Ravidasvir boosts hepatitis C elimination

Malaysia is the first country in the world to approve ravidasvir as treatment for chronic hepatitis C virus (HCV) infection. The availability of ravidasvir is significant in eliminating hepatitis C in Malaysia by 2030, in line with WHO’s global elimination targets.

An oral nonstructural protein 5A (NS5A) inhibitor ravidasvir hydrochloride (Ravida^®) was given conditional registration by the Drug Control Authority (DCA) Malaysia in early June 2021. This approval requires the product registration holder, Pharmaniaga Berhad, to submit additional and up-to-date data on the product to ensure its safety and efficacy remain current and the benefit outweighs the risk. [https://kpkesihatan.com/2021/06/04/kenyataan-akhbar-kpk-4-jun-2021-kelulusan-pendaftaran-secara-bersyarat-ravidasvir-200mg-tablet-bagi-rawatan-hepatitis-c/. Accessed on 16 June 2021.]

In 2016, the Ministry of Health Malaysia (MOH) in collaboration with the Drugs for Neglected Diseases initiative (DNDi) started working on improving treatment access and affordability for patients with hepatitis C in Malaysia. The primary outcome of this collaboration is the STORM-C-1* clinical trial, which is the pivotal trial for the product registration application and conducted at six centres in Malaysia and four centres in Thailand.

The two-stage, open-label, phase 2/3 single-arm clinical trial STORM-C-1 reported that of the 300 diverse patients included in the full analysis, 291 (97 percent; 95 percent confidence interval 94–99) patients on the combination of ravidasvir and sofosbuvir, a direct-acting antiviral (DAA), had sustained virological response at 12 weeks (SVR12) after treatment (95 percent confidence interval 94–99). [Lancet Gastroenterol Hepatol 2021;6:448–458]

Notably, 96 percent of patients with cirrhosis had SVR12 while no difference was seen in SVR12 rates among patients with HIV coinfection or previous interferon treatment. The treatment did not cause deaths or treatment discontinuations due to serious adverse events. Study authors said the treatment is potentially an “affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.”

Ravidasvir is the first treatment for HCV that has been developed through South-South collaboration involving MOH, DNDi, Egyptian pharmaceutical company Pharco, Pharmaniaga Berhad, and Médecins Sans Frontières (MSF). “The development of this new drug is the result of a partnership between public and private [sectors] sharing the same public health objective from the very start: the development of an affordable medicine,” said Dr Bernard Pécoul, executive director of DNDi.

Ravidasvir was developed and owned by Presidio Pharmaceuticals and licensed to Pharco Pharmaceuticals and DNDi for clinical development and commercialization. Pharco and DNDi partnered with Pharmaniaga for the registration and supply of ravidasvir in Malaysia and Southeast Asia. Ravidasvir and sofosbuvir costs US$300–US$500 for a 12-week treatment course and is available for free at MOH clinics and hospitals. The treatment is also available at selected GP clinics.

“Our goal is now to help foster the political will and financing needed for wide-scale roll-out of lifesaving testing and treatment for hepatitis C globally. The Malaysian example is a showcase of what can be done with the right will, the right partners, and the right tools,” said Pécoul.

The estimated prevalence of hepatitis C in Malaysia is about 400,000. MOH implemented the test and treat strategy at its health clinics and hospitals throughout the nation to find patients with HCV by using rapid test kits and treat them with affordable, safe, and effective combination treatment. [https://www3.moh.gov.my/moh/resources/Penerbitan/CPG/Gastroenterology/QR_Management_of_Chronic_Hepatitis_C_in_Adults.pdf. Accessed on 17 June 2021.]

“Although hepatitis can be cured, there is a vicious circle that stands in the way of providing treatment to all in need: the disease is mostly a ‘silent killer,’ the diagnostic process is complex, … and DAAs are often too expensive,” said Tan Sri Dato’ Seri Dr Noor Hisham Abdullah, Director-General of Health, MOH.

“Malaysia decided to act to break this vicious circle. We are actively screening to find ‘missing’ patients, rolling out [rapid test kits], and ensuring we have access to the best prices for treatments, including by conducting clinical research to identify additional affordable treatment options,” he added.

He said the journey towards elimination of hepatitis C began in 2015 with multiple series of engagements with companies involving medicines patents, price negotiation and to be included as one of the low- and middle-income countries (LMIC) for voluntary licence of medicines. Unfortunately, Malaysia neither qualified as LMIC nor afforded the costly medicines. However, the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) helped the government to exercise compulsory licensing by declaring hepatitis C is a public health concern in 2016. In 2017, voluntary licensing was offered to the private sector. The compulsory and voluntary licensing led to competitive market pricing for the combination treatment of sofosbuvir and daclatasvir which was made available to patients.

In 2016, MOH signed a memorandum of understanding with DNDi to explore new compounds such as ravidasvir resulting in opportunities to conduct clinical trials on the new combination of ravidasvir and sofosbuvir, which is one of the best treatments for hepatitis C due to lower cost and higher efficacy. MOH also worked with the Foundation for Innovative New Diagnostics (FIND) to lower the cost of diagnostics such as rapid test kits. With diagnostics and therapeutics, MOH can scale up testing and treating patients with hepatitis C and decentralize services from tertiary care to primary care. Now, MOH needs to scale up detection of patients with hepatitis C to meet the goal of eliminating hepatitis C by 2030.

In contrast, the scenario 20–30 years ago was tragic as there was no treatment for hepatitis C and patients died prematurely. In the late 1980s, interferon became available, but it showed toxic side effects and only about 50 percent of patients achieved SVR, said Datuk Dr Muhammad Radzi Abu Hassan, National Head of Gastroenterology and Hepatology, MOH.

Sofosbuvir, which has been available in Malaysia since 2018, is a breakthrough in hepatitis C treatment since it’s safe and can cure chronic hepatitis C. Now, the new combination of ravidasvir and sofosbuvir is set to increase cure rates as shown in the STORM-C-1 trial. As a result, liver disease including liver failure, liver cirrhosis and liver cancer can be prevented, said Radzi. “This is the golden opportunity; we have to do whatever it takes to test and treat people with hepatitis C because we have highly tolerable, curative treatment now.”