We need a global system for testing and approving cancer treatments

The lack of an international system for approving new cancer therapies under clinical trials is costing up to 2 million lives a year, according to research conducted by the authors. In this article, they recommend five steps for harmonizing country regulations. Doing so, they say, would allow clinical trials in all participating nations to follow the same criteria. The drugs would be approved more quickly and become available to more patients sooner, which would extend the lives of those in critical need of care.

Thanks to the global harmonization of regulations for the approval of cancer therapies subject to clinical trials, it would be possible to reduce the number of global cancer deaths per year by 10% to 20%, or from 1 million to 2 million lives. This is because the lack of such an international system is slowing the approval of treatments around the world, according to research we have conducted.

The United States has already made significant progress in creating an international regulatory infrastructure for the simultaneous review and potential approval of new cancer treatments with Project Orbis, an initiative of the Food and Drug Administration’s (FDA) Cancer Center of Excellence. . The task ahead is to take that picture and further internationalize it. The goal would be for clinical trials in all participating nations to follow the same criteria, which would allow a company applying for an anticancer drug approval to submit a series of applications to the regulatory authorities of those countries, allowing for such regulators to review these questions at the same time and facilitate a dialogue with each other on how to improve global clinical trials. Drugs would be approved faster, they would become available to more patients sooner, which would extend the lives of those in critical need of care.

We assessed how simultaneous international regulatory approvals of two specific drugs would benefit patients around the world. The first was pembrolizumab, which the FDA approved in 2016. It is a type of immunotherapy used to treat patients with metastatic non-small cell lung cancer (NSCLC), the most common type of lung cancer, whose tumors express a protein, PD-L1. As the first immunotherapy approved as a front-line treatment option for lung cancer, pembrolizumab changed the therapeutic landscape for patients: the Phase III study found that for patients with tumors that had high PD- expression L1 (approximately 30% of cellular lung cancers), pembrolizumab reduced the risk of death by 38% compared to chemotherapy, and patients who took it lived an average of 13 months longer with nearly a third of patients still alive to five years after starting treatment for stage 4 lung cancer.

But the approval was confined to the United States. The drug has been delayed in approval in other countries and is not yet available in many countries. Based on a retrospective analysis, we estimate that over 600,000 years of patient life could have been saved in the six countries and regions with the highest cancer burden (Japan, European Union (EU), Brazil, Canada, India and China) if pembrolizumab was approved worldwide at the same time it was approved in the United States. This translates into nearly 850,000 years of life when scaled across the global patient population.

The second treatment we looked at was enzalutamide, an androgen receptor inhibitor for prostate cancer. This is the second most diagnosed cancer and the fifth leading cause of cancer mortality among men globally. The FDA first approved enzalutamide in 2012 for patients with metastatic castration-resistant prostate cancer (mCRPC), an advanced stage of prostate cancer. The drug significantly improved patient outcomes: the phase III study showed an incremental overall survival benefit of 4.8 months, on average, compared to placebo. However, internal regulatory delays have occurred in other countries. We estimate that 284,000 years of patient life could have been saved in Japan, the EU, Brazil, Canada, India and China if enzyme was approved globally at the same time it was approved in the United States.

China offers the greatest opportunity. It is estimated that 500,000 years of patient life could be saved through harmonization of testing requirements that have delayed patients’ access to care by patients in that country. For example, enzalutamide was not approved in China for mCRPC until November 2019, seven years after the US approval. The delay was largely driven by a separate Asian multinational phase III study that was conducted to meet China’s specific regulatory requirements. This delay illustrates the importance of greater standardization and acceleration of global regulatory processes. In recent years, however, China has made great strides in speeding up drug approvals. For example, as part of regulatory reforms, the requirement for China-specific trials was lifted on the condition that the foreign pharmaceutical manufacturer conducted international, multi-center trials that included China as a site.

Globally, there are nearly 10 million cancer deaths per year. The FDA has approved about seven new cancer drugs each year. In our study of pembrolizumab and enzalutamide, we calculated the time gap between FDA approval and approvals in the countries with the highest cancer burden in each of the subpopulations indicated on their labels. We then calculated the potential life years that can be saved in each country, based on cancer mortality, overall survival benefit, and approval time gap in each subpopulation. Extrapolating from the results of these two drugs, we estimate that with international standardization and simultaneous approvals, each of the seven drugs per year would help, on average, 10% of all cancer patients reduce their risk of death by 10% to 20%. This translates into 1 to 2 million lives per year.

To start building such an international system, we recommend that countries around the world take the following steps:

Strengthen regulatory bodies. This is where the further internationalization of Project Orbis comes into play. In many countries, regulators have minimal capacity to evaluate and process drug approvals. This shortage of manpower and regulatory infrastructure results in longer waiting periods. Funding and training provided by countries with more developed regulatory systems for countries with less developed regulatory bodies could improve and extend the lives of cancer patients around the world.

Preliminarily define the requirements for ethnicity-specific tests. Asia Pacific countries often require their local patient populations to be represented in global study data. This is less relevant for some drugs, but may be necessary for some small molecule drugs whose dosage regimen varies based on sensitivity in different populations. Regulators should define in advance which trials need this kind of consideration, so that they can be incorporated simultaneously, thus preventing delays.

Standardize production inspections. As part of the approval process, regulatory agencies in some countries require production inspections that take time to plan and conduct. We suggest disseminating international guidelines that can be adopted by all countries so that country specific requirements in this area do not cause unnecessary delays in approvals and processing.

Plan for approval in secondary markets. Companies should design their strategies for obtaining approvals and developing and commercializing treatments in markets outside the United States early in the research and development process, prioritizing countries with the highest unmet need. This involves understanding country-specific regulatory requirements in advance and strategically designing pivotal evidence to facilitate faster international approvals.

Reform insurance coverage for life extension treatments. In addition to regulatory harmonization, reform of drug prices and drug insurance coverage is essential in many countries. Unlike in the United States, where insurance coverage often immediately follows regulatory approval, coverage in many other countries is at the discretion of multiple stakeholders. In the European Union, for example, while regulatory approval applies to all 27 member countries simultaneously, a drug cannot be used in individual countries until each nation has conducted its own price negotiation, which can take up to a year. These processes should be streamlined so that patients can access medications more quickly.

We are under no illusions: we realize that making the changes we recommend would require more effort. But given the stakes – the 10 million lives lost to cancer each year globally – it would certainly be worth it.

The authors would like to thank the contributions to this manuscript by Clare Teng, Lillian Zhu, Johanna Costigan and members of the Bloomberg New Economy International Cancer Coalition, a multi-stakeholder group of public and private sector leaders aiming to explore ways to drive better collaboration. international to accelerate the development and approval of cancer treatments and prevention and to improve patient access around the world.

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