If you have been following the somewhat dismal Alzheimer's disease clinical trial results you may also be a little curious about a recent uptick in positivity surrounding the upcoming Alzheimer's Association International Conference (AAIC). Thank you to friend Stuart for snapping the photo!
The experimental drug, solanezumab, an injectable humanized monoclonal IgG1 antibody directed against Aβ peptides, is garnering a lot of attention for it's potential disease modifying effects for patients at risk of Alzheimer's disease. Current treatments may modify symptoms associated with the disorder but none are approved for actual disease modification or delayed on-set of symptoms. Previous clinical trials reported negative results and seemed to doom the drug and similar formulations. Now there may be interesting clinical trial results being released at the upcoming July conference.
So what gives?
The experimental drug, solanezumab, an injectable humanized monoclonal IgG1 antibody directed against Aβ peptides, is garnering a lot of attention for it's potential disease modifying effects for patients at risk of Alzheimer's disease. Current treatments may modify symptoms associated with the disorder but none are approved for actual disease modification or delayed on-set of symptoms. Previous clinical trials reported negative results and seemed to doom the drug and similar formulations. Now there may be interesting clinical trial results being released at the upcoming July conference.
So what gives?
| A quick google search reveals the interest from news and finance channels. As estimates in Alzheimer's and dementia healthcare costs are quoted in excess of 600 billion dollars a year the enthusiasm is anticipated if not perhaps a little premature.  | CNBC... June 12 (Reuters) - The Alzheimer's Association may not offer an early look at highly sought clinical trial data on an experimental drug from Eli Lilly and Co after news of the impending release led to a jump in the company's shares. |
Let's look at what might be going on here. Full disclosure I do not have any insights or embargoed information, just a natural curiosity and a penchant for a bit of research. There is also a slight chance of over-simplification but I wanted to make the information relevant for many. Just a quick update--Doody and colleagues reported negative research findings in January of 2014 New England Journal of Medicine Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer’s Disease.
Hong Liu-Seifert from Eli Lilly and colleagues seem to be taking a fresh look at some of the original data and have recently used delayed-start design to model Phase 3 clinical trial solanezumab results as described in this open-access article, A Novel Approach to Delayed-Start Analyses for Demonstrating Disease-Modifying Effects in Alzheimer’s Disease.
The rationale of a delayed-start design is that under the null hypothesis, when the active drug has a purely symptomatic effect and has no effect on neuropathologic process, a delay in administration should have no lasting effect on patients. Thus the delayed-start patients are ex- pected to catch up to early-start patients (Fig. 1b). However, if the effect were not purely symptomatic and had altered the underlying progression, the delayed-start patients could not possibly overcome the losses sustained during the delay period (Fig. 1a). In other words, if the delayed-start patients do not “catch up” with the early-start patients (that is, the outcome for the delayed-start patients does not become similar in magnitude to that of the early-start patients), a conclusion can be drawn that the treatment is not purely symptomatic and has modified the underlying course of the disease, representing a disease-modifying effect. Such finding includes the possibility that the drug may have both symptomatic and disease-modifying effects. Demonstrating a disease-modifying effect would imply a sustained benefit of starting such drugs early.
Hypothetical modeling...
Modeling applied to Phase 3 solanezumab data in patients with mild to moderate AD
| What is visible from the graphic below--the phase 3 solanezumab data sustains the difference between the mean change in the "early start" and "delayed start" cohorts. An interesting finding worthy of anticipating the latest results from the EXPEDITION safety and efficacy studies and other data sets attempting to differentiate between potential disease modifying effects and attenuation of symptoms. |  Application to Phase 3 Randomized Clinical Trial Data We applied the analytical methodologies we propose in this paper to data from patients with mild AD in Phase 3 studies for solanezumab, a humanized monoclonal antibody, for the treat- ment of AD. EXPEDITION and EXPEDITION2 (ClinicalTrials.gov numbers NCT00905372 and NCT00904683) were Phase 3, 18-month, placebo-controlled studies investigating the efficacy and safety of solanezumab in patients with mild to moderate AD. |
The extension trial, EXPEDITION-EXT (ClinicalTrials.gov Identifier: NCT01127633) and the EXPEDITION3 on the progression of mild Alzheimer's disease patients (ClinicalTrials.gov Identifier: NCT01900665) are ongoing.
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