After years of deadlock, Japan’s doctors and pharmaceutical companies are preparing to begin clinical trials of a powerful blood clot-dissolving agent for treating brain infarction, the type of stroke that hit former Prime Minister Keizo Obuchi early this month, it was learned Wednesday.
Most Japanese doctors currently try to keep the patient’s brain alive by maintaining the functions of its undamaged part, rather than seeking to dissolve the blood clot.
By launching clinical trials of tissue plasminogen activator, or TPA, an agent designed to dissolve such blood clots, there is a greater chance that some patients will recover without suffering serious long-term disabilities.
Doctors say the drug could change the prevalent attitude in Japan that brain infarctions are untreatable, keeping thousands of patients out of nursing homes and reducing the nation’s nursing care burden.
Medical sources said two separate clinical trials are being planned to win governmental approval of TPA for emergency stroke treatment.
Yamanouchi Pharmaceutical Co. will test a version of the agent that they developed, while Kyowa Hakko Kogyo Co., Tanabe Seiyaku Co. and Mitsubishi-Tokyo Pharmaceuticals Inc. will jointly examine a drug produced under license from U.S. biotechnology giant Genentech Inc., according to the sources.
The companies will test the drugs, currently approved in Japan only for the treatment of heart attacks, to see if they are able to effectively — and more importantly, safely — dissolve clots in blood vessels supplying the brain.
After suffering a stroke on April 2, Obuchi remains in a coma at a Tokyo hospital. Obuchi’s doctors have not publicly discussed his condition, but some news reports have said that he was administered a less potent type of clot-dissolving agent.
Studies have shown that if a stroke sufferer is taken to a prepared hospital within three hours, TPA could possibly help the recovery by restoring blood flow to the brain — a critical factor in limiting damage.
Some doctors in Japan already use TPA as an effective treatment for strokes, although it is not covered by health insurance.
Media reports indicate that Obuchi’s doctors did not use TPA because it has not been approved as an anti-stroke drug.
After clinical tests begin, it will take between five and seven years for the Ministry of Health and Welfare to grant the drug approval, experts say. Doctors have asked the ministry for fast-track approval, saying the process could be streamlined, at least in the case of the Kyowa Hakko group, by using data collected in the United States. The United States approved the use of Genentech’s TPA for stroke therapy in 1996.
But ministry officials remain cautious, citing the potential risk of the drug causing fatal brain bleeding. The Kyowa Hakko group may not take part in the clinical study if it has to start from scratch, the sources said.
TPA actually came close to winning approval for stroke treatment in Japan in the mid-1990s after a clinical trial sponsored by Sumitomo Pharmaceuticals Co. confirmed the drug’s efficacy. But the company was forced to withdraw the product from the market in 1996 after losing a lawsuit filed by Genentech, which claimed Sumitomo infringed on its patent.
The suit was one of many battles over TPA fought by the world’s pharmaceutical companies, but the result was devastating for treatment of strokes in Japan, medical experts say. All the data collected in the world’s first clinical trial of TPA for strokes went down the drain.
Shortly thereafter, Genentech obtained approval from the U.S. government following a clinical study that found patients who were administered the drug within three hours of the onset of a brain infarction were up to 50 percent more likely than those not given the drug to have minimal or no disabilities after surviving a stroke.
Since then, TPA has been considered one of the most effective emergency treatments for the majority of stroke patients in the United States.