Elan, Wyeth Take an Inside-Out Approach to Alzheimer's Vaccine

The long-running saga of Elan's (ELN) attempt to come up with a vaccine for Alzheimer's disease continues. There have been bold attempts, setbacks, rethinks, more setbacks, and now they're starting up again. Dosing of the latest version of their vaccine against the beta-amyloid protein, known as ACC-001, was suddenly halted in April when one patient came down with a skin lesion which was thought to be possibly autoimmune-linked vasculitis.

Biopsy results didn't confirm that, though, and the Elan/Wyeth (WYE) partnership is resuming clinical studies. I'm not sure what that couple of months has done to their trial design; I assume that they've just started enrolling new patients and will continue with them, while continuing to monitor the former dosage groups. Maybe, though, there's a way to continue with some of those people and not lose all the time, effort, and data.

The idea of an amyloid vaccine has always excited and alarmed me in equal measure. But that's how I feel about the immune system in general, come to think of it. We have enough cellular firepower to completely destroy ourselves from the inside out - keeping that on a leash to where it (mostly) only goes after what it's supposed to is extremely impressive.

Now, I think that the usual sorts of vaccines are one of the great public health advances of civilization, but they work so well because they're targeted to outside agents (viral coat proteins and the like). Even so, there's a disturbingly large part of the population that remain suspicious of all vaccinations - I say "disturbing" not least because if that population gets too large, the efficacy of vaccination in general could be crippled. But what will these people think about a vaccine that's targeted to an endogenous protein? My immunology may need brushing up, but I can't think of any other example of such.

One thing that may keep this from becoming a huge issue, though, is that an amyloid vaccine, if it succeeds, will be targeted at the elderly rather than at children. And it'll be something that will have an effect against a disease that everyone can see right in front of them, rather than preventing diseases that most people have only read about in books. We'll be back at the situation that prevailed when the polio vaccine was introduced: no one had much doubt that the vaccine was better than the disease.

But even a vaccine fan like me still has room to admire, from a distance, the nerve of this approach. The brain is a special case, immunologically, and letting slip the dogs of war in there is not an intrinsically safe idea. But Alzheimer's is an intrinsically nasty disease...

Comments

[delta 777:]

again, Here Derek seems to share a common confusion with respect to Elan's Alzheimer's pipeline....Right now their prime focus is on an antibody (not a vaccine) therapy identified as AAB-001 (Bapineuzimab), which anticipates important PII result announcement very soon, and full PII info at ICAD on July 30..PIII for AAB-001 has already started... Although AAB-001 is an immunologic approach, it is distinctly different and not to be confused with ACC-001 which is an antigen, or vaccine.. Elan has several other extremely promising Alzheimer's drugs in its pipeline, as well as the highly effective multiple sclerosis drug Tysabri....Elan is primarily a research biotech, and commonly partners with companies better equipped for large scale manufacturing. (which arrangementsd also, because of careful poison pill agreements, protect against easy hostile take-over)....There is a very active InvestorVillage message board with quite a few brilliant and very knowledgeable posters on Elan (significant posts can be roughly presorted based based on number of recs, then following the thread): www.investorvillage.co...

2008 Jun 15 02:01 PM

[wilj:]

I don't see where you get the confusion part. Elan is indeed working on an active vaccine, called ACC-001, and I think Derek's concerns are quite warranted. The fact that they are also, even primarily, working on a 'passive' vaccination molecule (bapineuzumab) doesn't change the fact that the 'active' vaccination strategy has been a rocky ride and seems inherently more dangerous.

2008 Jun 15 10:37 PM

[jarcom:]

An alzheimer vacine....simply panovian. AHP used to be smarter than to go for such stuff.

2008 Jun 15 10:52 PM

[Laura P:]

My humble opinion: Immunotherapies in the brain are dangerous and can go wrong, wrong, wrong. That being said, passive immunization (antibody administration-- AB-001) is much better than active immunization (eliciting a response to an antigen-- AN-1792 and ACC-001).

The brain, as I'm sure you know, is an "immuno-privileged" site-- that is, normally immune cells never enter the brain unless explicitly instructed to do so (e.g. with a vaccine). Leukocytes are not "trained" not to react to brain antigens they way they are with almost every other antigen in the body so the brain doesn't become the accidental target of damaging inflammation. Any sort of vaccine could induce that vaccination-- ACN-1792 was stopped in its tracks in pIIa because of that very inflammation problem.

Elan is all excited because, even though their active vaccination didn't show much in the way of cognitive improvement, iautopsies of dead patients pII trials showed plaque regression. However, replacing one neurological disease with another isn't ideal and would probably only be OK'd for extreme cases. I am unimpressed.

The passive vaccination (AB-001) is safer, and indeed it seems to work better (even though in my opinion it's still risky). Nonetheless, passive immunization is not nearly as sexy as an active immunization that could work prophylactically to cure Alzheimers like we cured Polio. The word "vaccine" has people all excited when perhaps they shouldn't be.

Even passive immunization to beta-amyloid, though, vaguely misses the mark. It doesn't nip the problem in the bud. A secretase inhibitor-- something in Elan's pipeline-- would be able to nip the problem in the bud. However, it's years and years away...

I'm intrigued and think that perhaps I will write up a full review of immunotherapies for Alzheimer disease... bestofbiotech.wordpres...

2008 Jun 15 11:36 PM

[Laura P:]

* "Any sort of vaccine could induce that vaccination-- ACN-1792 was stopped in its tracks in pIIa because of that very inflammation problem."

Replace "vaccination" with "inflammation." My bad.

2008 Jun 15 11:43 PM

[delta 777:]

jarcom--you say "An alzheimer vacine....simply panovian. AHP used to be smarter than to go for such stuff."-----are you perhaps suggesting that AHP was "smarter" in its fen/phen days????

2008 Jun 15 11:54 PM