On October 1, 2021, the WHO published the new edition of its Model Lists (the EML) of Essential Medicines and Essential Medicines for Children.
The 22nd Model EML includes “new treatments for various cancers, insulin analogues and new oral medicines for diabetes, new medicines to assist people who want to stop smoking, and new antimicrobials to treat serious bacterial and fungal infections.”
Potentially more consequential, the WHO Report “recommended establishing a standing EML Working Group to support the Expert Committee to provide advice to WHO on policies and rules to make highly priced essential medicines more affordable and accessible.”
KEI has long advocated the creation of a category of products that are essential if available at affordable prices, and has called for a new approach to the EML list, which was created in the 1970s when developing countries confronted different challenges in managing drug supplies.
The new working group is tasked with:
- exploration of thresholds at which specific essential medicines become affordable in relation to countries and patients’ ability to pay;
- identification of prices that represent “fair value”for the benefits expected from essential medicines;
- identification of interventions by policy makers and other actors that could facilitate relevant and rapid decreases in prices to reach universal access to these treatments;
- development of a strategy to monitor price and availability trends of essential but unaffordable medicines, to be proposed as part of the next WHO General Programme of Work.
The WHO press release accompanying the release of the new EML highlights a new focus on new products for diabetes including long-acting insulin analogues (insulin degludec, detemir and glargine) and their biosimilars. Among the four new cancer drugs approved is enzalutamide, a drug to treat prostate cancer, invented at UCLA, and marketed globally by Astellas under the trade name Xtandi. KEI was the applicant for listing enzalutamide.
This was the second time that KEI has sought a listing for enzalutamide. A January 2019 application proposed the listing of two drugs, enzalutamide and abiraterone acetate for metastatic prostate cancer on the EML. However, the 21st WHO EML only listed abiraterone. In December 2020, KEI submitted a new proposal for the inclusion of enzalutamide, which was approved.
Enzalutamide is still under patent in the United States (till 2027) and in several other countries, but a number of companies in India sell generic versions. Enzalutamide is also the subject of a compulsory licensing request currently pending before the U.S. Department of Defense, which provided funding for the relevant patented inventions.
The WHO executive summary provided this commentary on the inclusion of enzalutamide:
Inclusion of enzalutamide on the complementary list of the EML, as a therapeutic alternative to abiraterone, for treatment of metastatic castration-resistant prostate cancer. Enzalutamide appears to demonstrate comparable efficacy to abiraterone, has a different mechanism of action and a different toxicity profile, and may be an option for patients unable to be treated with abiraterone. Enzalutamide and abiraterone are both oral treatments but enzalutamide is administered as monotherapy, while abiraterone is co-administered with corticosteroids to reduce toxicity and requires regular monitoring of liver enzymes.The availability of different treatment options with similar efficacy may provide opportunities for countries to negotiate better prices as part of their national procurement processes.
The WHO press release explained that a number of other effective treatments for cancer were considered, but rejected because the drugs are too expensive.
A group of antibodies that enhance the immune response to tumour cells, called PD-1 / PD-L1 immune-checkpoint inhibitors, were not recommended for listing for the treatment of a number of lung cancers, despite being effective, mainly because of their exceedingly high price and concerns that they are difficult to manage in low-resourced health systems. Other cancer medicines were not recommended for listing due to uncertain additional clinical benefit compared with already listed medicines, high price, and management issues in low-resource settings. These included osimertinib for lung cancer, daratumumab for multiple myeloma, and three types of treatment (CDK4/6 inhibitors, fulvestrant and pertuzumab) for breast cancer.
KEI’s Director James Love participated in the WHO’s EML Cancer Working Group, and offers this comment:
“The WHO is in the process of rethinking the Essential Medicines List (EML), and the new list illustrates the challenges it faces. Inclusion on the WHO EML is influential in determining the drugs reimbursed in many countries, including in particular those with lower incomes. The list has been very conservative when it comes to newer products that don’t have low cost generic or biosimilar alternatives. The fact that this excludes many important drugs was made explicit in the new report. The encouraging news is that the WHO is now proposing a significant review of policies to address the effective but expensive category of drugs, including policy interventions that can make products more affordable. WHO members need to support the WHO in this new effort, because it will certainly face opposition.”
For KEI’s earlier calls for reforms of the WHO EML list, see:
- 2021, June 21. KEI statement: 23rd meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines (link)
- 2021, April 29. Making products affordable. Presentation to the WHO Essential Medicines List Cancer Medicines Working Group. (Link)
- 2019, April 1. KEI statement: 22nd meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines (Link)
- 2017, March 27. KEI statement: 21st meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines (Link)
- 2017, October 13. KEI Comments on the Draft Concept Note Concerning the WHO General Programme of Work. (Link)
- 2015, April 17. KEI statement to WHO 20th Expert Committee on the Selection and Use of Essential Medicines. (Link)
- 2011, August 4. Paul Miano. Cancer: Approval, ownership, market structure, and placement on WHO Model Essential Medicines List, for 100 new molecular entities (NMEs) on the NCI alpha list of cancer drugs and vaccines, KEI Research Note 2011:1. (Link)
- 2007, March 2. : Request for changes in the WHO Model EML. (Link)