Lilly And Its Alzheimer's Drug: Hope Or Hype?

Even if approved I would be surprised if the FDA allowed Lilly to use the term "Disease Modifying" without a long term survival study, which if shown to have a survival advantage over current therapies will have correctly shown that the drug will have actually identified one mechanism for the disease. Likewise even if the drug reduces beta amyloid but does not improve morbidity or mortality in a statistically significant way you cannot promote this compound as "Disease Modifying".

OII wrote: "Likewise even if the drug reduces beta amyloid but does not improve morbidity or mortality in a statistically significant way you cannot promote this compound as “Disease Modifying”."

Why not? Manufacturers of MS drugs all term them DMD's if they reduce lesion counts or relapses, even if patients continue to become more and more disabled while taking them.

Thanks. However, I believe that to the average patient the term "Disease Modifying" would be interpreted as "Disease Improving", although the term "modify", technically speaking could, go either way. I have no problem, for example with the DMARD'S since they actually improve symptoms, not here, or in the case of "disease modifiying" MS drugs that worsen the patient's condition. In such cases the term is more of a marketing hook than a clinically meaningful term.

When Lilly says something is safe, it's time to run for cover. Remember the internal documents from Zyprexa? Who knows what little, um , "details" from the clinical trials will eventually come out in the wash.

My understanding is that the term "disease modifying" is intended to indicate that the drug is aimed at the underlying pathological process, and is not just a claim of superior efficacy.

The cynical remarks about MS drugs above are in at least some cases misplaced. Tysabri and BG-12 among others have been shown not only to reduce "lesions or relapses" but also to slow the rate of disability progression.

http://www.ncbi.nlm.nih.gov/pubmed/16510744

http://www.ncbi.nlm.nih.gov/pubmed/22992073

It would be nice if we could stop this disease in its tracks, but drugs that reduce the rate of disability progression by nearly half deserve the term "disease modifying" in every sense.

Yes,John Tysabri will modify your MS by prematurely sending you to the vineyard.

My spell check meant to say boneyard.

You're certainly correct that Tysabri has killed some people OII. But in patients who lack known risk factors, the risk is less than 1 in 10,000 per year, which is a little less than your annual risk of dying in a car accident.

http://www.nejm.org/doi/full/10.1056/NEJMoa1107829

I have friends and acquaintances with aggressive MS. It's made a real difference in their lives. It's easy to p*ss on things, but in this case you should not.

"Disease modifying," which seems to be the tangent subject now, is not necessarily well clarified. Investigators, the FDA, and others have struggled with a good definition of the term. Generally it is understood to apply to a compound that addresses the (supposed) underlying pathology of the disease--in the case of Alzheimer's, amyloid build-up. For a compound to show disease-modifying benefits, it must have effects that go beyond mere symptomatic improvement (but/and the DM compound may not necessarily improve symptoms!). Disease modification can be difficult to demonstrate clinically, and it is the reason that biomarker outcomes are useful in cases of AD, MS, and rheumatoid arthritis.

What's concerning about the latest Lilly data is the (popular) focus on the relative risk difference between the solanezumab- and placebo-treated groups (~34%) as opposed to the absolute score difference, which was only 1 or 2 points.

My sister died from aggressive MS. All drugs failed. I'd tell you to go piss up a rope but as everyone knows I'm too much of a gentleman to even think that.

@John, well good for the people for whom it worked without killing them. That just means this designer molecule is NOT mass-market.

Once "an acceptable amount of deaths" is an unacceptable metric in drug development, we'll really get somewhere.

And one day this place that We the People had built with our labor taxes will be beat back into ploughshares from the sword it is now and be of service to providing for the sustainable life-maintenance needs of the human species - which includes CURES for the ever-present biological threats to the HUMAN SPECIES (virus, amoebas, bacteria) and not just catering to genetic defects that can easily be bred out of the population like was done without force over a thousand years ago in many northern EU tribes because they believed that knowingly sentencing a person to live in a defective body was not a sane way to live. Life is tough enough with good health and a normal mind.

http://www.wired.com/threatlevel/2012/03/ff_nsadatacenter/

only predators "spy", in the final analysis...

@oii - actually person who did last post in this thread

If you are "too much of a gentleman to even think that" - WHO ARE YOU and what have you done with / to the real oii??

OII, sorry for your loss. Did she try Tysabri and what was her experience?

Its worked well for people I know. I was in a business meeting the day that it was pulled off the market, and the VP I was talking to got a little teary eyed when I mentioned it, as the drug had stopped his wife's disease progression dead in its tracks.

DZ,"Acceptable number of deaths" for driving an automobile for a year is one in 8000. You take that risk in exchange for the convenience of not living within walking distance of your job and the grocery store. Likewise, the opportunity to avoid disability will be worth accepting a certain risk of death for many.

It would be nice if they did not have to make that choice, just as it would be nice if cars got 1000 mpg and did not generate greenhouse gases. We do what we can with the tools we have.

John, she died before Tysabri came out. Actually my resentments are misplaced. They should be squarely directed at the American Academy of Neurology, which persists in the ancient belief that MS is a pain-free disease when most patients with MS of any duration suffer pain, sometimnes intractable.

The "reason behind the reason" is they don't want to get in the business of pain management, and in fact, even though they are neurologists by training, most are remarkably ignorant, maybe even willfully ignorant on the appropriate use of pain medication. They are afraid of "creating addicts". As a result, many, including my sister had to spend extra time and money going to a pain specialist.

This is pure folly, and is why the profession of neurology has advanced little beyond eliciting the Babinski sign and carrying around little vials of hot and cold water in their little black bag along with their spare bow ties and butch wax.

Yup, we had a chronic pain issue in my family for several years too. I've got a few longstanding resentments of my own.

@John, I was taught to be polite to people with less brain power. Thanks for alerting me to your limitation by comparing car deaths to cures for biological diseases. I'll stop wasting my time.

Hopefully, you'll eventually end up in a position of no decision making power over the direction of medical research and the metrics that measure its success - something like car sales...

FDA makes value judgements all the time on "acceptable" numbers of deaths in an NDA. When there is an unmet medical need for a serious illness and a new drug comes along that might cut into the death rate then the risk/benefit equation always factors in what they consider to be an "acceptable" mortality rate as a tradeoff for whatever they judge to be an "acceptable" incremental survival benefit.

It's the bread and butter of their job. They make these decisions on a daily basis. That's why end-of-Phase II meetings are useful to get an idea first hand from the regulators on how far out on the risk curve they are willing to spot you so that you can have some idea of the "acceptability" of your safety profile before you spend millions of dollars on what may ultimately prove to be an unsafe drug.

The agency does this every day of the week, Basically how they earn their keep.

Well DZ, I've always been a little intellectually challenged. But I'd appreciate it if you'll bear with me and help me figure this one out.

I've spent a fair amount of time in the infectious diseases area, and can tell you with some confidence that pretty much every antibiotic on the market today has a one in 10,000 to one in 100,000 chance of causing death. I think you can say pretty much the same thing for every AIDS drug on the market, though the risk might be a little higher for these.

My simple minded thought would have been that these have an attractive risk/reward ratio, and belong on the market. But if no risk of death from a pharmaceutical is acceptable, we should pull all of these drugs off the market, right?

Sorry to take up your time, as you've pointed out, I'm a moron.

Nope, John. There is only one person I've come across recently as a genuine moron, and a drooling one at that. His name is Harry Reid.

Note that I'm being gratuitous to Joe Biden, affectionately modeled after that mythical New orlans soft shoe dancer- Mr Joe Bangles.

@John - you are ASS-U-Ming that there is no such thing as a cure that does not cause "x" amount of deaths. That's one heck of a McKinseyparachute-in-and-change-it-all management style mental masturbation session, but, unfortunately, it's not science.

May a drone fall out of the sky on your head - whoopsie, so a certain amount of drones do that...

Back to the post. It's Hype...