Regulatory Coordination For Cancer Clinical Trials Can Save 1.5 Million Lives Annually

Millions of lives in Japan, the EU, Brazil, Canada, India, and China could be saved if patients were able to be treated with pembrolizumab and enzalutamide, a new study found.

NEW YORK, Oct 18 – A new study has found that at least 1.5 million deaths from cancer, representing 20 per cent of global cancer deaths, could be avoided each year if international regulations around patient trials were more standardised and people placed on life-saving treatments such as pembrolizumab and enzalutamide.

The study by members of the Bloomberg New Economy International Cancer Coalition was published in the Harvard Business Review yesterday ahead of the World Cancer Congress convened by the Union for International Cancer Control (UICC) taking place in Geneva, Switzerland this week. 

It analysed how the simultaneous international regulatory approvals of the two drugs, pembrolizumab and enzalutamide, would have benefited patients around the world. 

According to the coalition, despite the United States Food and Drug Administration’s (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. 

“In China alone, an estimated 500,000 patient life-years could be saved through harmonisation of trial requirements that have delayed patient access to treatment,” said Kevin Rudd, former Prime Minister of Australia, and president and CEO of the Asia Society and co-chair of the Bloomberg New Economy International Cancer Coalition.

Pembrolizumab is used to treat patients with metastatic non-small cell lung cancer (NSCLC), the most common type of lung cancer, whose tumours 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 Three trial found that for patients with tumours that had high expression of PD-L1 (about 30 per cent 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 US. Despite the significant patient impact, the drug experienced approval delays outside the US – 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 six countries and regions with the highest tumour burden – namely, 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 US.

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. A Phase Three 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 US.

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

“This delay illustrates the importance of greater standardisation 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 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. 

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 in 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 drug approval and prolong the lives of those who are in critical need of treatment,” said UICC past president Mary Gospodarowicz, a member of the coalition who is a professor of radiation oncology at the University of Toronto and former medical director at the Princess Margaret Cancer Centre in Toronto, Canada.

Michael R. Bloomberg, founder of Bloomberg LP and Bloomberg Philanthropies, said cancer treatments should not be held up at such high costs given rapid advancements made in the field. “The more that countries come together and collaborate, the faster that patients around the world can access life-saving care.”

The Bloomberg New Economy International Cancer Coalition was launched last year to promote 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 centres and universities worldwide. 

Pharmaceutical company AstraZeneca plc has just been announced as the latest member to join the group.

The coalition has made a series of recommendations aimed at building up international clinical trial standards.

Strengthen regulatory bandwidth: This is where internationalising 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 countries often require data from global trials with a 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.

Standardise 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 US 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 US authorities have approved a drug, understanding the country-specific regulatory requirements earlier, and strategically designing pivotal trials to facilitate faster international approvals.

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