DNDi Begins Quest For Sub-$200 Hep C Combo With Malaysia Trial Plan

DNDi is implementing a major new initiative in hepatitis C through a collaboration with Malaysia's Ministry of Health that aims to begin clinical trials this year to investigate new "affordable" direct-acting combination therapies, with the ultimate of getting the cost of a 12-week course to below $200.

The Drugs for Neglected Diseases initiative (DNDi) and the Ministry of Health in Malaysia are initiating work under a recent formal agreement to begin assessing highly effective but lower priced new drug combinations for hepatitis C.

"At present, the plan is to test both an approved treatment regimen and a promising new regimen in order to demonstrate treatment options that are safe, effective and affordable," DNDi's regional communications manager in India, Manisha Sharma, told PharmAsia News.

More information on specific treatments will be disclosed once agreements with partners have been closed, she said.

The formal Malaysian alliance, signed earlier this year, marks the launch of a wider five-year global access project for hepatitis C by DNDi, a not-for-profit public-private R&D partnership working internationally across various neglected disease areas.

In line with this, the initial focus in Malaysia will be on expediting local Phase III clinical trials with promising new treatment regimens combining new direct-acting antiviral agents, and the expansion of access to treatments as part of a "public health approach" to the disease.

In a briefing document on the initiative, DNDi states that the combination of most early interest is that of the nucleotide analog sofosbuvir (Gilead Sciences Inc 's Sovaldi) and the NS5A inhibitor daclatasvir (Bristol-Myers Squibb Co.'s Daklinza), with the aim of establishing pan-genotypic activity in Asian HCV populations over the next few years.

The first clinical trials under the initiative should be launched at multiple sites in Malaysia later this year, co-sponsored by DNDi and Clinical Research Malaysia, a non-profit body wholly owned by the country's Ministry of Health set up to attract clinical studies to the country and to build local capabilities.

Public Health Approach

The ministry said the results from the studies would enable "informed and appropriate policy and economic decisions on adopting these regimens as a public health tool in Malaysia."

Although there is no word on reimbursement policy at this stage, Minister of Health Dr. S. Subramaniam said that any such treatments would be "scaled up" in a program that would also include new advocacy efforts to help prevention.

In Malaysia, the aim is to conduct the collaborative trials as part of the envisioned public health approach to hepatitis C, within the framework of the country's National Strategic Plan on viral hepatitis.

This began to take shape last year and follows a similar plan for HIV/AIDS, the objective being to draw up comprehensive measures for screening, prevention, diagnosis and treatment.

As envisioned by DNDi, the public health approach includes simplified care models involving primary care facilities, and reduced dependence on genotyping and viral load determination.

The primary overall objective, the partners say, is "ensuring equitable access to affordable and effective treatments for patients suffering from this disease in Malaysia."

DNDi and the ministry pointed to the rising local burden of hepatitis C, stressing that treatment scale-up is necessary to address the steady rise in cases. As of 2009, there were already around 454,000 people living with the disease in Malaysia, where close to 3% of the 15-64 population is estimated to be infected with the virus.

Malaysia, some other Asian countries including Thailand, and parts of China, have a particularly high prevalence of genotype 3 HCV, for which the sofosbuvir/daclatasvir combination is effective.

BMS recently unveiled results from its Phase III trial with daclatasvir that included sites in China (Also see "BMS Unveils Asian HCV Combo Data As China Plans Progress" - Scrip, 22 Feb, 2016.).

Broader Plans, Pricing Targets

DNDi's broader, five-year global access plan for hepatitis C also includes similar clinical trials in Thailand that will look more closely at whether new drug combinations can be made broadly available "at an affordable price."

In the longer five-year term, the hope is to license pipeline compounds from patent holders as well to facilitate novel regimens, in addition to drugs that may already have been commercialized.

In its project briefing document, DNDi points to the high efficacy of new direct-acting antiviral agents but adds that the pricing of those already on the market is "exorbitant", making them inaccessible to most patients.

Inter-company competition has prevented the timely development of combinations for public health use, it argues, particularly in middle-income countries not covered by developers' "not transparent" generic production and access schemes.

Of these, one of the biggest involves Gilead's licensing of sofosbuvir to seven generics firms - including several in India - in September 2015, in a deal for manufacturing and supply covering 91 developing countries (Also see "Gilead Signs Generics Pact For Sovaldi In Developing Countries" - Scrip, 15 Sep, 2014.).

Both Malaysia and Thailand were excluded from this deal.

While sofosbuvir and daclatasvir are already approved in various markets and have very high efficacy, DNDi believes the manufacturing cost of the combination could be driven down to price points of under $166 for a 12-week course.

In the US, Sovaldi was launched at a price of around $1,000 per pill, equating to $84,000 for a 12-week course.

DNDi sees access to new direct-acting drugs coming about through a variety of means, including price negotiations or licensing agreements with originators, and access to generic versions resulting from controlled licensing agreements.

It also notes that a number of patent oppositions are underway and the option of exploiting the World Trade Organization's TRIPS flexibilities to enable generic production or import for public health reasons.

"DNDi's R&D activities will complement all of these strategies," it said.

In total, €25m ($27.1m) has been budgeted for the DNDi hepatitis C project over five year, with both Malaysia and Thailand committed to contributing resources.