Milestone development as Novartis signs a voluntary licence for a leukaemia drug with the Medicines Patent Pool, the first such agreement covering a non-communicable disease.
More companies newly engaging in voluntary licences and technology transfers, especially for COVID-19 products – but in a small number of countries.
To address chronic inequity in access to new and innovative medicines, rapid action is needed by pharmaceutical companies to expand access to their on-patent products in low- and middle-income countries (LMICs). Enabling a product to be manufactured by multiple manufacturers is important, and one key way to do this is to engage in voluntary licensing, which can improve availability and affordability in different regions of the world. Non-exclusive voluntary licences (NEVLs) have been used very successfully for HIV and hepatitis, and recently more companies have agreed to NEVLs for their COVID-19 medicines and vaccines. One company has now expanded the use of NEVLs to include a non-communicable disease (NCD) for the first time, with a voluntary licence for a cancer product.
As part of these licensing efforts, pharma companies can carry out technology transfers. This is a crucial additional step companies can take to ensure the uptake and success of NEVLs, and can include, e.g., transferring knowledge on processes such as active pharmaceutical ingredient (API) production, equipment use and raw material handling. Technology transfers can be used to sustainably scale up access in LMICs and ensure that local manufacturers are adequately equipped to efficiently produce high-quality medicines in the long term.
What is a non-exclusive voluntary licence?
A voluntary authorisation given by the patent holder to a generic manufacturer, allowing it to develop and manufacture generic versions of patented medicines. When a licence is ‘non-exclusive’, this means that the patent holder can issue licences to multiple manufacturers, often in different countries. The Medicines Patent Pool (MPP) is a key organisation that can facilitate this.
First voluntary licence for a cancer medicine
Significantly, during the period of analysis, Novartis announced plans for a NEVL covering nilotinib (Tasigna®), a medicine indicated for chronic myeloid leukaemia. This drug had been on MPP’s Priority List,* and an agreement with the MPP was ultimately signed in October 2022.
This is the first time that the use of NEVLs has expanded beyond products or compounds targeting communicable diseases – specifically HIV, hepatitis, tuberculosis and COVID-19 – and is a particularly hopeful sign as the burden of NCDs, such as cancer and diabetes, is rising globally. In 2030, around three-quarters of deaths from cancer are expected to occur in LMICs, yet essential on-patent oncology medicines are often unavailable or unaffordable in these countries.
The potential impact of the NEVL will be limited by the fact that it does come less than a year before the expiry of the main patent for nilotinib (Tasigna®). In addition, Novartis had previously chosen not to file for patents in several of the countries included in the NEVL. However, if generic medicine manufacturers do take up the opportunity offered by Novartis via MPP, this agreement could accelerate the expansion of availability and affordability of this cancer drug – which is classed as an “essential medicine” by the World Health Organization – to patients living in LMICs. It also sets a precedent for other companies to sign NEVLs for medicines targeting NCDs. Novartis has committed to reinvesting all royalties from this agreement into the Access to Oncology Medicines (ATOM) Coalition, a new global initiative launched in 2022 to sustainably expand access to quality-assured essential cancer medicines in low- and lower-middle income countries.
The rise of NEVLs, driven by COVID-19
Companies including AstraZeneca, Eli Lilly, GSK, MSD, Novartis and Pfizer entered into new licensing agreements during the period of analysis, with ten of the companies in scope now engaging in at least one voluntary licence – up from seven in the previous Index. The number of licensed compounds has risen from 22 to 27.
Much of this trend is driven by companies engaging in voluntary licensing for COVID-19 products. Out of the eight companies in scope with COVID-19 products in their portfolios, four companies now have at least one NEVL (and one further company has a private voluntary licence, not analysed here). MSD agreed to a NEVL with the MPP before the launch of its oral antiviral molnupiravir (Lagevrio®), as did Pfizer for nirmatrelvir/ritonavir (Paxlovid®). Gilead signed a royalty-free voluntary licensing agreement and carried out a technology transfer for the manufacture of its injectable antiviral remdesivir (Veklury®) in India, Egypt and Pakistan. Eli Lilly signed a royalty-free NEVL with Cipla, Sun Pharma, and Lupin covering its COVID-19 treatment baricitinib in India. In addition, for its COVID-19 vaccine (ChAdOx1-S [recombinant]) (Vaxzevria), AstraZeneca has engaged in a sequence of exclusive voluntary licences (rather than NEVLs) in different parts of the world.
Quality and scope of voluntary licensing agreements
At least 80% of the countries in scope of the Index are covered by at least one of the four NEVLs for COVID-19 products, with India included in the greatest number (three). If a country is covered, that means generic versions of the originator product can be introduced in that country; it does not, however, mean that generic medicine manufacturers have taken up the licence, or that the product is actually being made available to people living in that country.
While companies’ engagement in NEVLs and their commitments not to file or enforce patents in particular countries can lead to positive outcomes for access, the gold standard is to back up this approach with technology transfers. Yet, although many countries are covered by NEVLs for COVID-19 products, actual technology transfers – with specific generic medicine manufacturers – have been carried out in just a handful of countries, as seen in the map below.
Companies have demonstrated growing willingness to engage in voluntary licensing. However, the momentum must continue - with more NEVLs for more products, from more companies, covering a wider range of diseases and countries, earlier in products’ lifecycles, and with access-oriented clauses. This will be especially important in the context of novel therapies and NCD medicines. Companies can also expand the geographic scope of existing NEVLs, especially to include more upper-middle income countries, which are often excluded from these agreements.
Companies should take advantage of existing resources to guide their licensing decisions, such as the MPP’s list of medicines that should be prioritised for NEVLs, which included Novartis’s nilotinib at the time of signing.* Companies with other products on the priority list can take similar actions, such as Boehringer Ingelheim with empagliflozin (Jardiance®) and AstraZeneca, with its lung cancer treatment osimertinib (Tagrisso®). Companies can also supplement current and future NEVLs with technology transfers and other capacity building efforts.
*Medicines Patent Pool. Prioritisation of medicines for in-licensing by the Medicines Patent Pool. MPP; 2022. Accessed 01/11/22: https://medicinespatentpool.org/what-we-do/%20prioritising-medicines-for-licensing