There is something to be gained from the wise lesson of patience and methodical timing placed over speed and brute force. Time has borne these fables/lessons out throughout the ages over and over.)

“all his talk” and very little snail paced action.

Gottlieb advocated a better use of digital tools for capturing and auditing information to disrupt what he called legacy approaches. “They can provide better oversight [and] lower development costs and open up more trial sites—and more providers and patients—to opportunities to participate in trials,” he said.
He suggested that overly long, overly complex trials can deter patient enrollment, exhaust investigators, push trials out of the community setting, and delay completion of studies so long that their “findings are no longer relevant. Overly restrictive exclusion criteria can also screen out patients with a prior history of health complications.”

Gottlieb advocated a better use of digital tools for capturing and auditing information to disrupt what he called legacy approaches. “They can provide better oversight [and] lower development costs and open up more trial sites—and more providers and patients—to opportunities to participate in trials,” he said.
He suggested that overly long, overly complex trials can deter patient enrollment, exhaust investigators, push trials out of the community setting, and delay completion of studies so long that their “findings are no longer relevant. Overly restrictive exclusion criteria can also screen out patients with a prior history of health complications.”

Gottlieb and the FDA have been active on the clinical trial regulatory front of late. He recently said the FDA was close to rolling out some specific policies aimed at reducing burdens on the conduct of clinical trials.

As the a drug is proved for multiple indications with the same MOA doesn't the burden of proof become less under new FDA protocols?

Within a year of approval Anavex could also be a major player, if not dominant, in the CNS and psychiatric space.

Understanding and overcoming barriers to early diagnosis
Studies show that cognitive impairment may remain unrecognized in 27% to 81% of affected patients in primary care.2 However, of these patients with cognitive impairment, 60% to 80% have Alzheimer’s disease.1
Low recognition of Alzheimer's disease may be caused by several barriers, including:
The time burden associated with testing and counseling2
Reluctance of patients and care partners to report signs or symptoms due to stigma around Alzheimer’s disease2
Lack of diagnostic resources4

DID YOU KNOW?
Right now, current treatments for Alzheimer’s disease treat only the symptoms and are indicated for patients with Alzheimer’s dementia. They do not modify the underlying pathology of Alzheimer’s disease and are not targeted towards earlier-stage patients.10
Presently, investigational therapies targeting amyloid beta and tau are being studied for Alzheimer’s disease.10

In its February 2018 draft guidance for industry, the U.S. Food and Drug Administration signaled a willingness to consider a slowing of cognitive decline alone as the basis for approval. At the 11th Clinical Trials on Alzheimer’s Disease conference, held October 24–27 in Barcelona, Spain, leaders in the field wrestled with how this new guideline might be put into play, and what cognitive tests might fit the agency’s bill.

It is not so clear, after all, whether stage 1 disease actually exists,

Aisen noted that the difference in decline is slight in preclinical disease, detectable over three years on a sensitive cognitive battery such as the PACC, and over six years on the CDR-SB. In other words, detecting this modest decline would require either long trials or even more sensitive cognitive measures.

FDA says it will accept cognitive measures alone as the basis for approval in stage 2. It also says a drug’s benefit must be robust and consistent across multiple domains, and that the application will be stronger if supported by biomarker evidence. Petersen suggested mining longitudinal data to identify other early impairments, such as mild neurobehavioral symptoms, that could strengthen the case for a clinical benefit. “Perhaps we could marry subtle behavioral features with tau pathology,” Petersen said.

So which test is best for preclinical disease? Hendrix said it depends what researchers want to measure. Some treatments, such as cognitive enhancers, might improve progressive and non-progressive aspects of cognition. In that case, the PACC might be good for evaluating efficacy. Interventions such as nutritional or lifestyle interventions might be expected to slow age-related decline as well as Alzheimer’s pathology, and the API-LOAD might be the best test to evaluate efficacy (Langbaum et al., 2014). For a therapy targeting a specific AD pathology, such as amyloid or tau, the APCC is likely to paint a clearer picture of its effects. “It comes down to figuring out what kind of change you have in an untreated population, and what aspects of that change you’re targeting with your treatment,” Hendrix told Alzforum.

But let’s see where this murine Alzheimer’s vaccine goes. (I won’t be buying any shares of any company that aims to take it to pharmacy shelves. The story is yet too flimsy for the diligence I require for my infrequent biotech equity investments. Anavex still has the better story, I think.)

Anavex 2-73, in great contrast, works at the extreme upstream stage of the disease, facilitating the proper folding of productive enzymes. With those, the waste proteins aren’t accumulated; healthful nerve function is preserved or restored.

I’ll go with the Anavex approach.

Now actively recruiting, the study (2017-004335-36) is expected to enroll approximately 120 Parkinson’s patients ages 50 or older with a dementia diagnosis. It is being conducted across several clinical sites in Spain, and has received the support of the Michael J. Fox Foundation for Parkinson’s Research and León Research.
Anavex has been developing Anavex 2-73 as a potential disease-modifying therapy for Alzheimer’s disease. It is a small molecule that activates the sigma-1 receptor located in a cellular structure called the endoplasmic reticulum, which is critical for several cellular regulatory mechanisms.
“We are very pleased to initiate our first patient enrollment into the Parkinson’s disease dementia Phase 2 study of Anavex 2-73,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release. “This is an important step toward achieving clinical data for the second indication initiating this year for Anavex 2-73 also incorporating genomic precision medicine biomarkers.”
Trial participants will be randomly assigned to receive orally 10 or 20 mg of Anavex 2-73 or a placebo for 14 weeks.
Researchers will evaluate the impact of the treatment on cognition, as determined by the cognitive drug research computerized assessment system, as well as on patients’ motor function and sleep quality.
During the study, researchers will also assess genomic precision medicine biomarkers associated with Anavex 2-73 that were identified in another Phase 2 trial (NCT02244541) in Alzheimer’s disease.
Additional information (in Spanish) on the trial can be found here. Patients and caregivers interested in taking part in the study can download and fill out a simple screening questionnaire that is available on the website to assist in discussions with their physician.
“Parkinson’s disease is an already prevalent disease among older individuals that is poised to become a much greater public health problem around the globe in the coming decades and is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes,” Jaime Kulisevsky, MD, PhD, principle investigator of the Phase 2 trial, as well as a professor at the Autonomous University of Barcelona and director of the Movement Disorders Unit of the Sant Pau Hospital in Barcelona.
Results from preclinical studies have shown that Anavex 2-73 has the potential to restore function to damaged nerve cells in mouse models of Parkinson’s disease. The compound was also found to target faulty proteins and poorly working mitochondria — the cells’ powerhouses — preventing oxidative stress and inflammation.

What would it take to gain conditional approval in Spain for PDD?

40 on low dose, 40 on high. If we see 20 patients improve in each dosing group in varying degrees, does that gain us conditional approval.

Will AI be able to look at all the biomarkers and results tweeking another bread crumb in the search for AD? And conversely will AI look at AD progression and pick up on shared similarities with PD, PDD, MS, Epilepsy?

It is a P2, double blinded with PM approach being tested and regardless of the potentially small incremental efficacy signal of the particular PM aspect still valid and clinically meaningful if stat sig.

[/qIt is criminal to have a drug that is safe and has helped people to be kept in a box. There appears to be no sense of urgency

Does that imply $AVXL could go up, down or sideways?

So far, I see nothing that suggest that 2-73 is a cure. What I see is that it is drug that stops or slows down the rate of decline for AD. That is HUGE advancement in the treatment of AD. It is not a cure.

Have not seen the word cure used to describe A2-73 around here in a long time. AVXL research-testing for me is a step and commitment to a learning process involving CNS diseases and likely more (no more-no less). It seemed to me that the "Amyloid thesis" came from researchers backing into an AD explanation when discussing post mortem results from people who had presented AD symptoms. We later see that same procedures done to others non AD people w/plaque-Tau-misfolded w/similar conditions were ignored by researchers or not explained. In other words no causality was shown while researchers kept ignoring these contradictions. Many papers-studies done to rationalize for "Amyloid Thesis" and an enormous amount of money and time was expended while all the while the contradictions were just dismissed as anecdotes until the cow went dry and Dr.G. called it. Even today there is no evidence of any process evaluation(post mortem) by the FDA asking how it was so wrong for so long. That whole school/process is/was fundamentally dishonest. The required massive trials w/placebo school of thinking is still dominant. I do not accept that smart people sat in rooms for decades and did not suspect they might be on the wrong path, AKA..worthless.

I am thankful Dr.M. has chosen alternative paths.