Alzheimer's patients, particularly those in the later stages of the disease, might have newfound hope with a drug that could keep them out of nursing homes and enable them to function in society longer.
Neurobiological Technologies Inc. (NTI) received a unanimous, favorable FDA panel recommendation on Wednesday afternoon for the approval of memantine, which would be marketed under the trade name Namenda by New York-based Forest Laboratories if final approval is granted later this year.
The Peripheral and Central Nervous System Drugs Advisory Committee unanimously voted for the drug's safety and effectiveness. The FDA is expected to announce Namenda's fate by Oct. 19.
"I think that [Wednesday's] unanimous panel approval was a big step and pretty much ensures that memantine will gain approval," said Sherry Grisewood, analyst with J.M. Dutton & Associates in New York. "It's a big step for Alzheimer's patients because the others approved are for the mild form of the disease, and this is the first drug that operates by a different pathway."
Currently, four drugs are marketed in the U.S. for Alzheimer's disease: Pfizer Inc.'s Aricept, Novartis AG's Exelon, First Horizon Pharmaceutical Corp.'s Cognex and Shire Pharmaceuticals Group plc's Reminyl. However, all four of those are indicated for mild to moderate Alzheimer's disease, whereas Namenda would target the most severe stage of the disease.
"All diseases are terrible, but Alzheimer's has to be one of the worst diseases you can get," said Ronny Kraft, company spokesman for Richmond, Calif.-based NTI. "If you get cancer, either it's treatable or not treatable and you win or lose the battle. With Alzheimer's, you can have cognitive and neurological impairment, but physiologically be doing great."
Kraft said that clinical results have shown that Namenda will extend the time a person has control over faculties such as going to the bathroom and getting dressed. "They're going to stay out of a nursing home longer," he told BioWorld Today, "and if they do go into a nursing home, it's going to be a mild care facility."
The four drugs approved in the U.S. all work by preventing the breakdown of acetylcholine, while memantine works by blocking abnormal effects of glutamate. Acetylcholine and glutamate each play a role in learning and memory. Memantine is thought to selectively block the excitotoxic effects associated with abnormal transmission of glutamate, but it also allows for the physiological transmission associated with normal cell functioning.
The FDA panel looked at data from Phase III trials, one of which included 252 patients and another of which enrolled 401 patients. The drug was shown to be safe and well tolerated, with the most common adverse events being dizziness, headaches, fatigue and somnolence.
Memantine is currently marketed in Europe by Lundbeck A/S under the name Ebixa, and by Merz Pharmaceuticals GmbH under the name Axura. It has been sold since 1982 in Germany. If approved in the U.S., Kraft said it could be on the market as early as the first quarter of next year.
Wall Street sales estimates for Namenda are around $700 million to $1 billion in the two to three years following its launch.
"By and large, it's going to follow the same class as Exelon and Aricept because the side effects are very benign," Grisewood told BioWorld Today.
Kraft said Pfizer's drug Aricept, the market leader, does about $1.2 billion annually. "[Namenda] is superior on the efficacy side and superior on the side-effect side," he said.
And with Memantine's history in Germany, the side-effect profile is well known. "You don't have a lot of those other issues that go along with a new chemical entity," Grisewood said.
Memantine was synthesized in the late 1970s by privately held Merz, which later got the drug approved for Parkinson's disease believing it was a dopamine agonist. For a number of years, the company noticed the patients were doing better cognitively, but the drug seemed to have no effect on physical shaking. Scientists eventually discovered that memantine was an N-methyl-D-aspartate receptor antagonist, causing them to shift gears and focus on Alzheimer's disease. Once the composition of matter patent expired, Merz took out a use patent and started development in the early 1990s. NTI licensed the use patent from Children's Hospital at Harvard University in the early 1990s, and developed it for diabetic neuropathy and age-related dementia. It later formed an agreement with Merz, allowing the German company to take a piece of the diabetic neuropathy indication, giving NTI rights to memantine for Alzheimer's disease in the U.S. and some parts of Europe and the rest of the world. Merz holds the rights for memantine for Alzheimer's disease in most of Europe, specifically the German-speaking countries, Kraft said.
In the U.S., NTI conducted a Phase III trial of memantine in diabetic neuropathy, with good results. However, Forest Laboratories conducted a larger-scale Phase III trial that failed. Kraft said Forest would need to make a decision as to whether it will do another trial.
If Namenda is approved, NTI will receive a performance fee from Forest through Merz. It also is entitled to single-digit royalties from sales in the U.S.
About 4.5 million Americans have Alzheimer's disease, the most common type of dementia. That number is expected to increase to 5.5 million by 2010, according to the Alzheimer's Association. An early stage symptom of the disease is forgetfulness, while people with the later, more-severe stages of the disease need constant help with bathing, eating and other daily tasks.
NTI and Forest originally filed an NDA in August 2002, but later withdrew it in order to correct structural and formatting problems identified by the FDA. It resubmitted the NDA in December 2002.
NTI's stock (NASDAQ:NTII) fell 49 cents Thursday to close at $6.08.