Merck licenses stroke drug from Ono
treatment of stroke, developed by Japan's Ono Pharmaceutical, in
the hope of developing what would be only the second drug to treat
Despite the high incidence of stroke - it affects anything between 19 and 70 people per 1,000 in Europe, depending on age - medical science has been unable to come up with an effective treatment.
Stroke is the third leading cause of death in North America and Western Europe and the most common cause of adult long-term disability in the US, but there is only one stroke therapy approved for marketing. This is Genentech's tissue plasminogen activator Activase (alteplase or rt-PA), a thrombolytic that targets the offending blood clot within the brain and marked a revolution in stroke management.
However the very short window of opportunity for administering rt-PA to stroke victims limits the usefulness of this treatment. It acts by restoring blood flow to the ischaemic region, but should only be initiated within three hours of the onset of stroke symptoms and after exclusion of intracranial haemorrhage. Only about 2 per cent of those who suffer a stroke reach a hospital in time and qualify for treatment with t-PA, underscoring the need for novel new treatments for stroke.
Merck has taken out a license to develop ONO-2506 ((R)-(-)-2-propyloctanoic acid), a novel intravenous compound currently in Phase II development.
ONO-2506 has a novel mechanism of action and is believed to inhibit expansion of cerebral infarction by modulating the function of astrocytes, a type of glial cell in the brain. Early studies suggest that ONO-2506 may exhibit a neuroprotective effect by preventing irreversible injury to neurons in the brain.
ONO-2506 is being studied to determine if it has a longer therapeutic time window of administration and a lower risk of bleeding than t-PA, as well as to learn if it may have neuroprotective benefits that could reduce the cerebral injury from stroke.
During the 1990s, a number of potential neuroprotectant drugs that block glutamate excitotoxicity were tested. In animal models of acute ischemic stroke, many of these drugs were effective in mitigating further damage caused by the stroke cascade when given within 30 minutes, and occasionally up to two hours, after stroke. However, when subsequently tested in human patients up to 12 hours after stroke, they did not demonstrate statistically significant efficacy.
Under the terms of the agreement, Ono will receive an initial payment and milestone payments in addition to royalties on net sales. Additional financial terms were not disclosed.
In addition, Ono will receive exclusive rights in Japan to develop and market EMEND (aprepitant), Merck's drug for use in combination with other antiemetic agents for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including cisplatin. Ono also receives rights in Japan to co-market a second brand of MK-431, Merck's investigational oral compound for the treatment of diabetes, under a yet to be determined trademark.
Ono retains rights to the injectable formulation of ONO-2506 in Japan, Korea and Taiwan. Ono also retains worldwide rights to other formulations of ONO-2506.
Datamonitor notes that the potential market for an efficacious and safe stroke drug is enormous, given the high incidence of the disorder worldwide. Assuming a relatively conservative cost of treatment of $1,000, for example, the market is potentially worth half a billion dollars annually in the US alone.