[johnt]

The results of the Cogane trial have been reported:

StockMarketWire.com - Phytopharm said no statistically significant effects or trends towards improvement were seen in the results from Phase II tests of early-stage Parkinson's suffers with its Cogane drug.

John

[Bob Dawson]

FEB 18 2013 PHYTOPHARM SHARE PRICE DROPPED 87% in early morning trading…

Professor C Warren Olanow, Professor of Neurology and Neuroscience at Mount Sinai Medical School and Co-chief Investigator for the study commented:

“This is disappointing news for the Parkinson disease community… The company is to be congratulated for carrying out this important study in such a high quality manner. Sadly, the results are negative.”

Commenting on these results, Tim Sharpington, CEO said: “We are naturally disappointed with the outcome of this study of Cogane™ in patients with Parkinson’s disease. Cogane had demonstrated encouraging efficacy in a wide range of industry standard pre-clinical models but this promise has not translated into clinically meaningful efficacy in this study. I would like to thank the investigators who conducted the trial, our collaborators and especially the patients who participated in the study…”

Analyst Dr Paul Cuddon at Peel Hunt said:
… “the result was a conclusive failure for Phytopharm's key asset”, and he attributed no value to the group's remaining pipeline of drugs.

“The comprehensive nature of the failure raises questions over the relevance of the pre-clinical models used, and the size/expense of the trial that was required to prove that Cogane was futile. Ultimately this outcome should have been reached at a lesser loss ,...”

“Reaching this point sooner remains a key challenge for the pharmaceutical industry. Until companies are better able to select for specific genetically defined patients for targeted drugs, UK pre-revenue drug development companies will remain a lottery. “

[Bob Dawson]

Then he went
to the window
and put his fingers
against the glass
and bowed his head
and cried

[Conductor71]

Originally Posted by Bob Dawson

[B]

Analyst Dr Paul Cuddon at Peel Hunt said:
… “the result was a conclusive failure for Phytopharm's key asset”, and he attributed no value to the group's remaining pipeline of drugs.

“The comprehensive nature of the failure raises questions over the relevance of the pre-clinical models used, and the size/expense of the trial that was required to prove that Cogane was futile. Ultimately this outcome should have been reached at a lesser loss ,...”

“Reaching this point sooner remains a key challenge for the pharmaceutical industry. Until companies are better able to select for specific genetically defined patients for targeted drugs, UK pre-revenue drug development companies will remain a lottery. “

Thanks, Bob. These quotes actually offer some hope, I think.

I do not think for a minute that this failed on a molecular level; GDNF and BDNF have proven twice now in other studies to be beneficial in PD patients. The key difference is delivery. This I think is more likely the cause for failure.

In the Amgen and Ceregene protocol, the neurotrophic was delivered directly to the brain. Cogane boldly chose to go with oral administration either with a liquid or pill. Have they heard nothing of the blood brain barrier? This is precisely why levodopa is so problematic. In essence they have taken a very viable substance for our treatment and delivered it with the most primitive form of delivery known to human kind: swallowing.

Why the shock and surprise over it's failure? It looks like Phytopharm knows that GDNF works but wanted to out shine delivery by making it more patient friendly.

My other thought is maybe de novo (pre drug) patients were not sufficiently brain damaged enough to distinguish the treatment from placebo. Amgen and Ceregene both included more advanced patients. Maybe the practice of relying on very early stage PWP to enhance end points has backfired?

In my opinion, neurotrophics themselves need to pass phase 3 to prove viable as treatment in general; then refine the delivery. They essentially put a faulty delivery system on trial and it failed, not the content. My concern is that investors won't see that difference and we may lose backing for neurotrophics in general.

My comments are based on quotes; I don't know all the specifics so maybe there is more to the story...

Laura

[soccertese]

http://www.independent.co.uk/news/bu...l-1802776.html

seems a little fishy to me.

[reverett123]

Originally Posted by soccertese

http://frugivoremag.com/2011/10/no-s...odia-all-hype/

seems a little fishy to me.

Olanow is a "big dog" who turns up in some interesting places. For one thing, he is purportedly the most published neuro in the US. He is also the neuro who was testifying as an expert for South African manganese mining companies against their workers last year as to whether the mineral could be blamed for the clusters of PD that were showing up. Mother Jones magazine reported that the good doctor ended up looking the fool when the judge got so disgusted that he ordered all parties to disclose every dime that had passed through their hands related to any other party involved. It seemed that Dr. Olanow had forgotten about three million dollars in consult fees paid by the mining corps to shells controlled by Olanow! Imagine his embarassment!

Olanow has another interesting feature. He heads up the group of multi-national neurologists who managed to secure a patent on the use of Mucuna for the treatment of PD! Never mind the fact that those uses have been known for millenia and that patents are to be granted for new ways of doing things. He and his buddies hold the key to any research to be done on the use of mucuna pruriens for PD virtually anywhere on the planet. Judging from the slim data flow (it has been ten years since the patent) the necessary permissions must be horribly expensive. Or totally non-attainable.

You gotta worry about the future of cogane. Will it be bundled with the remaining assets and sold fr a pittance to GSK? Or some new shell headed up by Olanow and associates? Never to be seen again? Or at least not until certain key patents expire?

[reverett123]

....the thread on Cogane, GDNF, and Kudzu

[ElBarto]

Phytopharm didn't exactly choose to deliver BDNF and GDNF orally with Cogane, as Cogane is neither - it's a plant-based substance that was purported to be small molecule, bioavailable substance that raised levels of those substances when reaching the brain. They started with something that was available orally, and didn't ignore a possible delivery advantage to pursue direct injection into the brain.

Yes, this study delivered Cogane as a liquid, and Phytopharm was looking for partners to develop a capsule, pill, or tablet, but in my opinion, the failure here is not in the phase II results, but maybe in the basic premise:

If Cogane is a small molecule that readily crosses the blood-brain barrier, as was reported, and dramatically raises the levels of neurotrophics once there, it would scarcely matter that it has now failed to prove beneficial in Huntington's and Parkinson's. Just having those properties would make it unusual, and full of promise to some group.

I suspect that premise is untrue, and that bothers me - if the rat and monkey studies were suspect, I would have liked to see the scientific community raise concerns, and I saw none.

I do however, take issue with the idea that denovo patients are any less likely to tell a placebo from a pill. I was de novo, and am still unmedicated, but since I was diagnosed 2.5 years ago, I suppose that I am no longer so "novo".... it doesn't make me any smarter than treated patients, but I know that when I have symptoms, it's the disease, not a side effect.

I know that exercise, reduced stress, and good diet all help, but that nothing makes the next day tolerable like a sound night's sleep. I would certainly have been subject to a placebo effect had I been in this study (I was disqualified upon screening, one number on my blood test indicates a liver enzyme slightly outside of acceptable tolerance) but I'd like to think that a neurologist recording 1's and 2's would be less easily swayed.

Originally Posted by Conductor71

Thanks, Bob. These quotes actually offer some hope, I think.

I do not think for a minute that this failed on a molecular level; GDNF and BDNF have proven twice now in other studies to be beneficial in PD patients. The key difference is delivery. This I think is more likely the cause for failure.

In the Amgen and Ceregene protocol, the neurotrophic was delivered directly to the brain. Cogane boldly chose to go with oral administration either with a liquid or pill. Have they heard nothing of the blood brain barrier? This is precisely why levodopa is so problematic. In essence they have taken a very viable substance for our treatment and delivered it with the most primitive form of delivery known to human kind: swallowing.

Why the shock and surprise over it's failure? It looks like Phytopharm knows that GDNF works but wanted to out shine delivery by making it more patient friendly.

My other thought is maybe de novo (pre drug) patients were not sufficiently brain damaged enough to distinguish the treatment from placebo. Amgen and Ceregene both included more advanced patients. Maybe the practice of relying on very early stage PWP to enhance end points has backfired?

In my opinion, neurotrophics themselves need to pass phase 3 to prove viable as treatment in general; then refine the delivery. They essentially put a faulty delivery system on trial and it failed, not the content. My concern is that investors won't see that difference and we may lose backing for neurotrophics in general.

My comments are based on quotes; I don't know all the specifics so maybe there is more to the story...

Laura

[johnt]

ElBarto,

Welcome to the forum. Keep posting!

The question of whether the placebo effect varies according to the severity of the disease and/or the medication is an interesting one.

My initial reaction is that the person with minimal symptoms has less to gain from the placebo. (If it were constant, a person with minimal PD would be able to "beat" a healthy person.) I find, 8 years in, that following a dose of, in my case, Stalevo the transition from "off" to "on" gets shorter.

One thing that will affect the outcome is the metric used. I understand the Cogane trial used UPDRS II/III. Did this have enough sensitivity to detect the probably small differences in this case? And was the scale linear enough to detect the contributions made by the placebo and the drug?

For instance, suppose our measuring scale had just two weights: 10kg and 30kg. And suppose the placebo effect was 10kg and the drug effect was 15kg. Given just the 10 and 30kg weights we couldn't differentiate between placebo and drug: both could lift the 10kg, but neither the 30kg.

John