New Alzheimer's drug yields modest memory improvements

SAN DIEGO – A new drug under investigation for Alzheimer’s disease showed modest improvements in patients’ episodic memory in a 12-week, phase IIa trial.*

The patients taking the drug, called ORM-12741, saw a 4% increase in their episodic memory performance while the placebo patients’ episodic memory performance declined 33%, Dr. Juha Rouru of Orion Pharmaceuticals, Turku, Finland, and his associates reported at the annual meeting of the American Academy of Neurology.

The proof-of-concept trial was a randomized, double-blind, placebo-controlled, multicenter trial that compared two different dosage levels of ORM-12741 against placebo in 100 patients. The patients all had moderate Alzheimer’s disease, with a score between 12 and 21 on the Mini Mental State Examination (MMSE). The patents also had behavioral symptoms with a Neuropsychiatric Inventory (NPI) score of 15 or greater.

The patients received either 30-60 mg or 100-300 mg of ORM-12741, or a matching placebo, twice a day for 12 weeks. The patients were already taking a cholinesterase inhibitor and were allowed to take memantine (Namenda) as well. Dr. Rouru said the ORM-12741 dosage flexibility was built into the study because previous human subjects receiving the drug did not have Alzheimer’s, so the flexibility allowed for safety adjustments if necessary.

The battery of tests to assess cognitive function in the study participants included the Quality of Episodic Memory (QEM), Quality of Working Memory (QWM), Quality of Memory (QM), Speed of Memory, and Power of Attention. The NPI was also used to assess other potential behavioral and psychological symptoms during the trial.

At follow-up, the patients receiving ORM-12741 scored a mean 4% higher on the QEM composite score, which combines both episodic and working memory. No significant difference was noted between dosage amounts. Patients in the placebo group scored a mean 33% lower on the QEM composite. In addition, the researchers reported a positive trend for both the QWM score and NPI total score in the low-dose group. No other significant differences were noted from the other assessments.

ORM-12741 differs from other Alzheimer’s drugs on the market, such as memantine or cholinesterase inhibitors, by acting on a completely different target, Dr. Rouru said. The drug targets a specific subtype of adrenergic receptors in the brain called alpha-2C.

"Quite little has been known about those receptors, and a big part of the work that has been done on them has been done in our company," Dr. Rouru said in an interview. "In animal models, we see very clearly they are involved in memory, but they are also fine tuners for many behavioral things. We have been able to demonstrate in animal models not only that drugs that target to these receptors improve memory, but that they have also beneficial effect on depressive and psychotic symptoms."

The different target offers clinical advantages in terms of treatment combinations, Dr. Rouru said. "The bottom line is that because the target is different, we can very easily use this drug in combination with other medications so that we are adding effect," he said.

Dr. Rouru said the drug was well tolerated among the participants and that adverse events were similar in both the intervention and placebo groups. It is too early to say what adverse events may have been attributed in the intervention group to ORM-12741, he said.

The most commonly reported adverse events were headache in 12% of placebo-treated patients and 5% of patients taking ORM-12741; urinary tract infection in 9% taking placebo and 9% taking ORM-12741; nausea in 9% receiving placebo and 5% receiving ORM-12741; vomiting in 3% taking placebo and 8% taking ORM-12741; diarrhea in 6% on placebo and 5% on ORM-12741; and irritability in 9% on placebo and 3% on ORM-12741.

Dr. Rouru said he is very pleased with the results of this trial, and he and his associates at Orion Pharma are now in the planning stages of the next clinical trial.

"It was very nice that the animal effect we saw, we saw in humans as well," Dr. Rouru said. "Also, the effect that we saw in humans was very clear, which was really encouraging for the future of this compound."

The study was funded by Orion Pharma. Two authors are Orion employees, and two authors work for World Wide Clinical Trials, the contract research organization involved in the trial. One author works for the company providing the computerized memory measurement system.

* This article was revised on 3/27/13.

SAN DIEGO – A new drug under investigation for Alzheimer’s disease showed modest improvements in patients’ episodic memory in a 12-week, phase IIa trial.*

The patients taking the drug, called ORM-12741, saw a 4% increase in their episodic memory performance while the placebo patients’ episodic memory performance declined 33%, Dr. Juha Rouru of Orion Pharmaceuticals, Turku, Finland, and his associates reported at the annual meeting of the American Academy of Neurology.

The proof-of-concept trial was a randomized, double-blind, placebo-controlled, multicenter trial that compared two different dosage levels of ORM-12741 against placebo in 100 patients. The patients all had moderate Alzheimer’s disease, with a score between 12 and 21 on the Mini Mental State Examination (MMSE). The patents also had behavioral symptoms with a Neuropsychiatric Inventory (NPI) score of 15 or greater.

The patients received either 30-60 mg or 100-300 mg of ORM-12741, or a matching placebo, twice a day for 12 weeks. The patients were already taking a cholinesterase inhibitor and were allowed to take memantine (Namenda) as well. Dr. Rouru said the ORM-12741 dosage flexibility was built into the study because previous human subjects receiving the drug did not have Alzheimer’s, so the flexibility allowed for safety adjustments if necessary.

The battery of tests to assess cognitive function in the study participants included the Quality of Episodic Memory (QEM), Quality of Working Memory (QWM), Quality of Memory (QM), Speed of Memory, and Power of Attention. The NPI was also used to assess other potential behavioral and psychological symptoms during the trial.

At follow-up, the patients receiving ORM-12741 scored a mean 4% higher on the QEM composite score, which combines both episodic and working memory. No significant difference was noted between dosage amounts. Patients in the placebo group scored a mean 33% lower on the QEM composite. In addition, the researchers reported a positive trend for both the QWM score and NPI total score in the low-dose group. No other significant differences were noted from the other assessments.

ORM-12741 differs from other Alzheimer’s drugs on the market, such as memantine or cholinesterase inhibitors, by acting on a completely different target, Dr. Rouru said. The drug targets a specific subtype of adrenergic receptors in the brain called alpha-2C.

"Quite little has been known about those receptors, and a big part of the work that has been done on them has been done in our company," Dr. Rouru said in an interview. "In animal models, we see very clearly they are involved in memory, but they are also fine tuners for many behavioral things. We have been able to demonstrate in animal models not only that drugs that target to these receptors improve memory, but that they have also beneficial effect on depressive and psychotic symptoms."

The different target offers clinical advantages in terms of treatment combinations, Dr. Rouru said. "The bottom line is that because the target is different, we can very easily use this drug in combination with other medications so that we are adding effect," he said.

Dr. Rouru said the drug was well tolerated among the participants and that adverse events were similar in both the intervention and placebo groups. It is too early to say what adverse events may have been attributed in the intervention group to ORM-12741, he said.

The most commonly reported adverse events were headache in 12% of placebo-treated patients and 5% of patients taking ORM-12741; urinary tract infection in 9% taking placebo and 9% taking ORM-12741; nausea in 9% receiving placebo and 5% receiving ORM-12741; vomiting in 3% taking placebo and 8% taking ORM-12741; diarrhea in 6% on placebo and 5% on ORM-12741; and irritability in 9% on placebo and 3% on ORM-12741.

Dr. Rouru said he is very pleased with the results of this trial, and he and his associates at Orion Pharma are now in the planning stages of the next clinical trial.

"It was very nice that the animal effect we saw, we saw in humans as well," Dr. Rouru said. "Also, the effect that we saw in humans was very clear, which was really encouraging for the future of this compound."

The study was funded by Orion Pharma. Two authors are Orion employees, and two authors work for World Wide Clinical Trials, the contract research organization involved in the trial. One author works for the company providing the computerized memory measurement system.

* This article was revised on 3/27/13.

SAN DIEGO – A new drug under investigation for Alzheimer’s disease showed modest improvements in patients’ episodic memory in a 12-week, phase IIa trial.*

The patients taking the drug, called ORM-12741, saw a 4% increase in their episodic memory performance while the placebo patients’ episodic memory performance declined 33%, Dr. Juha Rouru of Orion Pharmaceuticals, Turku, Finland, and his associates reported at the annual meeting of the American Academy of Neurology.

The proof-of-concept trial was a randomized, double-blind, placebo-controlled, multicenter trial that compared two different dosage levels of ORM-12741 against placebo in 100 patients. The patients all had moderate Alzheimer’s disease, with a score between 12 and 21 on the Mini Mental State Examination (MMSE). The patents also had behavioral symptoms with a Neuropsychiatric Inventory (NPI) score of 15 or greater.

The patients received either 30-60 mg or 100-300 mg of ORM-12741, or a matching placebo, twice a day for 12 weeks. The patients were already taking a cholinesterase inhibitor and were allowed to take memantine (Namenda) as well. Dr. Rouru said the ORM-12741 dosage flexibility was built into the study because previous human subjects receiving the drug did not have Alzheimer’s, so the flexibility allowed for safety adjustments if necessary.

The battery of tests to assess cognitive function in the study participants included the Quality of Episodic Memory (QEM), Quality of Working Memory (QWM), Quality of Memory (QM), Speed of Memory, and Power of Attention. The NPI was also used to assess other potential behavioral and psychological symptoms during the trial.

At follow-up, the patients receiving ORM-12741 scored a mean 4% higher on the QEM composite score, which combines both episodic and working memory. No significant difference was noted between dosage amounts. Patients in the placebo group scored a mean 33% lower on the QEM composite. In addition, the researchers reported a positive trend for both the QWM score and NPI total score in the low-dose group. No other significant differences were noted from the other assessments.

ORM-12741 differs from other Alzheimer’s drugs on the market, such as memantine or cholinesterase inhibitors, by acting on a completely different target, Dr. Rouru said. The drug targets a specific subtype of adrenergic receptors in the brain called alpha-2C.

"Quite little has been known about those receptors, and a big part of the work that has been done on them has been done in our company," Dr. Rouru said in an interview. "In animal models, we see very clearly they are involved in memory, but they are also fine tuners for many behavioral things. We have been able to demonstrate in animal models not only that drugs that target to these receptors improve memory, but that they have also beneficial effect on depressive and psychotic symptoms."

The different target offers clinical advantages in terms of treatment combinations, Dr. Rouru said. "The bottom line is that because the target is different, we can very easily use this drug in combination with other medications so that we are adding effect," he said.

Dr. Rouru said the drug was well tolerated among the participants and that adverse events were similar in both the intervention and placebo groups. It is too early to say what adverse events may have been attributed in the intervention group to ORM-12741, he said.

The most commonly reported adverse events were headache in 12% of placebo-treated patients and 5% of patients taking ORM-12741; urinary tract infection in 9% taking placebo and 9% taking ORM-12741; nausea in 9% receiving placebo and 5% receiving ORM-12741; vomiting in 3% taking placebo and 8% taking ORM-12741; diarrhea in 6% on placebo and 5% on ORM-12741; and irritability in 9% on placebo and 3% on ORM-12741.

Dr. Rouru said he is very pleased with the results of this trial, and he and his associates at Orion Pharma are now in the planning stages of the next clinical trial.

"It was very nice that the animal effect we saw, we saw in humans as well," Dr. Rouru said. "Also, the effect that we saw in humans was very clear, which was really encouraging for the future of this compound."

The study was funded by Orion Pharma. Two authors are Orion employees, and two authors work for World Wide Clinical Trials, the contract research organization involved in the trial. One author works for the company providing the computerized memory measurement system.

* This article was revised on 3/27/13.