Top-line data announced this week from a Phase 2 clinical trial of the amyloid-β (Aβ) oligomer blocking drug scyllo-inositol (aka AZD-103, or ELND005) have given Elan Corporation PLC and partner Transition Therapeutics Inc. reason to take the compound into Phase 3. Overall, the drug did not significantly improve cognition and function in participants with mild to moderate Alzheimer disease. It therefore missed its formal co-primary outcome. Even so, the companies’ press release states that AZD-103 had an effect on clinical endpoints in an exploratory analysis. This suggested to the company scientists that a subgroup of patients may have improved on the medication. The compound achieved pre-determined target levels in the cerebrospinal fluid (CSF) and had effects on CSF Aβ, noted Transitions CEO Tony Cruz in a conference call to investors August 10. “Any changes in the biomarkers may be suggestive that the drug is affecting the underlying pathology,” Cruz said.

“I tend to be encouraged whenever an AD drug development project moves forward (despite the disappointing track record in pivotal trials),” said Paul Aisen, University of California, San Diego, who was not involved in the trial. “But, of course, we need to examine the specific findings of the Phase 2 study.”

One of several isomers of the cyclic sugar alcohol inositol, scyllo-inositol prevents formation of Aβ oligomers, which are believed to be the most toxic forms of the peptide. The inositol isomer appears to block phospholipids, such as phosphatidylinositol, from promoting Aβ oligomerization (see ARF related news story). Scyllo-inositol prevents accumulation of Aβ in the brains of mouse models and protects them from cognitive decline.

For this Phase 2 trial, a total of 351 participants with mild to moderate AD were given 250 mg, 1,000 mg, or 2,000 mg of the drug twice daily. The two top doses were subsequently dropped over safety concerns (see ARF related news story). The 250 mg dose appeared to have a favorable safety profile so far. According to Cruz, clinical significance was not expected in the trial because it was not sufficiently powered to detect such changes.

Nevertheless, given the safety profile of the 250 mg dose and the effects on CSF and on clinical outcomes in exploratory analysis, the companies, after consultation with “15-20 advisors and key opinion leaders in the field,” said Cruz, have decided to move forward into Phase 3. Alzforum readers may remember that the γ-secretase modulator flurizan also showed promising signs in Phase 2, only to fail in a subsequent Phase 3 trial (see ARF related news story). In that case, indications were that the drug failed to find its intended target, as it never reached levels in the CSF that came close to its effective concentration. Alzhemed, an Aβ aggregation inhibitor, also showed promising Phase 2 data, apparently reducing CSF Aβ in mild to moderate AD patients, but it, too, failed in Phase 3 (see ARF related news story). The field will be hoping for something better from scyllo-inositol.—Tom Fagan.


  1. These types of press releases and hyped reviews only give false hope to the public. The AD community should be more aware of the impact that such company-driven statements have on the families of those suffering from the disease.

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News Citations

  1. Aβ Busters and Other Ploys Show Promise for Treating Neurodegeneration
  2. Drug Brief—Adverse Events Prompt Dose Drop in Elan Trial
  3. Chicago: Flurizan Postmortem
  4. FDA Deems U.S. Alzhemed Trial Results Inconclusive

External Citations

  1. Elan Corporation PLC
  2. Transition Therapeutics Inc.
  3. companies’ press release

Further Reading