Lack of global regulatory coordination for cancer clinical trials costs 1.5 million lives a year despite therapies being available

The Bloomberg New Economy International Cancer Coalition says Pembrolizumab and Enzalutamide could save millions of lives in Japan, the European Union (EU), Brazil, Canada, India, and China if patients were able to be treated with the drugs

NEW YORK, Oct. 18, 2022 /PRNewswire/ -- A new study by members of the Bloomberg New Economy International Cancer Coalition (the Coalition) says that at least 1.5 million deaths (representing 20 percent of global cancer deaths) from cancer could be avoided each year if international regulations around patient trials were more standardized and people placed on live saving treatment such as Pembrolizumab and Enzalutamide.

The study was published in the Harvard Business Review today ahead of the World Cancer Congress convened by the Union for International Cancer Control (UICC) taking place in Geneva, Switzerland this week. It analyzed how the simultaneous international regulatory approvals of these two specific drugs would have benefited patients around the world. It argues that despite Food and Drug Administration (FDA) approval of Pembrolizumab in 2016 and Enzalutamide in 2012, neither drug is yet available in many countries and regions of the world due to regulatory isolationism that is preventing approval and usage of these and other much-needed oncology therapies. While regulatory challenges represent only one issue, in addition to other obstacles such as market access, changes in this area could result in meaningful advancements for patient care.

"This would allow for clinical trials in all participating nations to follow the same criteria, significantly increasing available datasets and expediting the clinical trials as a result. Also, these initiatives would lead to a faster dug approval and prolong the lives of those who are in critical need of treatment," said ICC member Mary Gospodarowicz who is Professor of Radiation Oncology at the University of Toronto, former Medical Director at the Princess Margaret Cancer Centre and a past president of the UICC.

The Coalition was launched last year at the Bloomberg New Economy Forum with the aim of promoting discussion around a reimagining of patient-centric cancer clinical trials on global health agendas. Its members include representatives from regulatory bodies, patient advocacy groups, industry, and researchers and academics from major cancer centers and universities worldwide. Pharmaceutical company AstraZeneca has just been announced as the latest member to join the group.

"Cancer treatments are advancing every day, and they shouldn't be held up at such high costs," said Michael R. Bloomberg, founder of Bloomberg LP and Bloomberg Philanthropies. "The more that countries come together and collaborate, the faster that patients around the world can access life-saving care."

Pembrolizumab is 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 front-line treatment option approved for lung cancer, Pembrolizumab changed the treatment landscape for patients: a Phase III trial found that for patients with tumors that had high expression of PD-L1 (about 30 percent of advanced non-small cell lung cancers), Pembrolizumab reduced the risk of death by 38 per cent compared to chemotherapy, and patients who took it lived approximately 13 months longer.

But the approval was confined to the United States. Despite significant patient impact, the drug experienced approval delays outside the U.S.—and it is still not available in many countries. Based on a retrospective analysis, the Coalition estimates that over 600,000 patient life-years could have been saved in the six countries and regions with the highest tumor burden (Japan, the European Union (EU), Brazil, Canada, India, and China) if Pembrolizumab had been approved worldwide at the same time it was approved in the U.S. This translates to almost 850,000 life-years when scaled to the global patient population.

The analysis calculated the time gap between the FDA approval and approvals in countries with the top lung cancer burden and then estimated lung cancer mortality in the corresponding year, and the sub-population addressable by the approval.

A similar scenario has played out with Enzalutamide, an androgen receptor inhibitor for prostate cancer, the second most diagnosed cancer and fifth leading cause of cancer mortality among men globally. Enzalutamide was first approved by the FDA in 2012 for patients with metastatic castrate resistant prostate cancer (mCRPC), a late-stage prostate cancer. The drug significantly improves patient outcomes: a Phase III trial showed an incremental overall survival benefit of 4.8 months compared to the placebo.

However, internal regulatory delays have mitigated patient impact in other countries. The Coalition estimates that 284,000 patient life-years could have been saved in Japan, the EU, Brazil, Canada, India, and China if Enzalutamide had been approved globally at the same time it was approved in the U.S.

"In China alone an estimated 500,000 patient life-years could be saved through harmonization of trial requirements that have delayed patient access to treatment," said Kevin Rudd, former Prime Minister of Australia, President and CEO of the Asia Society and Co-Chair of the Coalition.

Enzalutamide was not approved in China for mCRPC until November 2019, seven years after the U.S. approval. The lag was largely driven by a separate Asian multinational Phase III trial that Astellas conducted to meet China's specific regulatory requirements.

"This delay illustrates the importance for greater standardization and acceleration of global regulatory processes, even before new therapies are submitted for approval," said Rudd.

Encouragingly in recent years, China has been making significant strides to accelerate drug approvals and that in some cases the previous requirement for China-specific trials has been removed, as long as the foreign drug-maker conducts international, multicenter trials that include China as a site.

The coalition makes a series of recommendations aimed at building up international clinical trial standards

• Strengthen regulatory bandwidth: This is where internationalizing Project Orbis comes into play. In many countries, regulators have minimal capacity to evaluate and process drug approvals. This insufficient regulatory manpower and infrastructure results in longer waiting periods. Funding and training aimed at countries with less developed regulatory bodies can improve and elongate the lives of cancer patients around the world.
• Preliminarily define requirements for ethnicity-specific trials: Asia-Pacific (APAC) countries often require data from global trials with representation of the local patient population. This is less relevant for some drugs, but it is necessary for small molecule drugs as the dosing regimen varies by sensitivity. Define in advance which trials need this kind of consideration.
• Standardize manufacturing inspections: As part of the approval process, disseminate international guidelines that can be adopted by all countries so that country-specific requirements in this area don't cause unnecessary delays in approvals and treatment.
• Reform insurance coverage for life-prolonging treatments: Unlike in the U.S. where insurance coverage is directly tied to regulatory approval, coverage in many other countries is at the discretion of provincial payers (as is the case in Canada) and/or may only be covered by private insurance in the few years immediately following its approval (like in Brazil). Streamline these processes to expedite providing care to patients.
• Planning for approval in secondary markets. Investing in international market access before the U.S. authorities have approved a drug, understanding the country-specific regulatory requirements earlier, and strategically designing pivotal trials to facilitate faster international approvals.

About the Bloomberg New Economy International Cancer Coalition

In 2019, at the Bloomberg New Economy Forum in Beijing, a group of U.S-China experts convened to strategize areas where the two countries could collaborate. The expert group, co-led by Asia Society and Memorial Sloan Kettering Cancer Center, alongside Chinese and international bio-pharma companies and experts from the United States, Europe and other regions, put forward the idea of strengthening international clinical trial collaboration with the goal of accelerating development, access and approvals of cancer treatments that could save millions of lives. The Bloomberg New Economy International Cancer Coalition was born. A full list of members can be found here.

SOURCE Bloomberg Media