A Followup on Lenacapavir: Gilead enters into Voluntary Licensing Agreements in 120 LMICs

Just a day after our update on the Lenacapavir patent oppositions (here), Gilead has signed “Royalty-Free Voluntary Licensing Agreements” (VLAs) (pdf) with generic manufacturers aimed at boosting HIV prevention in “high-incidence, resource-limited countries.” The focus is squarely on low- and middle-income countries (LMICs), as highlighted in Gilead’s official reports (here) and various media outlets (here). This strategic move reflects Gilead’s commitment to expanding access to vital treatments where they’re needed most, and this post will fact-check the coverage of these VLAs and the extent of the veracity of Gilead’s claims.

A Look into Lenacapavir’s VLAs 

As anticipated in the previous post, Gilead has licensed Lenacapavir. It did so to six pharmaceutical manufacturers—Dr. Reddy’s Laboratories, Emcure, Eva Pharma, Ferozsons Laboratories, Hetero, and Mylan—to produce and sell generic versions in 120 high-incidence, resource-limited countries, primarily low- and lower-middle-income nations. These VLAs were strategically signed before any global regulatory submissions, allowing for a swift introduction of generics upon approval. This collaborative approach appears to foster goodwill, particularly as it addresses the troubling history of LMICs being overlooked in previous VLAs for essential medications, including those for HIV.

In its official release, Gilead emphasised that the selection of these six partners was based on rigorous criteria to ensure high-quality production. They considered each partner’s track record with generic medicines and sought input from global health advocates to promote international collaboration. This focus on quality is crucial for the successful rollout of Lenacapavir in these regions.

Additionally, the chosen licensees are set to rapidly build manufacturing capacity, while Gilead aims to prioritise registration in 18 countries that account for about 70% of the global HIV burden until generics become available.

However, it’s essential to examine the extent of the coverage offered by these voluntary licensing agreements. The Draft of the Lenacapavir VLA lists the 120 countries involved and highlights the target 18 [Appendix 1]. If this aligns with the 2024 HIV case data, concerns regarding the restrictive nature of VLAs for HIV medications in light of Lenacapavir’s patent might be alleviated. This would indeed represent a significant positive step forward in addressing HIV prevention in resource-limited settings.

Fact-Checking Lenacapavir’s VLAs 

Using the HIV Rates by Country 2024 report from the World Population Review (here), let’s compare the extent of the VLAs inclusion as per the rates of HIV prevalence, which not to anyone’s surprise, is overwhelmingly in LMICs:

When looking into the top 10 Countries with the Highest HIV Rates (%), we can observe that:

Moreover, when we come to the top 10 Countries with the Most HIV Cases, the situation is such:

Looking at the top 10 countries with the highest HIV rates and incidences, it’s clear that the majority of these nations fall within the VLA framework. This coverage is commendable, as it targets areas that need it most.

However, the exclusion of Brazil from this list is concerning, especially since it qualifies as an LMIC and has historically been overlooked in similar agreements for essential medications (as discussed here and here). A database by LAPaL (here) shows that a patent has been granted in Brazil for the Lenacapavir compound, been granted and is not in force for Lenacapavir and analogues (Markush formula), while the patent grant for Crystalline forms of Lenacapavir sodium salt makes no mention for Brazil.

Additionally, while China isn’t classified as an LMIC, its significant HIV burden warrants consideration, yet it’s also absent from the VLA coverage. Russia, with its considerable HIV incidence, similarly lacks inclusion. LAPaL’s database shows a grant of a patent for Lenacapavir compound done in China, a pending application for a patent for Crystalline forms of Lenacapavir sodium salt, and granted and not in force for Lenacapavir and analogues (Markush formula). The pending application for a patent in China shows no PGOs filed against the patent as per the PCT website.

Some other interesting aspects of the VLAs can be the limitations taht it does impose on the licensees.  For instance, clause 2.5 puts a clause for “Limitations on Product Combinations” i.e. license not to sell products in combinations with other drugs. Moreover, Licensee is allowed to sell the Product in their designated territory through Gilead Distributors, but only within the Territory and cannot import or sell outside it. Gilead Distributors can only sell to Customers in their designated countries, and Third Party Resellers are subject to the same conditions. As per clause 3.2, the licensee can’t source Lenacapavir or related materials from Gilead Suppliers without Gilead’s prior written consent. Clause 7.2 again puts a restriction on the diversion of Products and Technology. As per clause 3.4, licensees can’t enter or amend agreements for supplying intermediates, Lenacapavir, or packaging components without Gilead’s prior written approval. Clause 5 specifically deals with managing Gilead’s IPRs by the licensees.

Despite the exclusions for some countries and limitations in the VLAs, the overall scope of the VLAs is a positive development, particularly for India, which stands to benefit from increased access to Lenacapavir. While the omissions raise valid concerns, the focus on enhancing access in high-burden LMICs represents a meaningful step forward in the fight against HIV. Nevertheless, let’s wait and see how the pre-grants unfold.