In a Nov. 27, 2017 research note, Fein reported the key themes from the 10th Clinical Trials on Alzheimer's Disease (CTAD) meeting.
Target population shift
A major change is taking place within the field of developing therapeutics to treat Alzheimer's patients. Efforts in this regard are increasingly focusing on the initial and early disease stages and on the "preclinical or mild cognitive impairment patient population," rather than on the standard concentrations of symptomatic patients and late-stage disease, Fein noted.
Driving this shift, Fein said, are:
1. The knowledge gained to date from clinical trials, especially ones involving amyloid beta
2. A better understanding of Alzheimer's disease progression as a continuum
3. The belief that the high failure rate in Alzheimer's trials has been due, at least in part, to intervention being too late.
Despite these arguments for early intervention, the potential success of that approach remains unknown. "Is early targeting the solution for treating Alzheimer's disease effectively, or should we focus on innovative approaches and bringing more efficacious drugs into the pipeline?" Fein queried.
Also, targeting earlier-stage Alzheimer's disease patients is challenging, which has likely been the primary obstacle to previous studies being conducted in this group.
These trials require large numbers of participants, up to about 2,000. They also have long durations, typically spanning more than two years. This is "a deterrent, considering that the current symptomatic drugs can offer benefits within six months, and the safety profile of new therapies is not fully delineated," Fein wrote.
The need for large cohorts and long durations is because cognitive function in early-stage patients declines slowly. Identifying and locating such individuals becomes "not only an issue of cost, but also a question of practicality," explained Fein.
The industry is demonstrating "increasing interest and research effort focusing on resolving the challenges" and is "making significant strides in advancing early intervention trials," Fein concluded. However, "there still remains plenty to learn. Progress is being made, but there is still a long way to go."
Amyloid beta news
Another major takeaway from the CTAD is that several late-stage trials have shown results from reducing amyloid beta deposition. "The recent data presented at the meeting suggested that other than the IgG4 backbone, the lack of binding to vascular amyloid beta may contribute to its unique safety profile," Fein said.
For one, Roche Holding AG's (RHHBY:OTCQX) gantenerumab, an anti-amyloid antibody, at greater than or equal to six doses of 900–1,200 milligrams "significantly reduced amyloid beta deposition as measured by amyloid PET scan" at nine to 12 months, indicated Fein. "Roche has demonstrated in its open-label extension studies that using four times or even five times higher doses could reduce amyloid beta deposition to a potentially therapeutic level," he added.
For another, Biogen Inc.'s (BIIB:NASDAQ) aducanumab, also an anti-amyloid antibody, showed "a dose-dependent reduction of amyloid beta plaques" in the Phase 1b PRIME long-term extension study," Fein noted. Interim data from this trial "seem to be incrementally supportive of early intervention."
Role of genetic info
The industry also is developing genetic tests and biomarkers to help to identify risk factors and better define Alzheimer's patients, said Fein. At the conference, Dr. John Hardy, an Alzheimer's disease genetics expert, indicated that a polygenic risk score could help predict one's likelihood to develop the disease. Fein added, "The genetic findings in late onset Alzheimer's disease show that many of the risk loci are microglial expressed and/or responsive to amyloid deposition, many of which are related to membrane metabolism."
Other areas of ongoing Alzheimer's research that may hold potential, Fein reported, include:
1. Exploring synaptic and network dysfunction.
2. Further studying GSK2606414, a PERK inhibitor that decreased taopathy in mice with dementia.<
3. Repurposing drugs, such as trazodone and dibenzoylmethane, which showed neuroprotectivity in mice with prion disease.
4. Investigating modulating brain oscillation.
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Disclosures from H. C. Wainwright & Co., Industry Update, "Focusing on Early Intervention: New Learnings and Key
Insights From the 10th Clinical Trials on Alzheimer’s Disease," Nov. 27, 2017
I, Andrew S. Fein and Li Wang Watsek , certify that 1) all of the views expressed in this report accurately reflect my personal
views about any and all subject securities or issuers discussed; and 2) no part of my compensation was, is, or will be directly
or indirectly related to the specific recommendation or views expressed in this research report; and 3) neither myself nor any
members of my household is an officer, director or advisory board member of these companies.
None of the research analysts or the research analyst’s household has a financial interest in the securities of Biogen, Inc
(including, without limitation, any option, right, warrant, future, long or short position).
As of October 31, 2017 neither the Firm nor its affiliates beneficially own 1% or more of any class of common equity securities
of Biogen, Inc.
Neither the research analyst nor the Firm has any material conflict of interest in of which the research analyst knows or has
reason to know at the time of publication of this research report.
The research analyst principally responsible for preparation of the report does not receive compensation that is based upon any
specific investment banking services or transaction but is compensated based on factors including total revenue and profitability
of the Firm, a substantial portion of which is derived from investment banking services.
The Firm or its affiliates did not receive compensation from Biogen, Inc for investment banking services within twelve months
before, but will seek compensation from the companies mentioned in this report for investment banking services within three
months following publication of the research report.
The Firm does not make a market in Biogen, Inc as of the date of this research report.