By M.E. Garza
Adeona Pharmaceuticals (AEN), a company we first told you about in December, announced today top-line results from its clinical study evaluating reaZin for the dietary management of Alzheimer's disease and mild cognitive impairment. The clinical study met the primary outcome of increasing serum zinc and decreasing serum free copper. In addition, secondary outcomes of mental status as measured by three standardized cognitive tests all favored the treatment group versus the placebo group.
You may recall that Adeona Pharmaceuticals is developing innovative medicines for the treatment of serious Central Nervous System diseases. Their primary strategy is to license product candidates that have demonstrated a certain level of clinical efficacy and develop them to a stage that results in a significant commercial collaboration – basically this means they develop their product candidates to attract large pharmaceutical partners with deep pockets. As we reported in December, AEN has demonstrated success with corporate partnering, they have started actively promoting the progress and potential of the clinical programs. They have expanded current revenue potential with their own clinical lab and we see them diligently trying to preserve cash. With several potential product candidates in the pipeline – it not only seems likely they should attract additional partners, they are actively working on it.
Their latest clinical study data was presented yesterday at the Annual Meeting of the American Academy of Neurology in Honolulu, Hawaii by Diana Pollock, M.D., Lead Principal Investigator of the study at Morton Plant Neuroscience Institute on the campus of Morton Plant Hospital.
Two scientific observations support Adeona's hypothesis that correcting zinc and free copper abnormalities could benefit AD patients as measured by cognitive scores. The first observation is derived from studies conducted by Dr. Squitti and her group that have shown the following: 1) AD patients have elevated levels of serum free copper (2) and 2) the elevated levels of free copper correlate with lower cognitive function (3) and, over time, a decline in cognitive function (4). The second observation is the finding that AD patients are zinc deficient compared to age-matched control patients (5). These findings suggest that elevated free copper is toxic to the brain of AD patients. Therefore, based on these scientific observations, Adeona's therapeutic strategy for the reaZin clinical study is to correct zinc deficiency and to lower serum free copper in AD patients. Based on findings in Wilson's disease (a disease characterized by toxic levels of free copper), oral zinc is known to lower serum free copper.
The prospective, randomized, double-blind, placebo-controlled clinical study represents the first controlled clinical study evaluating the safety and efficacy of a zinc and cysteine-based therapy (reaZin) for Alzheimer's disease. Study subjects were randomized into the active treatment group or the placebo group and were assessed at baseline, 3 months and 6 months. Primary outcome measures include serum zinc and serum free copper. Secondary outcomes include cognitive measures using ADAS-Cog, CDR-SOB and MMSE.
"We are highly encouraged by the results from this clinical study, especially achieving the primary outcome with the statistically significant change in the free copper to zinc ratio in the treatment group over the placebo group," stated George J. Brewer, M.D., Adeona's Senior Vice President of Research & Development. "Also, of ultimate importance with respect to a potential treatment for Alzheimer's disease patients, the composite score supports cognitive benefit in the treatment group versus the placebo group."
Dr. Pollock also commented on the clinical study, "In my clinical experience, this zinc therapy appears to have been extremely well tolerated and may represent a new mechanism of action to address the cognitive deficits in Alzheimer's patients. This potential treatment deserves further study in larger clinical trials."
The poster titled "Clinical Trial Results of the First Controlled Clinical Trial of Zinc-Based Therapy for Alzheimer's Disease and Mild Cognitive Impairment" included findings from 42 of 57 subjects evaluable at the end of the study. The results are as follows:
- The treatment group showed significant reductions in serum free copper levels and elevations in serum zinc levels over the placebo group, resulting in a highly statistically significant change in the free copper to zinc ratio (-20.8%), the primary outcome of the clinical study (p < 0.0006).
- An average net decrease in serum free copper of -6.5 microg/dL for the treatment group versus placebo group.
- An average net increase in serum zinc of 64.6 microg/dL for the treatment group versus the placebo group.
- Comparisons of the average changes in cognitive scores at baseline and 6 months are presented below. Although the individual p-values of the cognitive scores did not achieve statistical significance (p < 0.05), all three of these cognitive measures favored the treatment group versus the placebo group.
- Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), an average net improvement of 0.41 points in favor of the treatment group versus placebo (p < 0.36)
- Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB), an average net improvement of 0.38 points in favor of the treatment group versus placebo (p < 0.10)
- Mini Mental State Examination, an average net improvement of 0.19 points in favor of the treatment group versus placebo (p < 0.42)
- The Estimated Generalized Least Square method(1) was used to calculate a composite cognition score combining each of the secondary cognitive measures (ADAS-Cog, CDR-SOB and MMSE) at baseline and 6 months. The composite cognitive score approached statistical significance, indicating a strong trend toward cognitive benefit favoring the treatment group (p < 0.15).
- Results reported from Part 2 of this clinical study demonstrated that reaZin was safe and well tolerated by subjects in the treatment group and dropouts were equivalent across the treatment and placebo groups. These results confirm the previously reported results from Part 1 of the clinical study (April 14, 2010) that demonstrated reaZin was well tolerated and superior to Galzin®, an FDA-approved zinc preparation.
A copy of the poster presented at the AAN meeting is available here.
Adeona will hold a conference call/audio webcast to discuss the results from the clinical study evaluating reaZin for the dietary management of Alzheimer's disease and mild cognitive impairment on Friday, April 15, 2011, at 2:00 p.m. (EDT). James S. Kuo, M.D., M.B.A., Adeona's Chief Executive Officer and Diana Pollock, M.D., Lead Principal Investigator of the study at Morton Plant Neuroscience Institute on the campus of Morton Plant Hospital, will host the call. Interested parties should call toll free 1-800-860-2442 (U.S.) or 1-866-605-3852 (Canada), or from outside North America +1 412-858-4600, fifteen minutes before the start of the call to register and identify themselves as registrants of the Adeona Conference Call. Any registered caller on the toll free line may ask to be placed in the queue for the Question & Answer session. The call will be simulcast on the web. If you are unable to participate during the live call, the webcast will be available for replay at www.adeonapharma.com for 30 days after the call.