The WHO gives the green light to biosimilars, cheap copies of innovative drugs, after a decade of pressure from activists and scientists led from Colombia
It is not common for developing countries to score a goal at multinational pharmaceutical companies. However, that is what happened in April when the World Health Organization (WHO) opened the ban on the production of biosimilars: cheap copies of very expensive innovative drugs. Thanks to the new guidelines of the agency, significant drops in the price of various drugs are expected, including those that act against cancer. This could save the lives of many patients who do not have access to these cures because of their cost, especially in poor countries. The script twist came after a long struggle started a decade ago by a coalition of activists and researchers from the Global South. The group helped dismantle the previous WHO regulation, which put a thousand obstacles to biosimilars. And the pandemic has given the finishing touch, since these drugs could be essential in the response against covid-19.
“The discussion about biosimilars reproduces that of generics 40 years ago: it was said that they were not as good as the originals,” he says. Jaume Vidal, of the NGO Health Action International. Generics are legitimate copies of drugs that are no longer protected by patents – for example, acetylsalicylic acid in Aspirin. After entering the market, prices fall due to the effect of competition. But while generics trace chemicals, biosimilars are imitations of biological drugs. An example is the cancer drug trastuzumab, which contains antibodies that attack cancer cells. “The distinction between generic and biosimilar is purposely made by the industry. Today people know that generics are good and cheap,” he says. Carolina Gomez, advisor to the Secretary of Health of Bogotá (Colombia) and one of the activists for the change of regulation.
A potential to explore
In low- and lower-middle-income countries, patients have to pay out-of-pocket for more than half of the cancer drugs that provide proven benefits, according to a 2017 study from the European Society for Medical Oncology. For many of them, a drop in price may mean having the option of being cured. In Europe, the cost is partially hidden because it is usually assumed by public health, but its spending capacity begins to reach a ceiling due to the escalation of prices of these drugs.
Thus, a biosimilar can cut the pharmaceutical bill in half. For example, in 2015, the Government of Norway achieved a savings of almost 70% after entering the biosimilar infliximab, an antibody that fights autoimmune conditions such as Crohn’s disease and rheumatoid arthritis. What’s more, a study showed that the copy was just as effective as the original. However, despite this enormous potential, “biosimilars are entering the market at a slower pace and with more moderate price drops than generics,” says Gómez. Here are the numbers: in 2017, a quarter of global pharmaceutical sales were of biologics, according to the IQVIA consultancyHowever, biosimilars only accounted for 1% of those sales.
In 2011, Gómez worked in the Ministry of Health of Colombia, under the Government of Juan Manuel Santos. She and Claudia Vaca, a professor of pharmaco-epidemiology at the National University of Colombia (UNAL) and an advisor to the ministry, were the minds that drew up an abbreviated route for biosimilars: a decree that substantially reduced the tests necessary for them to reach the market. The proposal made pharmaceutical companies’ hair stand on end and the matter quickly escalated to high places. So in September 2014, the then Vice President of the United States Joe Biden wrote a letter to Santos alleging that the new regulation threatened health due to the possible entry into the market of dangerous biosimilars due to lack of control. That same year, Santos’ legal advisor refused to approve the decree, arguing that it did not fit with international good practices on biosimilars.
The senior Colombian official referred to the guidelines on these drugs formulated by the WHO in 2009. “At that time, it was not even clear what exactly biosimilars were, there were no regulations,” says Ivana Knezevic, head of the working group on drugs. WHO biologicals. According to these recommendations, it was not enough to demonstrate with analytical tests that the copy was similar to the original and that it was not toxic, a “non-inferiority” comparison with respect to the effectiveness of the original was also required. In other words, a very expensive new clinical trial.
“A barrier to market entry was created that only a small group of large companies could overcome & rdquor ;, he explains. Marcela Vieira, from the Global Health Center, a research center in Geneva (Switzerland). “Because of this regulation, the benefits of biosimilars have been denied to many patients,” he says. Gopakumar Kappoori Madhavan, a Mumbai, India-based legal consultant for the Malaysian NGO Third World Network.
Gómez and Vaca did not resign themselves to the failure of the decree. In May 2014, they brought a proposal to revise the 2009 guidelines to the WHO World Health Assembly. “At that time, Unasur (Union of South American Nations) was strong and got India to join the proposal, “Vaca recalls. The Asian country achieved a diplomatic trade-off: in exchange for unlocking a resolution promoted by the United States, it asked the North American giant to unblock the revision proposal. So that the Assembly ordered the WHO to review its guidelines on biosimilars. When these were suspended, the Colombian decree no longer had restrictions and was approved in September 2014.
In parallel to the political debate, science has been advancing. While you can make fairly exact copies of a chemical compound, the same is not true for the more complex and variable biological molecules. However, “protein analysis methods have improved a lot. It is difficult for us to miss differences that may be relevant to the patient,” he says. Huub SchellekensEmeritus Professor of Pharmaceutical Biotechnology at the University of Utrecht, the Netherlands. A A 2017 study compared the differences between brand-name trastuzumab and its biosimilar, and found that they were the same as between two different batches of the original product. Other 2020 study found that in 95% of biosimilars approved in the EU and the US, comparative trials do not provide any additional information.
Despite these advances, WHO has taken years to modify its guidelines. In October 2018, a committee of experts from the organization limited itself to publishing a question and answer document on said regularization. In May 2019, some 60 NGOs sent the agency a protest letter and a scientific memo demanding a real reform. Among the signers were Schellekens, Gopakumar and Vaca. In September of that year, the three were invited to a session of the expert committee. “It was a weird meeting. There were some aggressive experts, but we broke the political correctness and others [expertos] they began to say that what we were saying was true, “recalls Vaca. Two years later, in April 2021, WHO finally published its proposal for new guidelines. The new regulation opens the door to avoiding costly comparative study: “It will not be necessary if sufficient evidence of biosimilarity can be drawn from other parts of the comparison exercise,” it reads. “Today we understand better what is important in the development of a biosimilar,” explains Knezevic of the WHO.
Gómez and Vaca agree that the covid-19 has given a crucial push. Vaccines are biological products and there are drugs of this class that are candidates for the treatment of the virus. “In a pandemic, the regulatory criteria to approve vaccines were relaxed. How could we be so strict in one subject when we are relaxing so much in another?” The new guidelines are still under discussion and their final publication is expected in the spring of 2022. “I feel great satisfaction. It is good to say: we won,” concludes Vaca.
* This article has been produced with the support of a grant from the European Journalism Center.