TOO MANY PROMISING drugs, too little time. It's a problem every company would love to have. But for discovery shops like Kyowa
Pharmaceutical, which rely on optimizing the value of compounds in development, managing the pipeline and patent life is a
After all, once a patent starts, it keeps on ticking no matter how fast the drug makes it to market. To beat the clock, this
US subsidiary of Tokyo-based Kyowa Hakko Kogyo is changing the way it conducts clinical trials. The company is making strides
to speed up initial safety and efficacy studies in order to get the earliest possible read on an investigational compound—and
then make the critical decision about whether or not to partner on the drug's development.
For Japanese companies just finding their feet in the United States, this decision is increasingly tricky. Kyowa's general
counsel and vice president of business development, Joseph Brindisi, discusses how the globalization strategy is changing
for Japanese pharmas as well as issues Kyowa faces as it prepares to file a New Drug Application with FDA for istradefylline,
its Parkinson's disease drug.
What are the biggest challenges in drug discovery and development?
A potential drug's value greatly increases—as does the interest from licensees—once there's evidence of safety and efficacy.
At the same time, the value goes down as its patent life shortens. If companies can get compounds to proof of concept—which
is Phase IIa—fast, it would enable them to choose which products to focus their own resources on and which products they should
Proof of concept is where a company shows that its drug meets efficacy endpoints. These trials are smaller than a Phase III
trial, and generally are not powered in a way to show a high rate of statistical significance. The drug may not even be tested
at the optimum dosing because the company hasn't yet done the dose-finding trials, either. But it's enough to show that the
product at this stage has some efficacy—and it's safe because it has completed Phase I trials.
How is Kyowa changing its R&D process?
We only run the trials that are necessary to establish sufficient safety, and then we progress to a small, controlled Phase
IIa clinical trial. Then to prove that the drug works, it's a matter of choosing one simple endpoint, rather than multiple
or more complicated endpoints that the company may need to show later on in order to market the drug. After it passes the
[Phase IIa] hurdle, companies can go back and conduct all of the other trials, like safety studies of longer exposure in animals
and other tests that supplement the safety package.
Growing competition is forcing Big Pharma to license compounds earlier. But ultimately will companies be satisfied taking
over preclinical and other early-stage programs?
If a company believes in its own development skills, it can enhance the quality and speed of a drug's development. It hopefully
can avoid any mistakes that a more inexperienced or a less resourced licensor might make while trying to develop the drug.
What will be interesting to watch is the tension between the licensors and the discoverers that have the vision to get to
market themselves. Can companies retain a right of copromotion with their partner that is going to develop these early-stage
products? Generally, if the licensees are going to put in the lion's share of the development investment, they are not going
to be too open to sharing in the marketing success later on.
The way Kyowa handles it is to bring about a balanced portfolio. We license some drugs at early stages, like the mitotic kinesin
Eg5 inhibitor we licensed to Eli Lilly. But then we retain the ability to develop other drugs, whether it's through Phase
IIa or all the way to NDA, like istradefylline.