Conference Coverage
WASHINGTON, DC—Fifty-seven new drugs for Alzheimer’s disease currently are in phase II studies, according to an analysis conducted by Researchers Against Alzheimer’s (RA2). Nearly twice as many mechanisms of action are being tested in phase II than in phase III clinical trials, the group said. This diverse pipeline could provide physicians, persons with Alzheimer’s disease, and their loved ones with new ways to combat the disease in the future.
Advancements in Alzheimer’s Disease Drug Development
As the development of these compounds progresses, and the science of Alzheimer’s disease drug development advances, policy makers, clinical researchers, drug developers, and other Alzheimer’s disease drug partners need to create new clinical trial infrastructure and designs that allow for rapid recruitment and testing, consistent high-quality data, and prompt data disclosure, said RA2.
“These potentially game-changing drugs on the horizon may make Alzheimer’s [disease] a manageable disease,” said George Vradenburg, Cofounder and Chair of USAgainstAlzheimer’s, a group that advocates for a cure for Alzheimer’s disease. “To assure our best shot at success, we must ensure that the necessary investments are being made to build a 21st-century infrastructure to test their effectiveness and an innovation-friendly path to market [for] those in need,” he said.
George Vradenburg
The first RA2 pipeline analysis released in March found 17 Alzheimer’s disease drugs in phase III clinical trials planned to launch in the next five years. However, since the initial phase III pipeline report was issued, several Alzheimer’s disease drug candidates have moved from phase II to phase III clinical trials. According to the most recent analysis, 23 Alzheimer’s disease drugs are in phase III clinical trials. In all, 19 drugs could reach the market in the next five years, according to RA2.
Researchers and pharmaceutical companies are increasingly focusing on disease-modifying prevention drugs, such as those that can be administered to people at risk for Alzheimer’s disease before symptoms appear. These drugs could prevent or delay the development of dementia symptoms.
A similar approach is used to prevent people who are HIV-positive from developing AIDS symptoms. These drugs represent a different approach from symptomatic drugs, which are intended to treat Alzheimer’s disease symptoms such as agitation, cognitive loss, hallucinations, or depression.
Several changes are required to maintain a diverse pipeline of preventive and symptomatic drugs, according to the analysis, which was reviewed by academic research experts and select RA2 members. These changes include a standing, high-performance clinical trial infrastructure that allows for rapid testing and fast failure or success.
In addition, the field needs robust biomarkers that help to indicate disease severity or progression and help to assess the effectiveness of drugs in populations without any symptoms, potentially preventing the development of symptoms altogether, according to the analysis. A greater understanding of biomarker research will assist researchers and clinicians to prescribe medicines to the appropriate populations.
New end points for trials are another necessary change, said the group. Many of the current scales used in Alzheimer’s disease trials will not be effective in people in early stages of the disease, since symptoms like cognitive decline may occur late in the disease.
Clinicians and researchers also should develop mechanisms for actively sharing information about which treatments work best with certain patient populations, according to the analysis.
Finally, the field requires innovative clinical trial designs to increase flexibility for drug developers. Such designs include adaptive trials that are modified based on patient outcomes, as well as trials of combinations of novel treatments. The latter trials could include drugs with demonstrated target engagement, but without efficacy as monotherapy.
Phase II/III and Phase III Drug Trials
Trials of several phase II/III drugs and one phase III drug will be completed in 2017. The phase II/III treatments include AC-1204, an oral drug intended for patients with mild to moderate Alzheimer’s disease that improves mitochondrial metabolism through chronic ketosis. A combination of albumin and immunoglobulin is being studied for patients with mild to moderate Alzheimer’s disease. It is an IV immunosuppressant with possible antiamyloid antibodies and albumin-binding capacity. Finally, a phase III trial of suvorexant, an oral orexin receptor antagonist under investigation for patients with Alzheimer’s disease and insomnia, will conclude in 2017.
“I am encouraged to see such a range of approaches to treating Alzheimer’s [disease] in phase II development,” said David Morgan, PhD, CEO of the Byrd Alzheimer Institute at the University of South Florida in Tampa. “There is much work that still needs to be done, but the drugs in phase II clinical trials offer a great deal of hope for the future,” he added.
—Erica Tricarico
Suggested Reading
Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014; 7(6):711-730.
Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8:39.