Industry Trend Analysis - Agreement Strengthens Pharco As An HCV Regimen Supplier - APR 2018

BMI View: Pharco Pharmaceuticals is strengthening its position as a supplier of hepatitis C drugs for the developing world and this agreement sees it broaden its reach from the Middle East and Asia into Latin America. From an intellectual property aspect, the key element of this agreement will be sofosbuvir, and specifically how Gilead responds. The company will be aware of the danger this agreement presents that Malaysia's compulsory licensing move will broaden into new territories, but the company has so far employed a relatively gentle touch regarding access to affordable sofosbuvir.

Egyptian pharmaceutical company, Pharco Pharmaceuticals, has entered into a new collaboration to provide an affordable hepatitis C (HCV) treatment regimen in Latin America. Under the terms of the collaboration, announced at the 18th International Congress on Infectious Diseases (ICID) in Buenos Aires, Argentina, Pharco will supply the active pharmaceutical ingredients sofosbuvir and ravidasvir. Pharmaceutical company Insud Pharma and Argentinian R&D company, Laboratorio Elea Phoenix, will register, manufacture and distribute ravidasvir and sofosbuvir in Latin America, whilst the Drugs for Neglected Diseases initiative (DNDi) will collaborate with trial data and jointly with non-profit foundation, Mundo Sano, will collaborate on advocacy activities to boost access to easy diagnosis and affordable treatment for HCV.

According to the DNDi, currently, a 12-week course of HCV treatment is available in Argentina for at least USD7,000, whilst in Chile it is available for USD12,000, and in Brazil for over USD6,000. Although the cost of manufacturing ravidasvir is potentially higher than some direct-acting antivirals (DAAs), the commitment from all partners to what the DNDi has termed a reasonable profit margin means that the target price of the new ravidasvir+sofosbuvir combination will be under USD500 in Latin America.

Agreement Complements MPP Initiative

Pharco's agreement with the DNDi complements an earlier agreement the Egyptian firm signed with the Medicines Patent Pool (MPP) in 2017. Under that agreement, the MPP entered into a licence and technology transfer agreement with Pharco for ravidasvir, noting that the DAA has the potential of working across all six major HCV genotypes. The agreement would enable the competitive supply of ravidasvir in low- and middle-income countries (LMICs), including high prevalence nations such as Russia, Ukraine, Egypt and Iran.

The MPP agreement expanded the geographic scope of a licence signed by Presidio Pharmaceuticals, the original developer of ravidasvir, and the DNDi in March 2016, extending coverage to several LMICs that were not included in the DNDi licence. In August 2014, Pharco licensed the drug in Egypt from Presidio.

Ravidasvir is an NS5A inhibitor that, in a Phase III trial in Egypt conducted by Pharco, demonstrated cure rates of up to 100% in patients with genotype 4 when used in combination with other treatments. The MPP-Pharco licence for ravidasvir is royalty-bearing over net sales in the licensed territory (4% in low-income nations and 7% for middle-income countries). Pharco waived royalties for paediatric formulations.

Under the March 2016 agreement, the DNDi and Pharco signed agreements covering the clinical testing and scale-up of an HCV treatment regimen for a price of just under USD300. At the time, the DNDi was sponsoring trials in Malaysia and Thailand of ravidasvir in combination with sofosbuvir with the objective of providing a pan-genotypic and affordable treatment for eventual distribution in developing countries. In a Phase III trial in Egypt conducted by Pharco and involving 300 patients, results showed that combining ravidasvir 200mg and sofosbuvir 400mg once daily for 12 weeks resulted in SVR12 rates of 98% overall (255/261 patients). For non-cirrhotic patients, the per-protocol results were 100% SVR12 (163/163 patients).

Malaysia Adopted Aggressive Patent Approach

The DNDi noted that countries in Latin America are adopting different strategies to face the high price of HCV treatment. However, a number of patent applications that could prevent affordable access to sofosbuvir are pending in Argentina and in other Latin American countries, all of which are middle-income countries (MICs) under the World Bank's classification.

These countries may take the lead of Malaysia, also an MIC, which, in September 2017, issued a 'government use' licence enabling access to more affordable versions of HCV treatments. This landmark decision will help the more than 400,000 people living with HCV in Malaysia access sofosbuvir, and could have repercussions in the global effort to provide affordable HCV treatments.

Commenting at the time, the decision to issue the licence was made after the Malaysian Ministry of Health's efforts to be included in the Medicines Patent Pool (MPP) and price negotiations with Gilead, the patent holder, were unsuccessful. The Government claimed that through the implementation of the Rights of Government, the cost of treatment would be lower and more patients could be treated. At the same time, access to treatment could be improved to achieve the Sustainable Development Goals target set by the UN and targets of the World Health Organization's Global Health Sector Strategy on Viral Hepatitis 2016-2021 to eliminate viral hepatitis as a major public health threat by 2030.

The procurement of the 400mg sofosbuvir tablets would be in accordance with the current government procurement procedures. The implementation of the Rights of Government for the drug would be for use in government facilities only, and would initially only be offered at 12 Ministry of Health hospitals. The selection criteria of patients that receive the treatment would follow clinical guidelines set by clinical specialists.

Subsequently, in November 2017, Malaysia-based Pharmaniaga signed a collaboration with Pharco and the DNDi to manufacture and supply a new HCV treatment regimen to be sold for USD300 in the public sector in Malaysia. The DNDi noted that, in partnership with the Malaysian Ministry of Health, it was running trials testing Pharco's ravidasvir with sofosbuvir. The clinical trial is ongoing in six hospitals and is co-sponsored by the Malaysian Ministry of Health, with initial results expected in 2018.

The agreement covers the manufacture and supply of ravidasvir, once approved in Malaysia, and a supply of sofosbuvir. The government use licence enables the importation of generic sofosbuvir in order to make the drug available in the public health system throughout Malaysia at affordable prices. The DNDi noted that a full 12 week course of treatment was available in Malaysia for around USD70,000.

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World Health Organization (WHO)/ BMI