Advancing its lead therapeutic candidate into pivotal development, Myriad Genetics Inc. began enrolling patients in a Phase III trial of Flurizan (MPC-7869) for Alzheimer's disease.
The 750-patient study is designed to determine the product's ability to alter the course of cognitive decline and behavioral change in those with mild to moderate forms of the disease. Its primary efficacy endpoints will measure changes in cognitive function, as assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale test, and changes in daily living activities.
"It is our first drug to reach Phase III, which is a significant milestone for the company," William Hockett, Myriad's vice president of corporate communications, told BioWorld Today. "Flurizan is a drug for a large indication with a significant unmet medical need, and eventual FDA approval of Flurizan would be a very significant event for the company and potentially transform it from a biotechnology company to a biopharmaceutical company."
The drug operates as a lowering agent of amyloid beta 42, a toxic peptide believed to be a chief culprit in causing the disease. It also has been shown to modulate gamma-secretase, and the Salt Lake City-based company said such mechanisms could change the rate of decline in Alzheimer's patients.
"Flurizan, in earlier testing, has been shown to lower levels through a mechanism that alters the amyloid that's produced from this toxic version to other versions that are not toxic," Hockett said, adding that the drug remains in Phase II testing in a 210-patient study. All those patients, who have mild to moderate Alzheimer's disease, have been on the drug for more than nine months. The trial is expected to conclude in March, with topline results likely coming in May.
To further evaluate the drug's ability to function as described, the company is conducting the Phase III study, a double-blinded, placebo-controlled trial at about 100 U.S. sites. Patients will be randomized into one of three arms: twice-daily doses of 400-mg Flurizan, 800-mg Flurizan or placebo for 12 months. The Phase II study, which is being conducted in the UK and Canada, follows the same design.
Results from both trials could help differentiate drugs already sold for Alzheimer's from Myriad's product.
"Nothing currently on the market affects the underlying mechanism in Alzheimer's disease," Hockett said. "Drugs on the market now are mostly acetylcholinesterase inhibitors that improve cognition for a period of time, but the underlying course of the disease continues, and fairly soon the individuals are on the same slope of decline that they were on prior to taking a drug."
Products that work by preventing the breakdown of acetylcholine include Aricept (donepezil HCL, from Pfizer Inc.), Exelon (rivastigmine tartrate, from Novartis AG), Cognex (tacrine HCL, from First Horizon Pharmaceutical Corp.) and Reminyl (galantamine hydrobromide, from Shire Pharmaceuticals Group plc). A more recently approved drug, Namenda (memantine HCL), is marketed in the U.S. by Forest Laboratories Inc., of New York. Hockett said patients in the Phase III study would be allowed to continue existing therapy with Namenda; many Phase II patients have been on acetylcholine inhibitors in addition to Flurizan.
With positive Phase III results, Myriad could file a new drug application by the end of 2006.
"We believe that the first-year sales potential of a drug that could slow the cognitive decline in Alzheimer's disease is in the order of hundreds of millions of dollars," Hockett said. "By accelerating the Flurizan program by at least nine months, there's a very favorable risk-reward ratio to Myriad and its investors."
In addition to Alzheimer's, the drug has been tested for use in prostate cancer patients. More than three years ago, the company said it would begin a multicenter, double-blinded, placebo-controlled trial for that indication. A Phase IIb trial involving about 260 patients, it could be the basis of a new drug application for prostate cancer should results prove positive and assuming the FDA agrees that the data support a filing. The study will continue for another year. (See BioWorld Today, Dec. 21, 2001.)
A dual mechanism drug, Flurizan is designed to impact prostate cancer through its workings in the nuclear factor kappa B pathway.
Myriad owns all rights to the drug and is considering marketing partnerships for the Alzheimer's indication in the U.S. and overseas, but expects to independently commercialize it for cancer.
Beyond its news on Flurizan, the company recently filed investigational new drug applications to begin Phase I trials of MPC-2130 and MPC-6827, both of which are being developed to induce apoptosis in cancer cells.
On Wednesday, Myriad's shares (NASDAQ:MYGN) gained $3.02, or 13.7 percent, to close at $24.95.