Gilead: Treating the seven million

Intellectual property disputes in the pharmaceutical industry can sometimes be reported like stories of heroes and villains.

It’s not hard to see why: in the red corner, a multinational pharma giant reporting billions in yearly revenues; in the blue corner, thousands of individuals denied access to life-saving drugs.

In these stories, the patent is the enemy: the barbed wire fence around the drug. But in some situations, patents can be part of the solution to the problem of accessing drugs. Packaged up with some technical know-how, patents can form part of an instruction manual for making cheaper versions of those drugs.

California-based Gilead Sciences has a system for delivering its drugs, which include Viread (tenofovir disoproxil fumarate), Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) and blockbuster Sovaldi (sofosbuvir), to the lowest income countries. Today its HIV medicines reach more than seven million patients in the developing world.

Sovaldi

Since hepatitis C drug Sovaldi received approval from the US Food and Drug Administration (FDA) in December 2013, Gilead has come under fire for the drug’s price—$84,000 for a 12-week course of treatment.

Earlier this year, French healthcare organisation Médecins du Monde (Doctors of the World) filed an opposition against Gilead’s European patent covering the drug. In January, the Indian Patent Office refused to issue a patent covering Sovaldi.

In September last year, Gilead signed a series of licensing agreements with seven Indian generic drug manufacturers, granting them permission to make and sell a generic version of Sovaldi for distribution in 91 lower income countries, including India. Nine months on, those companies are starting to provide cheaper generic versions of the drug.

Providing access

All Gilead’s licensing agreements are through the company’s Access Operations and Emerging Markets programme, established in 2003. Under the programme, Gilead licenses patents and know-how covering its HIV/AIDS and viral hepatitis treatments to about 130 countries that make generic drugs, including those in South America, Africa, and South and South East Asia.

It does this in two ways: either by making its branded product available in those countries under a tiered pricing system depending on factors like healthcare, infrastructure and disease burden, or via its generic licensing agreements. It then receives a royalty to maintain the programme.

Christina Carlson, senior counsel at Gilead Sciences, explains how the licensing process works: “Generic licensees produce and sell their own product under a licence from Gilead so it is their own brand and their own manufactured product.”

She says that there are some quality standards associated with the generic products’ manufacture, but that it is the responsibility of the licensee to get the appropriate regulatory approval to sell its own product in a licensed territory on a country-by-country basis.

It’s a process that can take up to three years, depending on the country and need involved, Carlson explains.

“On Gilead’s part we do a technology transfer so that they can ramp up their technology quickly,” she says.

The companies list the patents that cover their products in their licensing agreements. The scope of the patents involved covers anything necessary for the generic company to exercise its licence, which could involve patents that cover manufacturing methods, Carlson explains.

Gilead also grants rights to the Medicines Patent Pool (MPP), a UN-backed initiative that aims to improve access to affordable HIV medicines in developing countries, to sub-license its patents to generic pharma companies.

"It is the responsibility of the licensee to get the appropriate regulatory approval to sell its own product in a licensed territory on a country-by-country basis."

Under Gilead’s September 2014 agreement, Indian generic drug makers Cadila Healthcare, Cipla, Hetero Labs, Mylan, Ranbaxy Laboratories, Strides Arcolab, and Sequent Scientific were granted permission to make their own version of Sovaldi, and combination hepatitis C drug therapy Harvoni (ledipasvir/sofosbuvir). The companies have set their own prices for the products.

Drugs that may not yet have received FDA approval can be rolled out as generics to countries in need in good time, pending regulatory review.

Gilead’s investigational molecule GS-5816, a treatment for hepatitis C, is undergoing phase III clinical studies in the US, and is being tested in a single tablet regimen with sofosbuvir. In January, Gilead expanded its Sovaldi and Harvoni licensing agreements in India to include the molecule.

Under the agreement, Gilead’s Indian generic partners, which now include Biocon, can make both GS-5816 and a single tablet regimen of the compound and sofosbuvir.

Meeting regulations

Licensing pharma products to a large number of countries that have differing regulatory frameworks or may be lacking in resources is no mean feat.

Some territories require in-country phase III trials before the generic drug can be rolled out, Carlson says, and some countries’ regulatory authorities may also have a backlog or lack the resources to review filings quickly, which can slow things down.

“In these cases, the time between submission of an application and approval, and the review process, can be two or three years,” Carlson says.

Some countries, however, will expedite the generic approval process if the branded product has already received regulatory approval in the territory. Business partners around the world help Gilead register its medicines with national regulatory bodies.

Gilead joined the MPP in 2011, and was the first pharma company to do so. Last July, Gilead granted the MPP a licence to allow generic companies to make tenofovir alafenamide fumarate (TAF), a treatment for HIV/AIDS and chronic hepatitis B.

The agreement lets the MPP sub-license TAF to generic drug makers in India and China, which may then distribute the product to 112 lower income countries.

TAF has been found to be effective in a dose ten times lower than the World Health Organization’s preferred HIV medicine, tenofovir disoproxil fumarate (TDF), meaning that the drug could be more cheaply produced than TDF.

The MPP now has collaborations with Gilead to make generic versions of five HIV drugs: TAF, TDF, Emtriva (emtricitabine), Tybost (cobicistat) and Vitekta (elvitegravir).

Going further

Gilead understands that supplying a drug isn’t the whole battle when it comes to long-term healthcare. Through its work with its generic and other regional distribution partners, it identifies different programmes that educate and promote awareness of disease.

One such programme is its project aimed at entirely eradicating hepatitis C in Georgia by providing free products, creating awareness campaigns and implementing prevention measures. Meanwhile, in Tanzania, Gilead is working with local non-governmental organisations to establish HIV test-and-treat centres.

“We try to identify different ways that Gilead can work with the local community to better assure access to medicines,” Carlson says.

On the pipeline front, Gilead is reporting promising results in clinical studies looking at investigational uses of Sovaldi and Harvoni, even in patients infected with the most difficult-to-treat genotype of hepatitis.

The most recent patent filings suggest that Gilead is exploring a new therapeutic area: how to treat alcohol and drug addiction.

For now, however, Carlson is looking to further expand access to Gilead’s drugs through licensing agreements: “The goal is to file in every country in the world, but we have to prioritise based on prevalence and need.”