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Saturday, October 21, 2017 12:05:33 AM
1. A dose that was declared safe in a small trial of ~70 people proved unsafe in a larger ~ 400 person trial.
2. Who would have guessed the FDA would grant “fast track” as results didn’t seem particularly impressive. Perhaps a good sign for A2-73’s chances.
3. Notice how long the trial is taking even with Fast Track? Three years! And that’s for strictly a Phase 3 not a combined 2/3. They actually received fast track in 2013 so it’s been closer to 5 years to design and complete the Phase 3.
4. Perhaps “rates of hippocampal shrinking or CSF biomarker measures. “ are indicators that Anavex should be measuring?
5. Looks like this soon to be completed trial is not targeting A-beta either, maybe it can help lower that 99.6 rate?
“This compound was discovered by TransTech Pharma as TTP488 and licensed to Pfizer as PF-04494700. In 2005, Pfizer ran a 10-week Phase 2 trial in 67 people with mild to moderate AD. This trial compared two doses—15 mg for six days followed by daily dosing of 5 mg, and 60 mg for six days followed by daily dosing of 20 mg—against placebo for safety and tolerability. Both doses were reported to be safe and well-tolerated, with more people in the treatment groups completing the trial than people in the placebo group (Sabbagh et al., 2011).
In 2007, Pfizer and the National Institute on Aging jointly funded a larger, 18-month Phase 2 trial run via the Alzheimer's Disease Cooperative Study (ADCS). This trial recruited 399 people with mild to moderate AD and evaluated the same doses for safety and efficacy as measured by the ADAS-cog. The higher dose was dropped after a six-month interim analysis flagged both safety signals and faster deterioration. The low dose was halted before its intended conclusion following a futility analysis that indicated no benefit; however, follow-up examination conducted after treatment was suspended did suggest a possible belated clinical benefit for the low dose (see Nov 2011 conference news story).
Pfizer terminated its work with this compound in 2011. Pfizer had previously been developing PF-04494700 for diabetic neuropathy but discontinued this program as well.
In March 2013, TransTech Pharma announced in a press release that it had received fast-track designation from the Food and Drug Administration for this compound in Alzheimer's disease, and in July it announced that it had met with the FDA and was planning a pivotal trial in patients with mild to moderate AD.
In April 2015, a Phase 3 trial of azeliragon began at three sites in the United States and in Toronto. This study will compare an 18-month course of the 5 mg daily dose to placebo in 800 people who have a clinical diagnosis of mild probable Alzheimer's disease and an MRI consistent with this diagnosis. The trial does not use CSF or amyloid PET to ascertain that Alzheimer's underlies the clinical symptoms. The twin primary outcomes are the ADAS-cog and CDR-sum of boxes. The trial is set to run until 2018.
http://www.alzforum.org/therapeutics/azeliragon
“http://www.alzforum.org/news/conference-coverage/door-slams-rage
“Galasko’s presentation offered a glimmer of hope when he described results of a follow-up examination, conducted after treatment was suspended. That analysis hinted at a possible belated clinical benefit for a low dose of the study drug; however, that only became evident after most patients had already been taken off the treatment. Although far from conclusive, the findings may serve as a cautionary tale for adaptive-style trials that rely on interim analyses, said Galasko.”
“When Galasko and colleagues analyzed the complete dataset including all 18-month measurements, things got interesting (or confusing, depending on one’s point of view). They found that the rate of cognitive decline in the high-dose group had slowed down, and their ADAS-cog scores were now similar to those of the placebo group, at least for those patients who continued to return for follow-up visits. Galasko could not explain the faster cognitive worsening in this group or their subsequent stabilization of cognitive symptoms. “We don’t know the mechanism of toxicity. We did not find any evidence of vasogenic edema or any other abnormality on MRI,” he said.
When the researchers analyzed the results of the 69 patients in the lower-dose group who completed the 18-month analysis, they found post-hoc evidence of improvement in their ADAS-cog scores compared to the 68 patients in the placebo group. There were, however, no differences in other clinical outcome measures or in the rates of hippocampal shrinking or CSF biomarker measures. This improvement in ADAS-cog scores was not detected at the 12-month timepoint, and it disappeared if the researchers only analyzed test scores obtained from patients while they were receiving the study drug.
Although the clinical trial did not provide evidence to support continued development of PF-04494700, Galasko said ending the trial early may have prevented the scientists from seeing any positive effects that required more than 12 months to become apparent. “We need to be careful about adaptive designs and stopping rules if we want to get the maximum amount of information about a drug,” he said. Other researchers at the meeting pointed out that the findings are difficult to interpret, given that the trial was stopped early and so many patients dropped out. “
Recent AVXL News
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 08/06/2024 09:21:05 PM
- Anavex Life Sciences Reports Fiscal 2024 Third Quarter Financial Results and Provides Business Update • GlobeNewswire Inc. • 08/06/2024 11:30:00 AM
- Anavex Life Sciences to Announce Fiscal 2024 Third Quarter Financial Results on Tuesday, August 6, 2024 • GlobeNewswire Inc. • 08/01/2024 11:30:00 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 07/30/2024 09:20:53 PM
- Anavex Life Sciences Announces Translational Biomarker Data for ANAVEX®2-73 (blarcamesine) in Fragile X Syndrome (Major Cause of Autism) at the 19th NFXF International Fragile X Conference • GlobeNewswire Inc. • 07/30/2024 11:30:00 AM
- Form S-3 - Registration statement under Securities Act of 1933 • Edgar (US Regulatory) • 07/29/2024 09:21:49 PM
- Results from Anavex Life Sciences Landmark Phase IIb/III Trial of Blarcamesine Presented at Alzheimer's Association Conference • GlobeNewswire Inc. • 07/28/2024 09:00:00 PM
- Anavex Life Sciences to Present at the H.C. Wainwright 5th Annual Neuro Perspectives Virtual Conference • GlobeNewswire Inc. • 06/20/2024 11:30:00 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/17/2024 11:30:10 AM
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- Anavex Life Sciences to Present at the H.C. Wainwright 2nd BioConnect Investor Conference at NASDAQ • GlobeNewswire Inc. • 05/14/2024 11:30:00 AM
- Shareholders that lost money on Anavex Life Sciences Corporation(AVXL) Urged to Join Class Action - Contact The Gross Law Firm to Learn More • PR Newswire (US) • 05/10/2024 09:45:00 AM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 05/09/2024 08:35:55 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/09/2024 12:00:30 PM
- Anavex Life Sciences Reports Fiscal 2024 Second Quarter Financial Results and Provides Business Update • GlobeNewswire Inc. • 05/09/2024 11:30:00 AM
- The Gross Law Firm Announces the Filing of a Securities Class Action on Behalf of Anavex Life Sciences Corporation(AVXL) Shareholders • PR Newswire (US) • 05/07/2024 09:45:00 AM
- Form DEFA14A - Additional definitive proxy soliciting materials and Rule 14(a)(12) material • Edgar (US Regulatory) • 05/06/2024 10:03:33 AM
- Anavex Life Sciences Corporation Sued for Securities Law Violations - Contact The Gross Law Firm Before May 13, 2024 to Discuss Your Rights - AVXL • PR Newswire (US) • 05/03/2024 09:45:00 AM
- Anavex Life Sciences to Announce Fiscal 2024 Second Quarter Financial Results on Thursday, May 9th, 2024 • GlobeNewswire Inc. • 05/02/2024 11:30:00 AM
- May 13, 2024 Deadline: Contact The Gross Law Firm to Join Class Action Suit Against AVXL • PR Newswire (US) • 04/26/2024 09:45:00 AM
- Contact The Gross Law Firm by May 13, 2024 Deadline to Join Class Action Against Anavex Life Sciences Corporation(AVXL) • PR Newswire (US) • 04/19/2024 09:45:00 AM
- The Gross Law Firm Reminds Shareholders of a Lead Plaintiff Deadline of May 13, 2024 in Anavex Life Sciences Lawsuit - AVXL • PR Newswire (US) • 04/16/2024 09:45:00 AM
- Class Action Filed Against Anavex Life Sciences Corporation (AVXL) - May 13, 2024 Deadline to Join - Contact The Gross Law Firm • PR Newswire (US) • 04/12/2024 09:45:00 AM
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