Treatments From China: What Data Are Needed and Who Decides?

David J. Kerr, CBE, MD, DSc


October 12, 2022

This transcript has been edited for clarity.

I'm David Kerr, professor of cancer medicine at University of Oxford.

I've been really interested in the tit-for-tat argument that's going on between the FDA and other commentators and its Chinese regulatory equivalent. This all circles around the recent biologics license application from a company that was marketing an immune checkpoint inhibitor called sintilimab.

They've done a trial in non–small cell lung cancer comparing sintilimab vs chemotherapy. The trial outcome was positive, but it was done completely within China.

The regulatory package was put forward to the FDA, but it was turned down. There are a number of different factors around endpoints, standards of care, insufficient pharmacokinetic data, and competitiveness. Do we need any more immune checkpoint inhibitors, given the relatively large number that have been approved already?

Perhaps the most telling point was that the study was conducted only in Chinese patients. This led to an interesting discussion among US and Chinese key opinion leaders and the regulatory authorities.

It does represent a really interesting challenge because until relatively recent times, China was the recipient of innovative Western medicines. The Chinese authorities, depending on the drug, the size of the benefit, and so on, might have required a bridging study or some form of crossover.

If they felt that the disease was etiologically different in China, they may require a separate, additional randomized trial to demonstrate the new benefits. That was the case with a drug that was marketed for treatment of hepatocellular cancer, which one could argue is manifestly different in Eastern Asia than it is in the West.

In these days of globalization, we're used to multicenter trials in which big pharma recruit patients from around the world and then do some subgroup analysis to see if the hazard ratios are the same and are independent of ethnicity.

Of course, that can generate some really interesting hypotheses, as was the case in terms of endothelial growth factor receptor (EGFR) inhibitors for the treatment of lung cancer that spawned studies looking at EGFR mutants that are responsive to these drugs and were more common in Eastern Asian populations.

Back to the immune checkpoint inhibitors. There are no data that I know of that suggest any major differences in ethnic handling of these drugs in terms of the pharmacokinetics. The response rates in drugs that have moved from West to East seem very similar. The distribution and kinetics of the handling of antibodies is relatively straightforward and doesn't seem to vary in terms of ethnicity.

There's a very interesting debate to be had about it because there are now more innovative medicines in the pipeline from China, which is fantastic. Building on some of the truly innovative sciences coming from there, I think we'll see more drugs coming from East to West.

Clearly, we need to consider very carefully what trial data we require. Would we take a predominantly Chinese study and then look at a small pharmacokinetic study or a crossover study in a relatively small population of Caucasian patients, depending on the etiology of the disease? Would we require additional randomized trials to be undertaken in a Caucasian population for the Chinese medicine coming over?

We need the regulatory authorities to get together. As a community of oncologists, we are very happy to collaborate. We're very happy to have trials that draw participants from around the world in sufficient number for us to look for subtle but sometimes important differences in patterns of toxicity, response rates, and so on. Having globalized cancer trials may well be the answer.

I think we need to see a greater degree of consistency coming from the regulatory authorities around the world as to what information we really require, and above all else, if we have a set of rules, to apply these consistently across any of the new drugs that are coming in.

Have a look at the publication in the Journal of Thoracic Oncology. See what you think. Are we being fair? Is there an ethnic bias creeping in? Is it scientifically sound? I'd be interested in your viewpoint.

For the time being, Medscapers, thanks for listening. Over and out, and ahoy. Thank you.

David J. Kerr, CBE, MD, DSc, is a professor of cancer medicine at the University of Oxford. He is recognized internationally for his work in the research and treatment of colorectal cancer and has founded three university spin-out companies: COBRA Therapeutics, Celleron Therapeutics, and Oxford Cancer Biomarkers. In 2002, he was appointed Commander of the British Empire by Queen Elizabeth II.

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