BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

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MadGirl
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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby MadGirl » Mon Feb 22, 2016 8:12 am

Exactly which drugs are in the pipeline that have been shown (or are assumed to) reduce beta amyloid more than Biogen's Aducanumab?
And what is the APP mutation?

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby J11 » Mon Feb 22, 2016 5:23 pm

Welcome aboard MadGirl!

There are a whole bunch of powerful BACE1 inhibitors that reduce amyloid levels by an overwhelming amount (some greater than 90%).
I am not totally sure whether I would even want my amyloid levels to be reduced by over 90%, it must be doing something useful.
Yet, those who go onto to develop dementia do not have a slight increase in amyloid levels: many of them are carrying more then 5 years of amyloid buildup!

http://www.alzforum.org/therapeutics/verubecestat

I think we have already reached the point of no return with verubecestat.
It simply no longer matters what top line results will be reported for these phase 3 trials.
Given the current evidence with the below APP variant, it can be seen that lowering
amyloid by 40% over a long period of time can have profound anti-dementing effects.
The FDA can do whatever it pleases, I think there will be a fair number of people who will be making friends
with some Chinese chemists if there is some sort of push back to making this a consumer medicine.

The market would be overwhelming.
The clinical dementia market would be tiny by comparison; they could play nice with the dementia community
simply to gain goodwill in the consumer market.

Let's see 100 million at risk Americans, charge them say $1000-$2000 per year... hmm that starts to add up to
some truly serious money.
Or, they could try it the dumb way 100 million at risk Americans, charge them say
$50,000 - $100,000 per year and now you're talking about who can you hit up to buy a round of coffee.

Monopolies do not maximize profit by maximizing price, profit is maximized at the production level where marginal revenue equals marginal cost. Pricing at such a point might not exactly maximize total welfare, though there would still be a whole lot of happy people.

These Mendelian randomization studies are more impressive than clinical trials, where
there can be a nearly endless list of confounders.

http://www.nature.com/nature/journal/v4 ... 11283.html

"Researchers found that the A allele of the APP variant (rs63750847-A) was significantly more common in a control group of patients who had lived to at least 85 years of age without a diagnosis of AD than in a group with AD (0.62% vs 0.13%; odds radio [OR], 5.29; P = 4.78 × 10-7), pointing to a protective effect against the disease.

Investigators confirmed the results by sequencing rs63750847-A in predicted carriers who were found to have the correct copy number, and by genotyping the allele in cases and controls.

The rs63750847-A variant occurs with greater frequency among the elderly. The authors estimate that the odds for carriers of this variant reaching age 85 are 1.47-fold the odds for noncarriers."

So reducing amyloid by 40% from normal levels (?) reduced AD risk by over 80%!
http://www.medscape.com/viewarticle/767403

Did someone say CRISPR? Oh, I thought I heard let's CRISPR it.
Hmm, I suppose the Nordic sperm bank with the 847-As should be doing a roaring business.
I mean why wait 200,000 for the most adaptive genes to win?

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby J11 » Thu Sep 01, 2016 10:27 am


Harrison
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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby Harrison » Thu Sep 01, 2016 2:48 pm

I think we are all watching this with keen interest. If things continue the way they are heading, with 43% of the 6mg dose and 55% of the 10mg dose showing brain swelling, I could see this not being approved for use in ApoE4 carriers.

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby MadGirl » Mon Sep 05, 2016 10:21 am

In the current phase 3 trial, APOE4 carriers are only eligible for the 6 mg/kg, 3 mg/kg or placebo……a sure sign that Biogen is only going to apply for FDA approval for the mid and lower dose for APOE4 carriers????

In the Phase 3, if ARIA-E occurs, then the drug is withdrawn until resolution is confirmed by MRI and then the participant is re-introduced to the drug at the next lowest dose.
The really good news here is that the numbers for the 3 mg/kg in the Phase 1b were pretty good. It appeared to slow the progression of ALZ, effectively cutting the speed of progression in half.
We'll certainly take that!!!
No one can explain yet why the 3 mg/kg performed better than the 6 mg/kg……something that everyone excepts is an anomaly based solely on the small size of the trial?? But given the latest research showing that beta-amyloid is the brain's innate immune system responding to a microbial assault, possibly gentle anti-amyloid therapy is the way to go!

My husband is participating in the Phase 3 trial and had ARIA-E. He was asymptomatic and it resolved in 4 weeks. He's a 3/4.
I am told that the next thing coming down the pike to watch for will be Biogen's BACE inhibitor and combining that therapy with Aducanumab anti-amyloid therapy.

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby J11 » Mon Sep 05, 2016 1:52 pm

Yes, that is interesting that the phase 1 trial included MMSEs down to 20 while the new phase 3 only includes those down to 24. They are also including those with an MMSE of 30, so we are starting to move beyond clinical AD to MCI. This would greatly expand Biogen's market potential while at the same time limiting dosing and side effects.

I will be very very interested to see what their pricing strategy will be. If they price it similar to cholesterol drugs then they will have a large pre-clinical market that will use it as a lifestyle drug. However, if they
price it like many cancer drugs at tens of thousands or more dollars per year then the lifestyle market will disappear. Where they finally decide to price it will be of substantial importance to many on the forum.
If Biogen intends to be a profit maximizer, then it must remember that even with a monopoly, profit maximization does not occur at price maximization.

Aducanumab gives me a good feeling. This is not a drug dreamed up in a lab. The drug was actually sourced from people who lived to advanced age without dementia. In a sense it has already been shown in people to be safe and effective. The only question is what happens when the dosing is greatly increased to be a pharmaceutical.

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby SusanJ » Mon Sep 05, 2016 3:03 pm

Madgirl, best wishes for phase 3 with your hubs. Let us know how it goes!

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby J11 » Mon Sep 05, 2016 3:06 pm

MadGirl, what is your husband's MMSE score?

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby MadGirl » Mon Oct 10, 2016 8:09 am

Hi All,
Sorry for disappearing for a while. Issues with my 89 1/2 year old Mom.

First of all, Aducanumab does not stop the progession. It is only supposed to slow it down. My husband has declined while doing the trial.....I have noticed that his memory is slightly worse and that he does need more prompting than he did when he was diagnosed last December.
I do not know his official MMSE score on the day when he applied for the trial last January. I think it was somewhere between a 24 and 27, but I will find out. As for participating with a 30, I do know that they were looking hard at something called RBANS (I think) and you are not eligible for the trial if your score on that is too high....you have to have demonstrated memory deficits. There is a lot riding on this trial and they are screening very carefully - you have to have alzheimers as confirmed by a beta-amyloid pet and you have to be having enough memory issues that you WILL decline over the course of the trial, but you cannot be too far down the Alzheimer's road because they've figured out through other MAB trials that it only works if you take if early in the disease.

Update on my husband:
He started the trial last February. Everything was going well until after his 6th infusion, he had asymptomatic ARIA-e that was described as severe.
30 days later we were told that the MRI showed no signs of the swelling. So he missed one infusion in July and had his 7th infusion on schedule in August. At that time the protocol stipulated that he resume infusions on the next lowest dose.
His MRI two weeks after the 7th infusion showed severe ARIA-E for the second time. Here is where we are now.
If some mistake was made either by the imaging center sending the wrong MRI in August showing that the swelling had resolved OR by the pharmacist giving him the wrong (the same 6mg/kg) dose of the drug for the 7th infusion - we'll never know. It is what it is.
By process of elimination I am 99% sure that he was originally on the 6mg/kg dose originally and was then reduced to the 3 mg/kg and now I am told the protocol mandates that he be reduced again - this time he will be placed on placebo.

We are heartbroken of course. And now trying to regroup and figure out where we go from here. Any advice on trials would be most appreciated!!!
The neurologist says that most trials say you must be off of an anti-amyloid vaccine for 6 months - February 18th is 6 months from the 7th infusion. And some trials say you can't have had any cancer for 5 years - he had a melanoma in February of 2012, so February 2017 is it!

One idea is to stay on the trial in hopes of getting on the open label extended trial next July or August, and I am trying to find out what the qualifications and exclusions for that are. He could start on Aricept and use that for the next 10 months to delay progression since one exclusion is having your MMSE decline too much, I think. However, after 6 months of the infusion on the extension he may have the same thing happen again.

There are the BACE inhibitor trials going on. It's a pill and not so much in terms of side effects.

There is a Phase I stem cell trial beginning at University of Miami - not sure if they would let him in after doing the Biogen trial. It's one infusion/injection of stem cells and they follow you for a year. High dose, low dose or placebo.

Another interesting and exciting and maybe scary thing is that Nilotinib trial out of Georgetown. You guys should look at that one! Michael J. Fox and Georgetown got into a flap over control/design of this one and Georgetown is proceeding on their own and the FDA approved including Alzheimer's patients in this new Phase II trial. It is scary because it's a lower dose of a chemotherapy drug. And my research is saying that you need to stay away from CYP34a inhibitors when taking this drug - some of the Bredesen herbal stuff may fall into that category. Chemo drugs scare me and I wouldn't want to let him take anything else that impacts it.

Thoughts???

We have his first annual checkup at Mayo in Rochester with a top Alz doc and researcher in 3 weeks. I want to collect all the info I can between now and then and discuss with him.

NOTE on trial protocol........they updated the trial protocol in September so that if you are already on the low dose of Aducanumab and have ARIA-e, you can continue on the low dose of the active drug rather than going on placebo. But that's only for the first incidence of ARIA-e. I am told my husband's case got the attention of the highest levels of the trial (some consolation - HA) and the determination was made that after the second incidence of ARIA-e you have to go to the next lowest dose, meaning that if you were already on the low dose then you drop down to placebo. :(

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Re: BIOGEN IDEC PRESENTS POSITIVE INTERIM RESULTS

Postby SusanJ » Mon Oct 10, 2016 8:56 am

Madgirl, so sorry to hear about the side effects. How frustrating.

I feel the best course is where you're going, your appointment with the Mayo doc. It will be critical for you to get expert advice on the options, which are certainly way out of my knowledge base or comfort level.

Hugs.


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