Synthetic Biologics (NYSEMKT:SYN), formerly Adeona Pharmaceuticals, and its reaZin® prescription medical food for the management of Alzheimer's disease and mild cognitive impairment came full circle in early 2011. After some promising interim data in 2010, the final data was presented at the 63rd Annual Meeting of the American Academy of Neurology on April 14, 2011 in Honolulu, Hawaii. The data indicated that the clinical study met the primary outcome of increasing serum zinc and decreasing serum free copper. Per the presentation, secondary outcomes of mental status as measured by three standardized cognitive tests all favored the treatment group versus the placebo group. The secondary outcomes in this trial were the most important factors for the targeted indication, but the statement "favored the treatment group versus the placebo group" didn't give the full story with only a weak correlation in the biotech world. For this trial, a statistically significant (P < 0.05) was the sought after correlation, and none of the three measurements of mental status change met the desired endpoint. The secondary data were as follows:
- 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 (MMSE), an average net improvement of 0.19 points in favor of the treatment group versus placebo (p < 0.42)
Although the secondary data were somewhat disappointing, the company still indicated that it would stick with the indication and follow through with marketing the reaZin medical food for the dietary management of Alzheimer's disease and mild cognitive impairment. On April 20th they announced that they had executed an agreement with TG United, Inc. of Brooksville, Florida, to provide commercial-scale manufacturing capabilities for reaZin®. With the weaker secondary data set, Synthetic Biologics did find a sub-set of patients that were over 70 years old that mostly met the (P < 0.05) criteria of significance and intends to conduct another Alzheimer's disease clinical study to evaluate its proprietary zinc-based tablet in patients age 70 and over. The data for this subset were as follows:
- ADAS-Cog - Alzheimer's Disease Assessment Scale - Cognitive Subscale p-value: 0.037
- CDR-SOB - Clinical Dementia Rating Scale - Sum of Boxes p-value: 0.032
- MMSE - Mini Mental State Examination p-value: 0.067
The data from this subset was impressive enough that Synthetic Biologics began preparing a larger clinical study protocol to evaluate patients diagnosed with mild to moderate Alzheimer's disease who are age 70 and over. It was anticipated that the clinical study would enroll over 100 patients and that the evaluation period will be at least 12 months. They intend to develop reaZin® for this subset as a drug (as opposed to only making reaZin® available as a prescription medical food) and to conduct the study under an Investigational New Drug (NYSE:IND) application to be filed with the FDA.
The author applauds Synthetic Biologics' tenacity for the use of reaZin® in combating Alzheimer's disease and hopes for the best for the company and its target group. However, the 2011 year in review reported by Synthetic Biologics made absolutely no mention of any type of Alzheimer's trial. Their 3Q 2011 update, however, did note "Preparations are underway to conduct a larger clinical study of AEN-100 (our zinc-based drug candidate) under an IND application in patients with mild to moderate Alzheimer's disease who are age 70 and older. It is anticipated that the clinical study will enroll just over 100 patients and that the evaluation period will be at least 12 months."
Alzheimer's disease is relentless and is a sad disease to watch progress with little current hope of cure and only a little more hope of slowing its progression. There is another approach that Synthetic Biologics hasn't mentioned anywhere per the author's research that he hopes will be investigated. In the research that Synthetic Biologics and its team of experts that have been developing reaZin® have undertaken, much work has been done to cure and slow the progression of Alzheimer's disease and mild cognitive impairment. They have accomplished much for the purpose of their own marketing of reaZin® and for the education they've provided to the medical community and patients in general. However, in many studies the beta amyloid plaque and the damage its buildup causes to the neurons in the brain is the central focus of attacking the disease. Some of this damage, even if the plaque if removed or redissolved and removed by the patient's body, may be irreparable. Not stating that there is no cure after a certain level of progression but rather the author hopes that Synthetic Biologics, with the approach it has chosen to undertake in attacking the disease, may need to refine its approach with an additional means of trying to prevent rather than only trying to cure the disease.
The author's proposal to Synthetic Biologics is that it considers a trial on patients with a predisposition to developing the disease based on genetics or based on very early detection of the disease. Particularly exciting is a 2010 article in the New York Times about a study led by Belgian and US researchers on the very early detection of Alzheimer's. The study found certain biomarkers in spinal fluid that provided a "signature" that was able to identify 94 percent of a group of patients that had developed Alzheimer's whose disease had been confirmed by autopsies. The study was also able to identify every patient (patient size not disclosed) with mild cognitive impairment who would go on to develop Alzheimer's disease within five years. This type of early detection or even prediction, if legitimized, would be a radical development in the treatment and prevention of Alzheimer's. It would enable companies with novel preventatives or cures to have a new approach and new group of individuals to include in their future trials. This could be key for a company taking an approach, like Synthetic Biologics, that does not focus primarily on the beta amyloid plaque removal. According to the Fisher Center for Alzheimer's Research Foundation website, there are over 100 clinical trials being conducted on Alzheimer's and dementia. If Synthetic Biologics or one of these other biotechs, pharmaceuticals or universities has the silver bullet already in its arsenal, a means of predicting Alzheimer's disease at its very earliest stages may be the key target the silver bullet should be aimed at. Take heed, Synthetic Biologics and its investors, there are millions of patients and families watching and waiting.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.