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$300 hepatitis C combination to enter clinical trials
Keith Alcorn, 2016-04-13 22:00:00
The Drugs for Neglected Diseases Initiative (DNDI) is launching
clinical trials in Thailand and Malaysia to test a combination of sofosbuvir
and ravidasvir, an NS5A inhibitor, in at least 800 people with all genotypes of
hepatitis C virus (HCV). The combination, manufactured by Egyptian company Pharco, could be
made available for US$300 for a course of treatment if it proves safe and
effective, DNDI executive director Bernard Pécoul announced ahead of the 2016
International Liver Congress in Barcelona on Wednesday.
The studies aim to test an affordable pangenotypic
combination and to provide data for regulatory submission.
Affordable pangenotypic treatment for hepatitis C would
allow many lower- and middle-income countries to treat a wide range of people
with hepatitis C, without the need for genotyping, reducing the cost of treating
Ravidasvir has already been studied in patients with genotype
4 HCV infection in Egypt, where a
recently presented study showed that a combination of ravidasvir and
sofosbuvir cured between 86% and 100% of people treated, according to duration
of treatment and whether ribavirin was included in the regimen.
The studies in Malaysia and Thailand will test the
combination in comparison with sofosbuvir and daclatasvir, the only
currently recommended pangenotypic combination. The studies will test the
combination using a public health approach, where the only criterion determining
treatment will be cirrhosis status. Study participants who do not have cirrhosis will receive a
12-week course of treatment; people with cirrhosis will receive a 24-week course
of treatment. The study will recruit people with all genotypes of HCV;
genotypes 3 and 6 are particularly prevalent in both countries, “and we wanted
to test in countries with a large genotype range – and particularly 3 and 6
which are the most complex to treat,” Bernard Pécoul of DNDI told aidsmap.com.
The studies will examine efficacy, safety and
pharmacokinetics of the study drugs with a view to providing clinical as well
as manufacturing data for regulatory submission – including World Health Organization (WHO)
prequalification – of the ravidasvir/sofosbuvir combination manufactured by
The studies will also provide data on drug-drug interactions,
in particular with antiretroviral drugs for HIV treatment. The prevalence of
co-infection with HIV and hepatitis is high in Thailand and these data will also
be especially relevant in Brazil, Eastern Europe and southern Europe, where co-infection
Recruitment will begin in July 2016, and the 300-person
Malaysian study aims to complete recruitment within three months, indicating
that study results may become available during 2017. DNDI also hopes to study
the combination in populations in South Africa and Mozambique, where genotype 5
The study forms part of a five-year strategy for development
of affordable treatments for hepatitis C launched by DNDI. The cost of hepatitis C treatment is a major barrier to
curing people and eliminating hepatitis as a public health problem. The original sofosbuvir product Sovaldi, manufactured by Gilead Sciences, costs $27,921 in Spain and $53,010
in the United Kingdom (although prices paid might be considerably lower due to
negotiations regarding volume).
Voluntary licensing agreements between Gilead and Indian manufacturers have resulted in very large cost reductions. A recent analysis suggests that the cost of manufacturing a combination of sofosbuvir and daclatsavir in India might fall to under $200 if order volumes continue to grow, but purchase of the Indian generic versions of the drugs is restricted to named lower-income countries, and many middle-income countries are excluded from purchasing generic versions of each drug by the terms of voluntary licensing agreements.
Malaysia and Thailand are among the many middle-income
countries that are excluded from the voluntary licensing agreements that Gilead
and Bristol-Myers Squibb, the intellectual property holders of the hepatitis C
drugs sofosbuvir and daclatasvir, respectively, have concluded with generic
companies. Of the up to 150 million people infected with chronic hepatitis C
globally, approximately 75% live in middle-income countries.
Achieving widespread access to a combination at less than
$300 per course of treatment will require some governments to take decisions regarding
which tools they can use to reduce the price of sofosbuvir. For some countries
this will be taking advantage of voluntary licenses; for others it will be use
of the TRIPS-Plus provisions of international trade agreements, which allow
governments to oppose patent applications or to override patents and use
compulsory licenses on public health grounds.
The licensing status of ravidisvir means that it will be
widely available at an affordable price.
Ravidasvir was licensed to Pharco by Presidio, a US-based
biotechnology company, for manufacturing in Egypt. Presidio has licensed
ravidasvir separately to DNDI in a broad range of middle-income countries with
a higher burden of hepatitis C including India, Brazil, South Africa, Thailand,
Indonesia and South Korea, and DNDI also has an option to take up a license to
sell the drug in higher-income countries (Europe, North America, Australasia
and Japan) from March 2018. No patents cover lower-income countries in Africa
Ravidasvir is licensed to other companies in North Africa,
the Middle East, Russia and China.
Pharco chief executive officer Dr Sherine Helmy told a press
conference that he hopes that the price of the combination will fall by $50 a course
until it reaches $150 a course in 2020. He also hinted that Pharco may have
other affordable drugs in development that could be paired with ravidasvir to
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