manufactured by Gilead Sciences, and $63,000 for daclatasvir (Daklinza), manufactured by Bristol-Myers Squibb.

Tracking of shipments of active pharmaceutical ingredients (API) by indiainfodrive.com, a reporting mechanism for importers and exporters, shows that the value of shipments of the APIs that are used to make sofosbuvir, the world’s most frequently-prescribed hepatitis C direct-acting antiviral, has fallen from around $8000 per kilogram in January 2015 to around $2000 per kg by September 2015.

Glossary

generic

In relation to medicines, a drug manufactured and sold without a brand name, in situations where the original manufacturer’s patent has expired or is not enforced. Generic drugs contain the same active ingredients as branded drugs, and have comparable strength, safety, efficacy and quality.

cost-effective

Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

antiviral

A drug that acts against a virus or viruses.

Active pharmaceutical ingredients are manufactured in India and China and shipped to other parts of the world for final manufacture of a drug. Indiainfodrive.com tracks shipments in and out of India for a wide range of commodities by analysing customs data, which must declare the weight and value of items passing through customs.

By crunching these data, Andrew Hill and colleagues were able to track changes in the value of shipments of the APIs used in the manufacture of sofosbuvir and of daclatasvir. Using these prices, they went on to calculate how much it would cost to manufacture a finished product, using methods of calculation already validated for the estimation of antiretroviral costs. In the case of sofosbuvir, they found that even assuming a 50% profit margin for the manufacturer to cover capital investment and return to shareholders, it would now be possible to sell a 12-week course of the drug for $178.

“The supplies in 2015 are sufficient to treat 150,000 people with sofosbuvir, for 12 weeks. Even at these quite low volumes the prices have fallen by 70% in one year, and there is no sign of a levelling off in prices,” Dr Hill told aidsmap.com by email. 

Indian manufacturers are already making generic versions of sofosbuvir under voluntary licensing agreements with Gilead Sciences, selling for around $483 for a 12-week course of treatment in India. In comparison a generic version of sofosbuvir – again, manufactured under voluntary license – is sold for $900 in Egypt. The branded product Sovaldi, manufactured by Gilead, costs $27,921 in Spain and $53,010 in the United Kingdom (although prices paid might be considerably lower due to negotiations regarding volume).

Daclatasvir would be even cheaper. The cost of its active ingredients have fallen from around $10,000 per kg in January 2015 to $2000 per kg in September, implying a generic cost of $22 for a 12-week course of treatment rather than the $63,000 list price currently charged in the United States. This low price may be achievable imminently, Hill believes, as a result of the licensing of daclatasvir to the Medicines Patent Pool for lower-income countries.

These costings suggest that it would be possible to market a pan-genotypic combination of sofosbuvir and daclatasvir for no more than $200. But many of the middle-income countries with a high burden of hepatitis C, such as China, Brazil, Ukraine and Latin America, will continue to be excluded by the terms of voluntary licensing agreements from obtaining Indian generics – unless they pursue compulsory licensing. Dr Hill reminded the conference that the South African government’s threat to use compulsory licensing had been critical in opening the way to lower antiretroviral drug prices in the early 2000s.

In the case of hepatitis C treatment, people could take matters into their own hands without waiting for governments. In Australia the FixhepC buyers club is working to assist individuals in buying generic drugs to treat hepatitis C, carrying out quality testing to ensure that they contain active pharmaceuticals, and importing the drugs for personal use. (The FixhepC website contains details of import regulations regarding medication for personal use for Australia, New Zealand, the United Kingdom and United States, as well as details of how people can purchase medication from generic manufacturers).

Hill also challenged the claim that current US pricing of Sovaldi and Harvoni makes the drugs cost-effective. He pointed out that at current prices, the use of the drugs is only cost-effective when set against a lifetime of medical costs, and calculations of cost-effectiveness ignore the propensity of drug prices to fall over time. Similarly, claims that treatment at current prices is cost saving are misleading, Hill argued, pointing to recent projections published in Annals of Internal Medicine. Jagpreet Chhatwal and colleagues found that treating all eligible patients with hepatitis C in the United States over the next five years would cost $65 billion, but would save only $16 billion in medical costs over the same period.

The current levels of pricing are only sustainable, Hill believes, for as long as Gilead lacks price competition in developed world markets and faces no serious threat of compulsory licensing in middle-income markets.

“It only takes one company to be brave and say 'we aren’t going to charge £30,000, we’re going to charge £10,000', and they will make a lot of money,” Dr Hill concluded, to prolonged applause.