Gilead’s MPP license for tenofovir alafenamide (TAF) patents

On July 24, 2014, the Medicines Patent Pool announced welcome modifications and expansions of their licensing agreement with Gilead. Among the significant changes were the addition of a new drug, tenofovir alafenamide (TAF), formerly known as GS-7340. TAF is a nucleotide reverse transcriptase inhibitor, and a prodrug of tenofovir. TAF is considered to have similar antiretroviral efficacy to tenofovir disoproxil fumarate (TDF), the drug it may replace in use, but can be administered with smaller doses and with less adverse effect on kidneys and bones.

“Gilead Sciences’ tenofovir is highly effective and a recommended component of first-line HIV treatment, but it can cause impaired kidney function and bone loss in some people. Moreover, it is not very bioavailable. TDF (Viread, also in the Truvada, Atripla, Eviplera/Complera and Stribild co-formulations) is a pro-drug that delivers tenofovir diphosphate, the active form, efficiently to blood plasma.

TAF has a different structure to TDF and is metabolised by a protein known as cadapsin A, reaching higher concentrations in lymphoid cells such as CD4 cells. With the new formulation, adequate tenofovir concentrations in cells can be achieved using a much lower dose, which has less potential to harm kidney and bone tissue.” [Liz Highleyman, New pro-drug tenofovir alafenamide appears equally effective but better tolerated, NAM AIDSmap. March 7, 2013]

According to the report from the MPP’s Expert Advisory Group:

“TAF is an alternative pro-drug of tenofovir that is currently in phase III clinical trials for the treatment of HIV and hepatitis-B viral infection (HBV). This new pro-drug allows TAF to be dosed at much lower levels than TDF; it is being investigated at less than one-tenth of the 300mg recommended daily dosage for TDF. Because of the lower dosage, TAF can potentially be manufactured at a much lower cost than TDF, while also potentially offering significant clinical benefits, such as reduced side effects and toxicity, and easier formulation into fixed does combinations.

The MPP informed the Expert Advisory Group (EGA) that the TAF patent has been granted in several key jurisdictions, including India, China, ARIPO, OAPI and South Africa.”

The licence will allow manufacturers in India and China to develop generic versions of TAF for 112 countries in the developing world. However, technically the MPP license does not permit a generic manufacturer to sell TAF (or the other Gilead products) in China, even though they can be manufactured in China. This seems to invite China to grant a compulsory license on the relevant patents for the Gilead drugs included in the license.

Given the focus of the MPP on HIV, and the discussions at UNITAID and the MPP over Hepatitis, It is significant that the Gilead license specifically includes a field of use for both TDF and TAF to treat hepatitis B.

“Field” shall mean the treatment and prophylaxis of HIV infection, provided, however, that (a) for Product containing TDF as its sole active pharmaceutical ingredient, the Field shall include the treatment and prophylaxis of Hepatitis B Virus infection, and (b) for Product containing TAF, EVG or COBI, the Field shall include any use that is consistent with the label approved by the FDA or applicable foreign regulatory authority for the use of such Product containing TAF, EVG or COBI, including if so approved, for the treatment and prophylaxis of Hepatitis B Virus for TAF.”

KEI is impressed at the recent additions to the MPP license portfolio, including the new agreements with Gilead, ViiV (GSK and Pfizer), Bristol-Myers Squibb and Roche. The fact that both Gilead and ViiV are licensing their newest HIV drugs to the MPP is particularly encouraging, and comes at a time when there are huge challenges providing sustainable access to medicine for HIV in developing countries. KEI encourages Abbott/AbbVie, Merck and Johnson and Johnson to engage and conclude licensing agreements with the MPP.