Can you quantify the problem?
Some say [the delay is] about 4.6 years—others say it's over six years. But what companies need to think about is, What is
the value lost to companies who don't have their drugs in the second-largest market of the world? Japan's a $60 billion market—so
it's huge. We also have to realize the patient side. Avastin, the cancer drug which was approved in the United States in 2004,
just was approved in Japan this year.
What's been the government's reaction?
It is allowing companies to use a lot more foreign data now. Iressa was one of the very first drugs to be approved using foreign
data, back in 2002. The Japanese government is also pushing for global studies and has opened up a separate window for people
to talk about that.
Pfizer's Detrusitol was approved last year with a global study. It used patients from Japan as well as from Taiwan and Korea
and showed how companies can supplement studies using data from outside the country.
What are global studies, and how do they work?
The idea behind global studies is to get things approved at the same time so Japanese patients don't have to wait.
The time to think about trying to leverage Japan as part of a global clinical strategy is no later than Phase I or maybe early
Phase II. And then the clinical team builds the protocols together. Instead of studying 600 patients in the United States,
you study 200 patients in America, 200 in Europe, and 200 in Japan simultaneously. It doesn't speed up FDA approval, but it
does speed up things in Japan because instead of waiting till the study finishes, you can conduct the clinical trials at the
same time. So the idea is to do Phase II and Phase III as part of a global study and file the New Drug Application simultaneously
in each region. That's the holy grail that everyone's shooting for.
Is there anything companies can do if a compound is further along in its clinical development?
Bridging is a concept that applies to drugs that are already in late-stage development and are undergoing clinical trials
outside of Japan. It means you already have the data, and now you have to somehow bridge it to Japan. Instead of redoing the
whole Phase III study, companies can bridge that data by doing a small study to just prove things are similar in the Japanese
and Caucasian populations. If the American, European, and Japanese protocols are similar, companies can leverage the international
data as part of the Japanese filing.
The International Conference of Harmonization (ICH) was the wind behind all this. It was built on the concept of safety, efficacy,
and quality. E5 was the guideline of ethnicity. It stated that researchers don't have to replicate studies as long as they
can prove that there's no intrinsic or extrinsic differences between the regions.
That's sometimes difficult to prove in practice, because you may have a great Phase III program done in the States, but how
do you make sure that the data really is applicable to Japanese people? It became pretty difficult. But it is possible, especially
in oncology. ICH has been a real godsend in that respect.
How many companies are currently bridging a study?
Most pharma companies are really thinking about it. The Western biotechs want to now get value from Japan quickly instead
of having to wait a long, long time. They want to see what Japan can bring.
Steve Engen is currently CEO of JapanBridge, which aims to gain rights to oncology drugs and market them in Japan. Previously, he was
president of Mundipharma in Japan and helped establish the company's headquarters there. Engen graduated from the University
of Utah in 1990 and received his MBA in 2000, from Temple University. He is a former chairman of Pharma Delegates Japan.