DM-1992 (Parkinson’s Disease Compound)

Parkinson's disease is a chronic, degenerative neurological disorder that affects nearly one million Americans, with significant prevalence growth expected over the next 25 years due to aging population demographics. Nearly 5 million worldwide are estimated to have Parkinson’s. While the average age at onset is 60, disease onset starts by age 40 in an estimated five to 10 percent of patients, and people as young as 30 can also be affected. Current therapies are effective in addressing only the mild/moderate motor symptoms of the disease and have significant long-term side effects. There are no drugs available that target the numerous non-motor aspects of the disease or that modify the underlying degenerative process.

Levodopa/carbidopa is the gold standard treatment of Parkinson’s Disease but currently has significant limitations with inconsistent efficacy (blood level fluctuations) and inconvenient dosing (4-6 times daily) since it is absorbed in the upper GI tract. Levodopa/Carbidopa is available as a generic (brand name Sinemet) and had $270 M in sales in the U.S. in 2006.

DM-1992, Depomed’s novel gastric retention formulation using its AcuForm™ technology, could optimize Levodopa/Carbidopa’s window of absorption and thus could smooth out blood level fluctuations and achieve more consistent efficacy, as well as reduce dosing frequency.

Development Status

On August 10, 2009, we announced that in our Phase 1 pharmacokinetic study in Parkinson’s patients, DM-1992 extended coverage above levodopa’s efficacious threshold and extended the time to peak levodopa concentration relative to currently available sustained release levodopa/carbidopa formulations.

One of Depomed’s formulations in the study extended the median time point at which levodopa blood levels exceeded the efficacious threshold of 300 ng/mL to approximately nine hours, compared to approximately seven hours for the generic version of Sinemet CR tested in the study. The time to median peak levodopa blood levels in the study was extended to four hours, compared to 2.8 hours for the comparator. DM-1992 was well tolerated in the study.

The Phase I trial in DM-1992 was a randomized, open-label crossover study that enrolled 18 patients with stable Parkinson’s disease at two leading neurology centers in Russia. The objective of the study was to compare the pharmacokinetics of two distinct formulations of DM-1992 and a generic version of Sinemet CR sustained-release Levodopa/Carbidopa, as well as the safety and tolerability of the formulations. Patients in the trial received a single dose of each of the three treatments being studied. A dose of the first treatment was administered at the beginning of the study, followed by a dose of a second treatment after 7 to 14 days, and a dose of the third treatment after another 7 to 14 days. Blood samples were drawn during the 24 hour period following administration of each treatment. Patients remained on any anti-Parkinson’s therapy other than Levodopa/Carbidopa during the trial.

In July 2008, The Michael J. Fox Foundation awarded Depomed a preclinical development grant to support the DM-1992 program.

Source: Medtrack