NEW YORK – At a major medical conference in Europe where drugmakers and researchers celebrated the latest advances in cancer treatment, Andre Ilbawi from the World Health Organization (WHO) acknowledged the sober reality that the "vast majority" of cancer patients around the globe don't have access to essential medicines.
"When we look at why, it's not simple," Ilbawi, a leader within the WHO's cancer program, said at the European Society for Medical Oncology Congress in Barcelona, Spain, on Saturday. The cost of medicines always comes up first, he noted, but it's much more complex than just an "affordability problem" and will take partnerships to come up with solutions tailored to the needs and challenges of specific countries.
Ilbawi cited Genentech's HER2-targeted drug Herceptin (trastuzumab), which was first approved in the EU in 2000 for treating HER2-overexpressing breast cancer, as a prime example of the disparity in patients' access to essential cancer medicines around the world. Since 2015, Herceptin has been on the WHO's essential medicines list based on data showing that the 20 percent of breast cancer patients with HER2-overexpressing tumors don't live as long and have a worse prognosis if they don't receive this personalized drug. The WHO's essential medicines list is a roster of drugs that the organization recommends healthcare systems prioritize for patients.
Herceptin "was a game changer. It totally revolutionized our approach to cancer therapy," Ilbawi recalled, adding that when the data first came out on Herceptin's benefit, "if we asked [the attendees] at those conferences years ago, 'How many people will have access to trastuzumab by 2024,' I'm sure all of us would have said, '100 percent' or '90 percent.' Of course, it's an essential medicine."
And yet, 25 years after this breakthrough product first came on the market in the EU, a rough estimate based on parameters the WHO uses to measure the accessibility of medicines is that between 20 percent and 40 percent of breast cancer patients around the world have access to Herceptin. "What a travesty in the public health agenda for cancer," bemoaned Ilbawi.
When gauging whether a treatment is accessible to patients, the WHO considers several factors, for example, whether the medicine is included in a country's essential medicines list, if it's included in treatment guidelines, and if the country can procure enough medicine to supply it to the population that needs it, as well as the affordability of the medicine based on its price, the availability of generics, and inclusion in benefits packages. Medicines are accessible when they're both available and affordable, noted Ilbawi.
In the case of Herceptin, according to a comparison of 137 countries' essential medicines lists published in 2019, only 35 countries, or 26 percent, included Herceptin. And while other countries may recommend Herceptin for HER2-positive breast cancer in treatment guidelines because the WHO deems it an essential medicine, it still may not reach patients.
"Maybe it's in the essential medicines list, but it's not in the guidelines. Maybe it's in the guidelines, but it's not reimbursed. … Maybe it's in the essential medicines list and in the guidelines, but who pays for it? We don't know," Ilbawi said, underscoring how "policy incoherence" is a major reason patients in low- and middle-income countries can't access essential medicines like Herceptin.
It's not uncommon for other countries to copy guidelines from organizations like ESMO, but those guidelines may not be applicable for patients in sub-Saharan Africa and other low- and middle-income countries, he continued. And even when the governments of these countries put essential medicines like Herceptin on their essential medicines list, the lack of infrastructure for forecasting demand for these drugs and procuring enough stock can hinder accessibility.
Botswana, a middle-income country of 2.6 million people in sub-Saharan African, did put Herceptin on its essential medicine's list in 2015, when the WHO added the drug to its list. However, an evaluation of the availability of chemotherapy drugs on Botswana's essential medicine's list showed that there were significant stock outs that affected patients' access to common cancer drugs, including Herceptin. This meant that patients during the time when Botswana's treatment centers didn't have supplies of Herceptin and other essential drugs, cancer patients were getting suboptimal treatment, delaying therapy, missing doses, or getting less efficacious or more costly alternatives.
Another analysis published in 2018 showed that Botswana spent nearly $1.0 million out of $2.34 million in its cancer medicines budget, or 43 percent, to procure Herceptin for 5 percent of its population. "It's quite difficult to answer if this is right or wrong," Ilbawi said. "We applaud Botswana for making [Herceptin] available, but these trade-offs aren't easy for anyone, for providers or for [government] budget planners."
When the WHO looked at the broader questions of how essential medicines like Herceptin are being paid for, they found that 60 percent of low- and middle-income countries' governments do not include the HER2-targeted drug in their benefits packages. This means that "the purchasers in most countries around the world are families and their communities," Ilbawi said.
In countries without health regulators that determine the essential medicines for the population or health technology assessment (HTA) bodies that identify the drugs that are cost-effective for the government to fund for patients, Ilbawi noted that patients and families are often left on their own to decide if they can afford to pay for the drugs that their doctors recommend, which is not always guided by the best available evidence. "This is happening to my family in the Middle East [and] to people around the world," he said, adding that people are experiencing significant financial toxicity, losing homes and assets, in trying to access cancer medicines.
"All of a sudden the patient is the HTA, the patient is the regulator, the patient is the appraiser, and if they do decide to purchase that medicine, just imagine the consequences," Ilbawi said. "This is generational poverty that we're talking about. This is not right."
The lack of quality of cancer drugs in low- or middle-income countries has also been problematic. The WHO estimates that around 10 percent of medicines in low- and middle-income countries are fraudulent or substandard. In 2014, for example, the European Medicines Agency alerted healthcare professionals in the EU to be on the watch for vials of Herceptin that had been stolen in Italy, tampered with, and reintroduced into the supply chain. Investigations subsequently uncovered other cancer drugs that had been similarly stolen, falsified, and reintroduced on the market.
When the WHO spoke to health systems in low- and middle-income countries, it became clear that they often have little visibility into the supply chain for procuring medicines, having purchased them from wholesalers and pharmacies. Such quality and supply chain issues have "a very real impact" on communities around the world, Ilbawi said, adding that it's not enough for medicines to be available, but the available drugs must also be quality assured.
Even though patients' lack of access to essential medicines around the world may seem like an intractable problem, as a self-proclaimed optimist, Ilbawi highlighted several reasons for hope. For example, the entrance of biosimilars is pushing down the cost of some essential medicines. Since the patent expired for Herceptin in Europe in 2014, several trastuzumab biosimilars have entered the market.
According to one cost comparison model published in 2019, the projected costs for hospitals to give subcutaneously injected Herceptin was €17,929 per patient (approximately $19,873 based on currency rates as of September 15) versus €8,499 per patient to administer Amgen's intravenously infused trastuzumab biosimilar Kanjinti. The cost difference, noted the authors from Amgen and a hospital in Italy, was largely driven by the price of the drugs, which they estimated as €21,497 for subcutaneous Herceptin and €12,012 for intravenous Kanjinti based on publicly available data.
"Now, after decades, we're starting to see the sales price of trastuzumab come down," Ilbawi said. "And that is an opportunity for us to see whether availability in low- and middle-income countries will improve."
But he cautioned that focusing just on affordability and pricing won't address the underlying, multifactorial problems at every stage of the life cycle of essential medicines that keep them from patients. The WHO is developing tools and platforms to help countries address challenges from the beginning to end of the treatment life cycle, from access to clinical trials to pharmacovigilance systems that ensure medicines are safe.
"Increasingly, we're working with countries to support these platforms being made available," Ilbawi said.
He highlighted that the WHO is conducting research to gain more detailed insights into the lack of clinical trial access for cancer patients in low- and middle-income countries, including assessing their needs for new medical products and formulations. This is a big focus area at the WHO, he said, and there are efforts underway to create research priorities for patients around the world, not just in high-income countries where nearly 70 percent of trials take place.
The WHO is also working with governments to model the budget impact of providing essential medicines recommended in their treatment guidelines, which in turn helps health systems set priorities. The organization has also developed tools for countries that allow them to better forecast the need for medicines and procure them, and it is helping countries set up regulatory bodies that don't have them so there is better assurance of the efficacy and safety of medical products.
"Decisions have to be made based on country-specific priorities," Ilbawi said, underscoring the importance of working within partners to come up with local solutions to the access problem. For example, in Kazakhstan, Ilbawi recounted how the WHO helped the government update treatment guidelines, improve clinical adherence, and increase the number of medical products on the essential medicines list available to patients there. He noted that the WHO is working with ESMO to do the same for other countries.
"There are better days ahead if we make strategic decisions as a community and see this as a problem we can all solve," Ilbawi said, inviting the broader oncology community at the ESMO Congress to get involved in these discussions and efforts. "We're quite hopeful, and dare I say optimistic, about the future."